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ACOG PRACTICE BULLETIN

CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN­GYNECOLOGISTS NUMBER 67, OCTOBER 2005

(Replaces Practice Bulletin Number 26, April 2001)

This Practice Bulletin was developed by the ACOG Committee on Practice Bulletins-- Gynecology with the assistance of Mitchell D. Creinin, MD. The information is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.

Medical Management of Abortion

Over the past two decades, medical methods of abortion have been developed throughout the world and are now used in the United States. Medical abortion, which involves the use of medications to induce an abortion rather than a surgical abortion, is an option for women who wish to terminate a pregnancy up to 63 days of gestation (calculated from the first day of the last menstrual period). Medical abortions currently account for 6% of all abortions in the United States (1). The purpose of this document is to present evidence of the effectiveness, benefits, and risks of medical abortion and provide a framework for the evaluation and counseling of women who are considering medical abortion.

Background

Medications Currently Used in Medical Abortion

Mifepristone

Mifepristone (RU-486), a derivative of norethindrone, binds to the progesterone receptor with an affinity greater than progesterone but does not activate the receptor, thereby acting as an antiprogestin (2). Mifepristone's known actions on a pregnant uterus include necrotizing the decidua, softening the cervix, and increasing both uterine contractility and prostaglandin sensitivity (3, 4). Human studies have suggested that uterine contractility does not increase until 24­36 hours after mifepristone administration (4). At this point, the myometrium is five times more sensitive to the stimulatory effects of exogenous prostaglandins (4). Administration of mifepristone followed by a prostaglandin analogue, usually misoprostol, is the most commonly used medical abortion regimen throughout the world. As a progesterone receptor antagonist, mifepristone also has several other potential medical applications, including emergency contraception, cervical ripening for labor induction, and treatment of conditions

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such as symptomatic leiomyomata uteri, endometriosis, Cushing's syndrome, breast cancer, and glaucoma.

Misoprostol

Misoprostol is an inexpensive prostaglandin analogue in a tablet form that is stable at room temperature. Misoprostol is used clinically for prevention of gastric ulcers in individuals taking antiinflammatory drugs on a long-term basis, for abortion, and for labor induction. Pharmacokinetic evaluation of oral and vaginal administration of misoprostol demonstrates that oral misoprostol is absorbed more rapidly, resulting in a higher peak serum level (5, 6), but vaginal administration results in greater uterine contractility. Recent evaluations of sublingual administration show higher peak serum concentrations (7, 8), which may result in more unnecessary side effects (7). Further study of buccal administration may be warranted because its pharmacokinetic profile appears to be similar to vaginal administration (7).

nation do not confirm expulsion, ultrasonography is performed. If a gestational sac is seen, aspiration is typically performed. Efficacy with this regimen is approximately 92% in women with pregnancies up to 49 days of gestation (11, 12). Complete abortion rates are higher with earlier gestations: approximately 96­98% for pregnancies up to 42 days of gestation (13, 14), 91­95% from 43 to 49 days of gestation (13, 14), and less than 85% beyond 49 days of gestation (11, 13, 14).

Alternative Regimens

Other evidence-based medical abortion regimens have been developed in an effort to reduce side effects and to make medical abortion less expensive, safer, and more rapid. Regimens using 200-mg doses of mifepristone orally have efficacy rates comparable to the FDAapproved regimen (12, 15) at one third of the cost. Additionally, increasing the misoprostol dose to 800 µg and administering the medication vaginally decreases the time to expulsion (16), results in fewer side effects (16, 17), and improves complete abortion rates when compared with oral administration of a 400-µg dose of misoprostol (16, 18­20). Multiple large studies in the United States have demonstrated that a patient can safely and effectively self-administer the misoprostol (orally or vaginally) in her home (18, 19, 21­27). Investigations also have demonstrated the flexibility in timing between the two medications. One study demonstrated that 800 µg of misoprostol may be administered either 24, 48, or 72 hours after 200 mg of mifepristone with equal efficacy in pregnancies up to 56 days of gestation (23); a follow-up study using a regimen with a 24-hour interval between medications yielded similar results in pregnancies up to 63 days of gestation (24). Moreover, the results of a randomized multicenter study indicated that 800 µg of misoprostol administered vaginally 6­8 hours after 200 mg of mifepristone resulted in significantly fewer side effects (and no decrease in efficacy) than regimens using a 24-hour interval (27). Compared with the FDA-approved regimen, mifepristone­misoprostol regimens using mifepristone, 200 mg orally, and misoprostol, 800 µg vaginally, are associated with a decreased rate of continuing pregnancies, decreased time to expulsion, fewer side effects, improved complete abortion rates, and lower cost for women with pregnancies up to 63 days of gestation based on LMP.

Other Agents

Methotrexate is used less often today for medical abortion because of the greater availability of mifepristone. Methotrexate blocks dihydrofolate reductase, an enzyme involved in producing thymidine during DNA synthesis. Methotrexate exerts its action primarily on the cytotrophoblast rather than the developing embryo. Methotrexate has been used for more than 40 years to treat neoplastic diseases, rheumatoid arthritis, and psoriasis; other medical applications include treatment of systemic lupus erythematosus, dermatomyositis, severe asthma, Crohn's disease, and extrauterine pregnancy. Tamoxifen has been used in combination with misoprostol in some studies of early abortion. However, randomized trials have demonstrated no benefit of using a tamoxifen­misoprostol regimen compared with a methotrexate­misoprostol regimen (9) or misoprostol alone (10).

Mifepristone Regimens

Protocol Approved by the U.S. Food and Drug Administration

Mifepristone regimens vary according to dosage, timing, and route of administration (see Table 1). The U.S. Food and Drug Administration (FDA) approved the protocol of mifepristone, 600 mg orally, followed approximately 48 hours later by misoprostol, 400 µg orally. This is safe and effective for medical abortion through 49 days of gestation (calculated from the first day of the last menstrual period [LMP]). A follow-up evaluation is scheduled approximately 14 days after administration of mifepristone. At that time, if clinical history and physical exami-

Nonmifepristone Regimens

Methotrexate and Misoprostol

The combination of methotrexate and misoprostol is an alternative early medical abortion regimen. Among

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Table 1. Comparison of Common Medical Abortion Regimens

Common Regimens Mifepristone, 600 mg orally + misoprostol, 400 µg orally (FDA-approved regimen) Mifepristone, 200 mg orally + misoprostol, 800 µg vaginally (alternative evidencebased regimen) Overall Success Rate (%) 92a 95­99b­f Advantages and Disadvantages Must remain in office or clinic 4 hours after administration Compared with FDA-approved regimen: · More effective · Less time to expulsion · Fewer side effects · Requires vaginal administration of a medication Compared with mifepristone­misoprostol regimen: · Takes longer for expulsion in 20­30% of women · Readily available medications · Low drug cost · Requires complicated dosing regimens · Significantly higher incidence of side effects than other regimens · Low drug cost Gestational Age Up to 49 days Up to 63 days

Methotrexate, 50 mg/m2 IM or 50 mg vaginally, + misoprostol, 800 µg vaginally 3­7 days later

92­96g­i

Up to 49 days

Misoprostol only, 800 µg vaginally repeated for up to three doses

88j

Up to 56 days

Abbreviations: FDA, U.S. Food and Drug Administration; IM, intramuscularly Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998;338:1241­7. Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999;59:1­6. c Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contraception 2001;64:81­5. d el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995;332:983­7. e von Hertzen H, Honkanen H, Piaggio G, Bartfai G, Erdenetungalag R, Gemzell-Danielsson K, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy. WHO Research Group on Post-Ovulatory Methods for Fertility Regulation. BJOG 2003;110:808­18. f Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. MOD Study Trial Group. Obstet Gynecol 2004;103:851­9. g Creinin MD, Vittinghoff E, Schaff E, Klaisle C, Darney PD, Dean C. Medical abortion with oral methotrexate and vaginal misoprostol. Obstet Gynecol 1997;90:611­6. h Creinin MD, Carbonell JL, Schwartz JL, Varela L, Tanda R. A randomized trial of the effect of moistening misoprostol before vaginal administration when used with methotrexate for abortion. Contraception 1999;59:11­6. i Wiebe E, Dunn S, Guilbert E, Jacot F, Lugtig L. Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol. Obstet Gynecol 2002;99:813­9. j Jain JK, Dutton C, Harwood B, Meckstroth KR, Mishell DR Jr. A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Hum Reprod 2002;17:1477­82.

b a

women with pregnancies up to 49 days of gestation, this regimen results in a complete abortion rate of 92­96%. Between 50 days and 56 days of gestation, however, efficacy decreases to 82% (28). Although overall efficacy is equal to the standard regimen of mifepristone­misoprostol, approximately 15­25% of women using methotrexate regimens may wait up to 4 weeks for complete abortion to occur (25, 29, 30). Methotrexate is most commonly administered intramuscularly at a dose based on body surface area (50 mg/m2), the same dose used for the management of ectopic pregnancy (31). However, regimens using 50 mg of methotrexate orally appear to be as effective as those using methotrexate, 50 mg/m2 intramuscularly (29, 32, 33). Misoprostol (800 µg) is administered by the woman 3­7 days later at home. A follow-up examination is per-

formed approximately 1 week after methotrexate administration; a vaginal ultrasound examination is performed to confirm passage of the gestational sac. If abortion has not occurred, the misoprostol dose is repeated. Further follow-up for women requiring a second dose of misoprostol is performed in 4 weeks unless embryonic cardiac activity is still visible on ultrasound examination, in which case patients return in 1 week. If gestational cardiac activity is present 2 weeks after initiating treatment or expulsion has not occurred by the 4-week follow-up visit, aspiration is performed.

Misoprostol Alone

Misoprostol, 800 µg vaginally, when moistened with water, can result in complete abortion rates of 90% in women with pregnancies up to 56 days of gestation

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(10, 34­38). Studies with nonmoistened vaginal misoprostol demonstrated lower rates of 50­67% (39­41). Studies showing that misoprostol alone is effective for abortion often involve complex dosing regimens or require clinician application of the tablets. Additionally, this treatment results in significantly higher rates of side effects (nausea, vomiting, diarrhea, and fever and chills) than those using misoprostol after pretreatment with either mifepristone or methotrexate (10, 34­37). Recent trials with sublingual misoprostol in repeated doses do not appear to improve outcome over vaginal misoprostol and may cause even more side effects (38, 42). A recent randomized, double-blind trial in women with pregnancies up to 56 days of gestation compared a misoprostol-only regimen (800 µg vaginally) with a regimen of 200 mg of mifepristone orally followed 48 hours later by 800 µg of misoprostol vaginally (43). In both groups, misoprostol was repeated every 24 hours for up to three doses. Complete abortion rates for each regimen were 88.0% and 95.7%, respectively (P <.05). The women who received mifepristone aborted much more quickly and required fewer doses of misoprostol compared with women who received misoprostol alone. Mifepristone­misoprostol regimens using 200 mg of mifepristone orally and 800 µg of misoprostol vaginally generally are preferred to regimens using methotrexate and misoprostol or misoprostol only for medical abortion.

Table 2. Features of Medical and Surgical Abortion

Medical Abortion · Usually avoids anesthesia · Requires two or more visits · Days to weeks to complete Surgical Abortion · Allows use of sedation if desired · Usually requires one visit · Complete in a predictable period of time · High success rate (99%) · Bleeding commonly perceived as light · Does not require follow-up in all cases

· Usually avoids invasive procedure · Involves invasive procedure

· Available during early pregnancy · Available during early pregnancy · High success rate (~95%) · Bleeding moderate to heavy for short time · Requires follow-up to ensure completion of abortion

· Patient participation throughout · Patient participation in a singlestep process a multiple-step process

Adapted from Breitbart V. Counseling for medical abortion. Am J Obstet Gynecol 2000;183:S26­33.

Counseling and Symptom Management

Some degree of bleeding and uterine cramping are necessary for the medical abortion process to occur. Other potential side effects of medical abortion include nausea, vomiting, diarrhea, warmth or chills, headache, dizziness, and fatigue (Table 3). Counseling should emphasize that bleeding may be much heavier than menses, potentially with severe cramping. The woman should understand how much bleeding is considered too much. An easy reference for the patient to use is soaking of two pads per hour for 2 hours in a row (46). This is not necessarily a point at which intervention is needed but a time when the woman should call the health care provider. Whether or not it is imperative for the patient to seek emergency care depends on how she is feeling, her baseline hemoglobin, whether the bleeding seems to be slowing, and how far she is from an emergency treatment facility. Pain management is especially important for the woman aborting at home. She should be sent home with appropriate instructions for analgesia with over-thecounter medications, as well as with prescriptions for oral narcotics to use if needed. The incidence of each symptom will depend on the regimen used, the dose and route of administration of the prostaglandin analogue, and gestational age. Gastrointestinal side effects are less common when dry misoprostol is administered vaginally compared with regimens that use oral misoprostol or moistened vaginal misoprostol. Oral ulcers with methotrexate use, although rare, have been reported in the literature.

Counseling Patients

Medical Versus Surgical Abortion

Patient counseling must first include discussion of pregnancy options to be sure that a woman is certain about her decision to have an abortion. If she is uncertain, the decision about abortion technique must be delayed until she has reached a firm decision, even if the delay means that she will be unable to choose a medical option. It is important to respect the patient's autonomy and to separate the decision to terminate the pregnancy from the decision about the method to be used. After a woman has considered her options and has decided to have an abortion, the method must be selected. Most women seeking early abortion will be eligible for both medical and surgical methods. Medical abortion should be considered a medically acceptable alternative to surgical abortion in selected, carefully counseled, and informed women. The general advantages and disadvantages of each approach (Table 2) should be explained early in the counseling process because most women will have a clear preference (44, 45). Even among women who think they are unsure, most will have some preference after counseling (44).

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Table 3. Incidence of Side Effects in Selected North American Trials of Medical Abortion Regimens*

Incidence of Side Effects (%) Nausea Trial Schaff et al (1997) Schaff et al (1999) Creinin (2004)

¶ §

Vomiting Mife 14 13 13 5 14 Miso 14 26 15 23 30

Diarrhea Mife 8 11 5 1 7 Miso 22 23 16 27 25

Headache Mife 18 14 19 10 20 Miso 19 13 29 37 37

Dizziness Mife 22 15 NR 12 20 Miso 37 28 NR 35 37

Thermoregulatory Mife 20 14 NR 9 19 Miso 37 32 23 56 53

Mife 36 45 45 20 39

Miso 36 43 39 44 52

Wiebe et al (2002)|| Creinin (2004)#

Abbreviations: Mife, mifepristone; Miso, misoprostol; NR, not reported *Studies are included only if the incidences of side effects were differentiated between the medications. Fever, warmth, hot flashes, or chills Mifepristone, 600 mg, followed by misoprostol, 800 µg vaginally, 36­48 hours later. (Schaff EA, Stadalius LS, Eisinger SH, Franks P. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract 1997;44:353­60.) § Mifepristone, 200 mg, followed by misoprostol, 800 µg vaginally, 48 hours later. (Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999;59:1­6.) || Mifepristone, 600 mg, followed by misoprostol, 400 µg orally, 36­48 hours later. (Wiebe E, Dunn S, Guilbert E, Jacot F, Lugtig L. Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol. Obstet Gynecol 2002;99:813­9.)

Mifepristone, 200 mg, followed by misoprostol, 800 µg vaginally, 6­8 hours later (first row). (Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol 2004;103:851­9.) # Mifepristone, 200 mg, followed by misoprostol, 800 µg vaginally, 23­25 hours later (second row). (Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol 2004;103: 851­9.)

Need for Follow-up Dilation and Curettage

A failed medical abortion is defined as the presence of gestational cardiac activity on vaginal ultrasonography 2 weeks after the initiation of treatment. No studies have assessed the efficacy of additional doses of mifepristone, methotrexate, or misoprostol after a medical abortion failure. Continuing pregnancies, which should be terminated by surgical evacuation, are typically reported in less than 1% of women who begin treatment at 49 days of gestation or less regardless of regimen. Intervention guidelines vary for women who have a persistent gestational sac seen on ultrasonography without evidence of embryonic cardiac activity or continuing development. Typically, protocols used in mifepristone studies define a retained sac 2 weeks after the administration of mifepristone as an indication for suction evacuation. However, medical abortion studies using methotrexate and misoprostol demonstrate that intervention for a nonviable pregnancy is unnecessary and that expulsion will occur, on average, between 22 and 29 days after the methotrexate is administered (28, 29, 40, 47, 48). With this understanding, the mifepristone studies performed in the United States over the past 6 years have allowed approximately 36 days to elapse after mifepristone administration before recommending surgical intervention (18, 19, 22­25, 27). Most commonly, a woman

who has not aborted and is awaiting delayed expulsion will no longer feel pregnant or have medication-induced symptoms; the patient will be waiting for the onset of bleeding or cramping similar to anticipating the start of menses (28). Providers must differentiate this scenario from women who have incomplete expulsion of the pregnancy tissue, for whom symptoms can include prolonged and irregular bleeding episodes. Early trials of methotrexate and misoprostol showed that serial -hCG evaluations did not aid in the diagnosis of incomplete abortion. All women with an incomplete abortion presented clinically, and the incomplete abortion was not diagnosed by increasing or plateaued -hCG levels (40, 49, 50). Understanding the difference between incomplete abortion and the normal course of medical abortion is important. The sole purpose of ultrasound examination after misoprostol administration is to determine whether the gestational sac is present. After expulsion, the uterus will normally contain ultrasonographically hyperechoic tissue consisting of blood, blood clots, and decidua. Rarely does this finding during medical abortion indicate a need for intervention. In the absence of excessive bleeding, providers can follow such patients conservatively (51). Overall, large studies demonstrate that less than 1% of women undergoing medical abortion will need emergent curettage because of excessive bleeding

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(13, 22, 52­54). Moreover, the risk of clinically significant bleeding and transfusion may be lower in women with pregnancies up to 49 days of gestation compared with those beyond 49 days (11); this relative risk will vary depending on the regimen used. Still, just as for women undergoing surgical abortion, surgical curettage must be available on a 24-hour basis for cases of hemorrhage. Clinicians who wish to provide medical abortion services either should be trained in surgical abortion or should work in conjunction with a clinician who is trained in surgical abortion.

Clinical Considerations and Recommendations

What factors determine whether a woman is a candidate for medical abortion?

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Although medical contraindications are infrequent, social or psychologic contraindications to medical abortion are more common. Women are not good candidates for medical abortion if they do not wish to take responsibility for their care, are anxious to have the abortion over quickly, cannot return for follow-up visits, or cannot understand the instructions because of language or comprehension barriers. Other nonmedical criteria to be considered are access to a phone in case of an emergency and access to 24-hour emergency medical treatment (eg, surgical curettage for hemorrhage). Counseling should include a description of cramping and bleeding and should indicate that, rarely, the process may not be completed for several weeks.

Which pretreatment laboratory tests are needed?

Gestational Age The upper limit of gestational age at which a medical abortion regimen is still an option varies depending on the types, dosages, and routes of administration of the medications. Outpatient treatment with mifepristone­ misoprostol regimens up to 63 days of gestation and for methotrexate­misoprostol regimens up to 49 days of gestation are highly effective. Complete abortion rates among all regimens are highest for earlier gestations and are clinically similar in women with pregnancies up to 49 days of gestation. Between 50 and 63 days of gestation, the use of vaginal misoprostol in regimens with mifepristone results in complete abortion in 96­99% of women (18, 22­24, 26, 27, 43, 53, 55), whereas regimens using oral misoprostol demonstrate significantly lower success rates for these gestational ages. Contraindications Medical contraindications to abortion with mifepristone regimens include confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass, intrauterine device in place, current long-term systemic corticosteroid therapy, chronic adrenal failure, severe anemia, known coagulopathy or anticoagulant therapy, and mifepristone intolerance or allergy. Most clinical trials also exclude women with severe liver, renal, or respiratory disease, uncontrolled hypertension, cardiovascular disease (angina, valvular disease, arrhythmia, or cardiac failure), or severe anemia. Misoprostol should not be used in women with an uncontrolled seizure disorder or those who have an allergy or intolerance to misoprostol or other prostaglandins. Asthma is not a contraindication because misoprostol is a weak bronchodilator.

No special pretreatment laboratory tests are necessary for medical abortion beyond those for surgical abortion. Confirmation of pregnancy by ultrasonography or pregnancy testing is necessary before attempting abortion regardless of method. Pretreatment assessment of hemoglobin or hematocrit and blood typing are imperative, and anti-D immune globulin should be administered if indicated.

What is the risk of infection with medical abortion?

Endometritis is a rare complication of medical abortion. In trials involving more than 500 participants, infection rates typically vary from 0.09% to 0.6% (11, 17, 18, 22, 23, 27, 56, 57). No data exist to support the universal use of prophylactic antibiotics for medical abortion. Five cases of death have been reported in women using mifepristone, 200 mg, followed by misoprostol, 800 µg vaginally, in North America since 2001; all appear to be infectious, with Clostridium sordellii identified in three of the cases (58). The cause of these infections and the relationship of the deaths to mifepristone and misoprostol are still under investigation. Even if related, the death rate would be less than 1 per 100,000 mifepristone procedures, a rate comparable to that for early surgical abortion and miscarriage (59).

Is ultrasonography useful in the medical management of abortion before treatment?

Gestational age should be confirmed by clinical evaluation or ultrasonography. Only 85% of U.S. women are able to predict gestational age within 2 weeks of the gestational age assigned by the clinician using ultrasound examination (60). Additionally, medical abortion studies in U.S. women have found that the gestational age determined by LMP was confirmed for only 40­60% of study

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participants (14, 27, 61). Because efficacy for some regimens decreases significantly with increasing gestational age, the clinical relevance of erroneous gestational age assignment will vary according to the regimen used. Although not required, all major U.S. trials of mifepristone or methotrexate have relied on transvaginal ultrasonography for dating and follow-up. In France, however, clinicians use ultrasonography for preabortion screening only when they find a discrepancy between uterine size and dating by LMP and when patients present with bleeding or symptoms suggestive of ectopic pregnancy. Pregnancy termination services in France are offered only by authorized abortion clinics staffed by highly experienced providers. The high efficacy and safety results in the French trials suggest that this selective use of ultrasonography suffices when medical abortion is provided by experienced clinicians. A concern when providing early abortion services is the possibility of an undiagnosed extrauterine gestation. Although the ectopic pregnancy rate in the general population is currently around 19­21 per 1,000 pregnancies (62, 63), ectopic pregnancy rates in studies of women seeking abortion are consistently lower. A study of surgical abortion in women with pregnancies less than 42 days of gestation in the United States found the ectopic pregnancy rate to be 5.9 per 1,000 pregnancies (64). Similarly, the largest published study of medical abortion involved 16,369 women with pregnancies up to 49 days of gestation, 21 of whom were excluded from the analysis because of an ectopic pregnancy, yielding an ectopic pregnancy rate of 1.3 per 1,000 pregnancies (57). Although ectopic pregnancy in a population of women seeking early abortion is rare, women with significant medical risk factors or history (eg, unilateral pain and vaginal bleeding) should have pretreatment ultrasonography.

What methods can be used to confirm complete abortion?

Transvaginal ultrasonography offers an efficient means of assessing outcome in patients who undergo medical abortion. Its primary objective is to determine if the gestational sac is absent (with or without the presence of other ultrasonographically hyperechoic tissue). However, French clinicians, who have extensive experience with medical abortion, use ultrasonography significantly less than American clinicians (65). One explanation for this difference may be less familiarity with the process by both American clinicians and patients; another reason could be liability concerns in the United States. A study of U.S. providers indicated that ultrasonography is perceived to be unnecessary to assess abortion outcome for most women (66). Researchers asked physicians if they felt

comfortable with their assessment without ultrasonography or if they would feel better in that situation with an ultrasound examination to confirm their impression based on the patient's history and physical examination. Physicians thought an ultrasound examination was not needed in 60% of the women who were ultimately found to have expelled the gestational sac. However, the gestational sac was still present in 29% of women for whom physicians believed ultrasonography was not indicated. Methods to verify abortion include reports of bleeding combined with evidence of uterine involution on pelvic examination or hCG testing. When misoprostol is administered 2­5 days after methotrexate or mifepristone, -hCG concentrations should decrease by at least 50% within 1 week of initiating the medication regimen. However, performing sensitive serum or urine hCG assays (detection threshold, 25­50 mIU/mL) too soon after the termination of a pregnancy may result in an erroneous diagnosis of failed medical abortion. Two trials using methotrexate and misoprostol found that the average time to disappearance of -hCG is 33­34 days and may take as long as 90 days (40, 67). The utility of nonsensitive urine hCG assays in follow-up after mifepristone and misoprostol administration warrants investigation. In clinical trials with methotrexate and misoprostol, only about half of the women who thought they had aborted actually had done so (28). Moreover, women may experience symptom resolution consistent with a complete medical abortion and still have a persistent gestational sac (28), or even an ectopic pregnancy (22). The importance of patient follow-up must be emphasized because failure rates for medical abortion are higher than those for surgical techniques. However, recent data suggest that for most women having an abortion with mifepristone and misoprostol, no follow-up may be needed other than a telephone conversation. One report compared clinicians' and patients' impressions of whether or not expulsion occurred based solely on the patient's history with the results of vaginal ultrasonography performed approximately 1 week after initiating treatment (68). When the clinician and the patient both thought that expulsion had occurred, they were correct 99% of the time. Additional studies are needed to validate the premise that such women need only a home pregnancy test for follow-up and that office evaluation should be required only if either the clinician or the patient is not certain that expulsion has occurred.

Do nonsteroidal antiinflammatory drugs affect the success rates for medical abortion?

Cramping pain for patients who are not undergoing abortion usually is treated with ibuprofen or other non-

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steroidal antiinflammatory drugs (NSAIDs). Although NSAIDs inhibit the synthesis of new prostaglandins, they do not block the action of prostaglandin receptors; therefore, such agents should not inhibit the action of a prostaglandin used for medical abortion. The only report to evaluate the effects of analgesics on abortion outcome was a retrospective analysis of NSAIDs and complete abortion in 416 women who received misoprostol following methotrexate for medical abortion of pregnancies up to 56 days of gestation (69). The use of ibuprofen did not seem to interfere with the action of misoprostol to induce uterine contractions and pregnancy expulsion. Therefore, NSAIDs such as ibuprofen are not contraindicated for women undergoing a medical abortion.

Summary of Recommendations and Conclusions

The following recommendations are based primarily on good and consistent scientific evidence (Level A):

Medical abortion should be considered a medically acceptable alternative to surgical abortion in selected, carefully counseled, and informed women. The FDA-approved protocol of 600 mg of mifepristone orally followed approximately 48 hours later by 400 µg of misoprostol orally is safe and effective for medical abortion through 49 days of gestation (calculated from the first day of the LMP). Compared with the FDA-approved regimen, mifepristone­misoprostol regimens using 200 mg of mifepristone orally and 800 µg of misoprostol vaginally are associated with a decreased rate of continuing pregnancies, decreased time to expulsion, fewer side effects, improved complete abortion rates, and lower cost for women with pregnancies up to 63 days of gestation based on LMP. A methotrexate­misoprostol regimen is appropriate for medical abortion only in pregnancies up to 49 days of gestation. Women using this regimen may wait up to 4 weeks for complete abortion to occur. Mifepristone­misoprostol regimens using 200 mg of mifepristone orally and 800 µg of misoprostol vaginally are generally preferred to regimens using methotrexate and misoprostol or misoprostol only for medical abortion. A patient can administer misoprostol safely and effectively, orally or vaginally, in her home as part of a medical abortion regimen.

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How should a patient be counseled about potential teratogenicity if a medical method fails to lead to abortion?

Because teratogenicity of medical abortifacients becomes an important issue if the pregnancy continues, patients must be informed of the need for a surgical abortion in the event of a continuing pregnancy. There is no evidence to date of a teratogenic effect of mifepristone. However, methotrexate is an antimetabolite that can cause fetal anomalies (70, 71). Evidence suggests that misoprostol also can result in congenital anomalies when used during the first trimester, possibly due to mild uterine contractions resulting in decreased blood flow during organogenesis (72). Anomalies associated with misoprostol use that have been described in the literature include defects in the frontal or temporal bones (73) and limb abnormalities with or without Möbius sequence (masklike facies with bilateral sixth and seventh nerve palsy and frequently coincident micrognathia) (74­77). No conclusions regarding teratogenicity can be drawn from these reports because of the extremely small sample sizes.

The following recommendations are based primarily on limited scientific evidence (Level B):

Because teratogenicity of medical abortifacients becomes an important issue if the pregnancy continues, patients must be informed of the need for a surgical abortion in the event of a failed abortion. Gestational age should be confirmed by clinical evaluation or ultrasonography.

Does medical abortion affect future fertility?

Future fertility following medical abortion has been evaluated only within a 1-year period after medical abortion in a group of 93 women who received methotrexate and misoprostol for abortion (78). Although none of the women were actively attempting to achieve pregnancy, 25% became pregnant, a rate higher than would be expected for a group of women using contraception. By comparison, another report indicated a pregnancy rate of 13% within 1 year after a first surgical abortion (79).

The following recommendations are based primarily on consensus and expert opinion (Level C):

Surgical curettage must be available on a 24-hour basis for cases of hemorrhage, even though less than

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1% of women having a medical abortion will need a curettage because of excessive bleeding. Pretreatment anti-D immune globulin should be administered if indicated. No data exist to support the universal use of prophylactic antibiotics for medical abortion.

13. Aubény E, Peyron R, Turpin CL, Renault M, Targosz V, Silvestre L, et al. Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol [published erratum appears in Int J Fertil Menopausal Stud 1996;41:56]. Int J Fertil Menopausal Stud 1995;40 (suppl 2):85­91. (Level II-3) 14. Creinin MD, Spitz IM. Use of various ultrasound criteria to evaluate the efficacy of mifepristone and misoprostol for medical abortion. Am J Obstet Gynecol 1999; 181:1419­24. (Level II-3) 15. McKinley C, Thong KJ, Baird DT. The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol. Hum Reprod 1993;8:1502­5. (Level I) 16. el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995;332:983­7. (Level I) 17. Honkanen H, Piaggio G, Hertzen H, Bartfai G, Erdenetungalag R, Gemzell-Danielsson K, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. WHO Research Group on Post-Ovulatory Methods for Fertility Regulation. BJOG 2004;111:715­25. (Level I) 18. Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception 2000;61:41­6. (Level II-3) 19. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy [published erratum appears in Contraception 2002;66:481]. Contraception 2002;66:247­50. (Level I) 20. von Hertzen H, Honkanen H, Piaggio G, Bartfai G, Erdenetungalag R, Gemzell-Danielsson K, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy. WHO Research Group on Post-Ovulatory Methods for Fertility Regulation. BJOG 2003;110:808­18. (Level I) 21. Schaff EA, Stadalius LS, Eisinger SH, Franks P. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract 1997;44:353­60. (Level II-3) 22. Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999;59:1­6. (Level II-3) 23. Schaff EA, Fielding SL, Westhoff C, Ellertson C, Eisinger SH, Stadalius LS, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial [published erratum appears in JAMA 2000;284:2597]. JAMA 2000;284:1948­53. (Level I) 24. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contraception 2001;64: 81­5. (Level I)

References

1. Finer LB, Henshaw SK. Abortion incidence and services in the United States in 2000. Perspect Sex Reprod Health 2003;35:6­15. (Level II-3) 2. Gravanis A, Schaison G, George M, de Brux J, Satyaswaroop PG, Baulieu EE, et al. Endometrial and pituitary responses to the steroidal antiprogestin RU 486 in postmenopausal women. J Clin Endocrinol Metab 1985;60:156­63. (Level II-3) 3. Johannisson E, Oberholzer M, Swahn ML, Bygdeman M. Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486. Contraception 1989:39;103­17. (Level II-2) 4. Swahn ML, Bygdeman M. The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin. Br J Obstet Gynaecol 1988:95;126­34. (Level II-2) 5. Danielsson KG, Marions L, Rodriguez A, Spur BW, Wong PY, Bygdeman M. Comparison between oral and vaginal administration of misoprostol on uterine contractility. Obstet Gynecol 1999;93:275­80. (Level II-2) 6. Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997;90:88­92. (Level II-1) 7. Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception 2005;71:22­5. (Level II-3) 8. Tang OS, Schweer H, Seyberth HW, Lee SW, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod 2002;17:332­6. (Level I) 9. Wiebe ER. Tamoxifen compared to methotrexate when used with misoprostol for abortion. Contraception 1999;59:265­70. (Level I) 10. Jain JK, Meckstroth KR, Park M, Mishell DR Jr. A comparison of tamoxifen and misoprostol to misoprostol alone for early pregnancy termination. Contraception 2000;60:353­6. (Level I) 11. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998;338:1241­7. (Level II-3) 12. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial. World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation. BJOG 2000; 107:524­30. (Level I)

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25. Wiebe E, Dunn S, Guilbert E, Jacot F, Lugtig L. Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol. Obstet Gynecol 2002;99:813­9. (Level I) 26. Creinin MD, Potter C, Holovanisin M, Janczukiewicz L, Pymar HC, Schwartz JL, et al. Mifepristone and misoprostol and methotrexate/misoprostol in clinical practice for abortion. Am J Obstet Gynecol 2003;188:664­9. (Level II-3) 27. Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. MOD Study Trial Group. Obstet Gynecol 2004;103:851­9. (Level I) 28. Creinin MD, Vittinghoff E, Keder L, Darney PD, Tiller G. Methotrexate and misoprostol for early abortion: a multicenter trial. I. Safety and efficacy. Contraception 1996;53:321­7. (Level II-3) 29. Creinin MD, Vittinghoff E, Schaff E, Klaisle C, Darney PD, Dean C. Medical abortion with oral methotrexate and vaginal misoprostol. Obstet Gynecol 1997;90:611­6. (Level II-3) 30. Creinin MD, Carbonell JL, Schwartz JL, Varela L, Tanda R. A randomized trial of the effect of moistening misoprostol before vaginal administration when used with methotrexate for abortion. Contraception 1999;59:11­6. (Level I) 31. Lipscomb GH, Bran D, McCord ML, Portera JC, Ling FW. Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998;178:1354­8. (Level II-3) 32. Carbonell JL, Varela L, Velazco A, Cabezas E, Fernandez C, Sanchez C. Oral methotrexate and vaginal misoprostol for early abortion. Contraception 1998;57:83­8. (Level I) 33. Creinin MD. Oral methotrexate and vaginal misoprostol for early abortion. Contraception 1996;54:15­8. (Level I) 34. Carbonell JL, Varela L, Velazco A, Fernandez C. The use of misoprostol for termination of early pregnancy. Contraception 1997;55:165­8. (Level II-3) 35. Carbonell JL, Varela L, Velazco A, Fernandez C, Sanchez C. The use of misoprostol for abortion at 9 weeks' gestation. Eur J Contracept Reprod Health Care 1997;2: 181­5. (Level II-3) 36. Esteve JL, Varela L, Velazco A, Tanda R, Cabezas E, Sanchez C. Early abortion with 800 micrograms of misoprostol by the vaginal route. Contraception 1999; 59:219­25. (Level II-3) 37. Jain JK, Meckstroth KR, Mishell DR Jr. Early pregnancy termination with intravaginally administered sodium chloride solution-moistened misoprostol tablets: historical comparison with mifepristone and oral misoprostol. Am J Obstet Gynecol 1999;181:1386­91. (Level II-2) 38. Singh K, Fong YF, Dong F. A viable alternative to surgical vacuum aspiration: repeated doses of intravaginal misoprostol over 9 hours for medical termination of pregnancies up to eight weeks. BJOG 2003;110:175­80. (Level II-3)

39. Bugalho A, Faundes A, Jamisse L, Usfa M, Maria E, Bique C. Evaluation of the effectiveness of vaginal misoprostol to induce first trimester abortion. Contraception 1996;53:244­6. (Level II-1) 40. Creinin MD, Vittinghoff E. Methotrexate and misoprostol vs misoprostol alone for early abortion. A randomized controlled trial. JAMA 1994;272:1190­5. (Level I) 41. Koopersmith TB, Mishell DR Jr. The use of misoprostol for termination of early pregnancy. Contraception 1996;53:238­42. (Level I) 42. Tang OS, Miao BY, Lee SW, Ho PC. Pilot study on the use of repeated doses of sublingual misoprostol in termination of pregnancy up to 12 weeks gestation: efficacy and acceptability. Hum Reprod 2002;17:654­8. (Level II-3) 43. Jain JK, Dutton C, Harwood B, Meckstroth KR, Mishell DR Jr. A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Hum Reprod 2002;17: 1477­82. (Level I) 44. Creinin MD. Randomized comparison of efficacy, acceptability and cost of medical versus surgical abortion. Contraception 2000;62:117­24. (Level I) 45. Henshaw RC, Naji SA, Russell IT, Templeton AA. Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment. BMJ 1993;307:714­7. (Level II-1) 46. Creinin MD, Aubény E. Medical abortion in early pregnancy. In: Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG, editors. A clinician's guide to medical and surgical abortion. New York (NY): Churchill Livingstone; 1999. p. 91­106. (Level III) 47. Creinin MD, Vittinghoff E, Galbraith S, Klaisle C. A randomized trial comparing misoprostol three and seven days after methotrexate for early abortion. Am J Obstet Gynecol 1995;173:1578­84. (Level I) 48. Creinin MD. Medical abortion with methotrexate 75 mg intramuscularly and vaginal misoprostol. Contraception 1997;56:367­71. (Level II-3) 49. Creinin MD, Darney PD. Methotrexate and misoprostol for early abortion [published erratum appears in Contraception 1994;49:99]. Contraception 1993;48:339­48. (Level II-3) 50. Creinin MD. Methotrexate for abortion at 42 days gestation. Contraception 1993;48:519­25. (Level II-3) 51. Harwood B, Meckstroth KR, Mishell DR, Jain JK. Serum beta-human chorionic gonadotropin levels and endometrial thickness after medical abortion. Contraception 2001;63:255­6. (Level III) 52. Allen RH, Westhoff C, De Nonno L, Fielding SL, Schaff EA. Curettage after mifepristone-induced abortion: frequency, timing, and indications. Obstet Gynecol 2001; 98:101­6. (Level II-3) 53. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regimen for early medical abortion: a report of 2000 consecutive cases. Hum Reprod 1998;13:2962­5. (Level II-3)

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54. Winikoff B, Sivin I, Coyaji KJ, Cabezas E, Xiao B, Gu S, et al. Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: a comparative trial of mifepristone-misoprostol versus surgical abortion. Am J Obstet Gynecol 1997;176:431­7. (Level II-3) 55. Bartley J, Brown A, Elton R, Baird DT. Double-blind randomized trial of mifepristone in combination with vaginal gemeprost or misoprostol for induction of abortion up to 63 days gestation. Hum Reprod 2001;16:2098­102. (Level I) 56. Silvestre L, Dubois C, Renault M, Rezvani Y, Baulieu EE, Ulmann A. Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience. N Engl J Med 1990;322: 645­8. (Level II-3) 57. Ulmann A, Silvestre L, Chemama L, Rezvani Y, Renault M, Aguillaume CJ, et al. Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women. Acta Obstet Gynecol Scand 1992;71:278­83. (Level II-3) 58. Centers for Disease Control and Prevention. Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001­2005. MMWR Morb Mortal Wkly Rep 2005;54:724. 59. Grimes DA. Risk of mifepristone abortion in context. Contraception 2005;71:161. 60. Ellertson C, Elul B, Ambardekar S, Wood L, Carroll J, Coyaji K. Accuracy of assessment of pregnancy duration by women seeking early abortions. Lancet 2000;355: 877­81. (Level III) 61. Creinin MD, Jerald H. Success rates and estimation of gestational age for medical abortion vary with transvaginal ultrasonographic criteria. Am J Obstet Gynecol 1999; 180:35­41. (Level II-3) 62. Ectopic pregnancy--United States, 1988-1989. MMWR Morb Mortal Wkly Rep 1992;41:591­4. (Level II-3) 63. Van Den Eeden SK, Shan J, Bruce C, Glasser M. Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 2005;105: 1052­7. (Level II-3) 64. Edwards J, Creinin MD. Surgical abortion for gestations of less than 6 weeks. Curr Probl Obstet Gynecol Fertil 1997;20:11­9. (Level II-3) 65. Paul M, Schaff E, Nichols M. The roles of clinical assessment, human chorionic gonadotropin assays, and ultrasonography in medical abortion practice. Am J Obstet Gynecol 2000;183(suppl 2):S34­43. (Level III) 66. Fielding SL, Schaff EA, Nam NY. Clinicians' perception of sonogram indication for mifepristone abortion up to 63 days. Contraception 2002;66:27­31. (Level III)

67. Schaff EA, Eisinger SH, Franks P, Kim SS. Combined methotrexate and misoprostol for early induced abortion. Arch Fam Med 1995;4:774­9. (Level II-3) 68. Rossi B, Creinin MD, Meyn LA. Ability of the clinician and patient to predict the outcome of mifepristone and misoprostol medical abortion. Contraception 2004;70: 313­7. (Level II-3) 69. Creinin MD, Shulman T. Effect of non-steroidal antiinflammatory drugs on the action of misoprostol in a regimen for early abortion. Contraception 1997;56:165­8. (Level II-2) 70. Darab DJ, Minkoff R, Sciote J, Sulik KK. Pathogenesis of median facial clefts in mice treated with methotrexate. Teratology 1987;36:77­86. (Level III) 71. Kozlowski RD, Steinbrunner JV, MacKenzie AH, Clough JD, Wilke WS, Segal AM. Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med 1990;88:589­92. (Level III) 72. Yip SK, Tse AO, Haines CJ, Chung TK. Misoprostol's effect on uterine arterial blood flow and fetal heart rate in early pregnancy. Obstet Gynecol 2000;95:232­5. (Level II-3) 73. Fonseca W, Alencar AJ, Mota FS, Coelho HL. Misoprostol and congenital malformations. Lancet 1991;338: 56. (Level III) 74. Gonzalez CH, Vargas FR, Perez AB, Kim CA, Brunoni D, Marques-Dias MJ, et al. Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet 1993;47:59­64. (Level III) 75. Marques-Dias MJ, Gonzalez CH, Rosemberg S. Mobius sequence in children exposed in utero to misoprostol: neuropathological study of three cases. Birth Defects Res A Clin Mol Teratol 2003;67:1002­7. (Level III) 76. Pastuszak AL, Schuler L, Speck-Martins CE, Coelho KE, Cordello SM, Vargas F, et al. Use of misoprostol during pregnancy and Mobius' syndrome in infants. N Engl J Med 1998;338:1881­5. (Level II-2) 77. Wiebe ER. Abortion induced with methotrexate and misoprostol: a comparison of various protocols. Contraception 1997;55:159­63. (Level II-1) 78. Creinin MD. Conception rates after abortion with methotrexate and misoprostol. Int J Gynaecol Obstet 1999;65:183­8. (Level II-2) 79. Steinhoff PG, Smith RG, Palmore JA, Diamond M, Chung CS. Women who obtain repeat abortions: a study based on record linkage. Fam Plann Perspect 1979;11:30­8. (Level III)

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The MEDLINE database, the Cochrane Library, and ACOG's own internal resources and documents were used to conduct a literature search to locate relevant articles published between January 1985 and June 2005. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetrician­gynecologists were used. Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force: Evidence obtained from at least one properly designed randomized controlled trial. II-1 Evidence obtained from well-designed controlled trials without randomization. II-2 Evidence obtained from well-designed cohort or case­control analytic studies, preferably from more than one center or research group. II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence. III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees. Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories: Level A--Recommendations are based on good and consistent scientific evidence. Level B--Recommendations are based on limited or inconsistent scientific evidence. Level C--Recommendations are based primarily on consensus and expert opinion. I

Copyright © October 2005 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to make photocopies should be directed to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400. The American College of Obstetricians and Gynecologists 409 12th Street, SW PO Box 96920 Washington, DC 20090-6920

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Safe Abortion:

Technical and Policy Guidance for Health Systems

Safe Abortion:

Technical and Policy Guidance for Health Systems

Acknowledgments

The World Health Organization gratefully acknowledges the contribution of those who have collaborated on the elaboration of the publication, and in particular the participants at the WHO Technical Consultation on Safe Abortion held in Geneva in September 2000, for their contributions and subsequent review. The preparation and printing of the publication, and holding of the Technical Consultation, were made possible through financial contributions from the David and Lucille Packard Foundation, the Ford Foundation, the Swedish International Development Cooperation Agency, and the United Kingdom Department for International Development. WHO Library Cataloguing-in-Publication Data World Health Organization. Safe abortion : technical and policy guidance for health systems. 1.Abortion, Induced - methods 2.Abortion, Induced - standards. 3.Prenatal care - organization and administration 4.Prenatal care - standards 5.Maternal welfare 6.Health policy 7. Guidelines I.Title ISBN 92 4 159034 3 (NLM classification: WQ 440)

World Health Organization 20 Avenue Appia 1211 Geneva 27 Switzerland Fax: +41-22-791-4171 Email: [email protected] Website: http://www.who.int/reproductive-health/

© World Health Organization 2003 All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications ­ whether for sale or for noncommercial distribution ­ should be addressed to Publications, at the above address (fax: +41 22 791 4806; email: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. Designed by Clarus Design, UK

Contents

Introduction Chapter 1: Safe abortion services: the public health challenge Summary 1 2 3 4 5 6 Background Induced abortion Unsafe abortion Safe abortion Legal, policy and contextual considerations The challenge ­ making safe services available 10 11 12 12 14 14 16 17 7 2 Methods of abortion 29 29 30 30 31 31 32 32 33 33 34

Summary 2.1 Cervical preparation 2.2 Pain management 2.2.1 2.2.2 Medication for pain Anaesthesia

2.3 Surgical abortion 2.3.1 2.3.2 2.3.3 2.3.4 Vacuum aspiration Dilatation and curettage Dilatation and evacuation Other surgical methods of abortion for use in later pregnancy 2.3.5 Tissue examination following surgical abortion 2.4 Medical methods of abortion 2.4.1 Mifepristone and prostaglandin

References Chapter 2: Clinical care for women undergoing abortion Summary 1 Pre-abortion care 1.1 Patient history 1.2 Physical examination 1.3 Laboratory testing 1.4 Ultrasound scanning 1.5 Pre-existing conditions 1.6 Reproductive tract infections (RTIs) 1.7 Ectopic pregnancy 1.8 Rh-isoimmunisation 1.9 Cervical cytology 1.10 Information and counselling 1.10.1 1.10.2 1.10.3 Decision-making counselling Information on abortion procedures Contraceptive information and services

20 23 23 23 24 24 24 25 25 25 26 26 26 27 27 2.4.2

35

35 36 36

2.4.1.1 Up to 9 completed weeks since last menstrual period 2.4.1.2 From 9 to 12 completed weeks since last menstrual period 2.4.1.3 After 12 completed weeks since last menstrual period Misoprostol or gemeprost alone

38

38

38 38

2.4.2.1 Up to 12 completed weeks since last menstrual period 2.4.2.2 After 12 completed weeks since last menstrual period 2.4.3 Other medical abortion agents

39

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2.5 Other issues related to abortion procedures 2.5.1 Infection prevention and control

40 40

Chapter 3: Putting services in place Summary 1 2 Assessing the current situation Establishing national norms and standards 2.1 Types of abortion services and where they can be provided 54 55 58 59

2.5.1.1 Handwashing and use of protective barriers 40 2.5.1.2 Cleaning 2.5.1.3 Safe disposal of waste contaminated with body fluids 2.5.1.4 Safe handling and disposal of "sharps" 2.5.1.5 Safe cleaning of equipment after use 2.5.2 Managing abortion complications 41 41 42 42 42 42 43 43 43 43 44 44 44 44 45 45 46 40 40

2.1.1 Community level 2.1.2 Primary-care facility level 2.1.3 District hospital (first referral) level 2.1.4 Secondary and tertiary referral hospitals 2.2 Essential equipment, supplies, medications and facility capabilities 2.2.1 Regulatory requirements for drugs and devices 2.3 Referral mechanisms 2.4 Respect for women's informed decision-making, autonomy, confidentiality and privacy, with attention to the special needs of adolescents 2.4.1 Informed and free decision-making 2.4.2 Autonomy in decision-making (third party authorization) 2.4.3 Confidentiality 2.4.4 Privacy 2.5 Special provisions for women who have suffered rape

59 59 60 60 62

2.5.2.1 Incomplete abortion 2.5.2.2 Failed abortion 2.5.2.3 Haemorrhage 2.5.2.4 Infection 2.5.2.5 Uterine perforation 2.5.2.6 Anaesthesia-related complications 2.5.2.7 Long-term sequelae 3 Follow-up 3.1 Recovery period 3.1.1 3.1.2 Surgical methods of abortion Medical methods of abortion

64 64 65

65 66

3.2 Contraceptive method provision and STI counselling 3.3 Instructions for care after abortion References

68 68 68

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3

Ensuring provider skills and performance 3.1 Provider skills and training 3.1.1 Training programmes 3.2 Supervision 3.3 Certification and licensing of health professionals and facilities

69 69 70 72 73

4

Creating an enabling policy environment 4.1 Goals 4.2 Constellation of services 4.3 Methods of abortion 4.4 Range of providers 4.5 Service fees

87 88 88 88 88 89 89 89 90 95

4

Monitoring and evaluation of services 4.1 Monitoring 4.2 Evaluation

73 73 76 76 77 77 78 5

4.6 Health system requirements/quality of care 4.7 Public information Removing administrative and regulatory barriers

5

Financing 5.1 Cost to the facility or health system 5.2 Making services affordable for women

References Annex 1: Annex 2: Further reading and resources International consensus documents in relation to safe abortion Annex 3: Instruments and supplies for manual vacuum aspiration (MVA) Annex 4: Contraception following abortion

96 98

References Chapter 4: Legal and policy considerations Summary 1 2 3 Women's health and international agreements Laws and their implementation Understanding legal grounds for abortion 3.1 When there is a threat to the woman' s life 3.2 When there is a threat to the woman's physical or mental health 3.3 When pregnancy is the result of rape or incest 3.4 When there is fetal impairment 3.5 For economic and social reasons 3.6 On request 3.7 Limits on length of pregnancy 3.8 Other limits

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Safe Abortion: Technical and Policy Guidance for Health Systems

Safe Abortion: Technical and Policy Guidance for Health Systems

Introduction In October 2000, at the United Nations Millennium Summit, all countries agreed on the global imperative to reduce poverty and inequities. The need to improve maternal health was identified as one of the key Millennium Development Goals, with a target of reducing levels of maternal mortality by three-quarters between 1990 and 2015. The causes of maternal deaths are multiple. Women die because complications during labour and delivery go unrecognised or are inadequately managed. They die from diseases such as malaria, that are aggravated by pregnancy. They die because of complications arising early in pregnancy, sometimes even before they are aware of being pregnant, such as ectopic pregnancy. And they die because they seek to end unwanted pregnancies but lack access to appropriate services. Achieving the Millennium Development Goal of improved maternal health and reducing maternal mortality requires actions on all these fronts. Despite dramatically increased use of contraception over the past three decades, an estimated 40-50 million abortions occur annually, nearly half of them in circumstances that are unsafe. Globally, approximately 13% of all maternal deaths are due to complications of unsafe abortion. In addition to some 70,000 women who die each year, tens of thousands suffer long-term health consequences including infertility. Even where family planning is widely accessible, pregnancies occur due to contraceptive failure, difficulties with use, non use or as a result of incest or rape. Pregnancy may pose a threat to the woman's life or to her physical and mental health. In recognition of such circumstances, nearly all countries in the world have passed laws that permit termination of pregnancy under specified conditions. In some settings, abortion is legal only to save the woman's life; in others, abortion is allowed upon request by the woman. Health systems need to respond accordingly. The role of the World Health Organization is to develop norms and standards and provide advice to Member States in order to strengthen the capacity of health systems. For over three decades WHO has assisted governments, international agencies and non-governmental organizations to plan and deliver maternal health services, including managing complications of unsafe abortion and providing high-quality family planning services. At the Special Session of the United Nations General Assembly in June 1999, Governments agreed that "in circumstances where abortion is not against the law, health systems should train and equip health-service providers and should take other measures to ensure that such abortion is safe and accessible. Additional measures should be taken to safeguard women's health." This document provides guidance to turn this agreement into reality.

Introduction Safe Abortion: Technical and Policy Guidance for Health Systems

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Safe abortion services: Chapter 1 the public health challenge

Chapter 1 ­ Making safe abortion services available: the public health challenge

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Safe Abortion: Technical and Policy Guidance for Health Systems

Chapter 1 Summary

An estimated 46 million pregnancies end in induced abortion each year. Nearly 20 million of these are estimated to be unsafe. About 13 per cent of pregnancy-related deaths have been attributed to complications of unsafe abortion, and probably number about 67,000 deaths annually. In developing countries, the risk of death following complications of unsafe abortion procedures is several hundred times higher than that of an abortion performed professionally under safe conditions. Complications resulting from unsafe abortion contribute to serious sequelae for women's health such as infertility. Since no contraceptive is 100 per cent effective, there will continue to be unwanted pregnancies which women may seek to end by induced abortion. In almost all countries the law permits abortion to save the woman's life and in most countries abortion is allowed to preserve the physical and mental health of the woman. Safe abortion services, as provided by law, therefore need to be available, provided by well-trained health personnel supported by policies, regulations and a health systems infrastructure, including equipment and supplies, so that women can have rapid access to these services.

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Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

1

Background

The International Conference on Population and Development (ICPD) in Cairo in 1994 and the Fourth World Conference on Women (FWCW) in Beijing in 1995 both affirmed the human rights of women in the area of reproductive and sexual health. The Cairo Conference agreed that "Reproductive rights embrace certain human rights that are already recognised in national laws, international human rights documents and other consensus documents. These rights rest on the recognition of the basic rights of all couples and individuals to decide freely and responsibly the number, spacing and timing of their children and to have the information and means to do so, and the right to attain the highest standard of sexual and reproductive health." (United Nations 1995, paragraph 7.3). In Beijing, Governments agreed that "The human rights of women include their right to have control over and decide freely and responsibly on matters related to their sexuality, including sexual and reproductive health, free of coercion, discrimination and violence. Equal relationships between women and men in matters of sexual relations and reproduction, including full respect for the integrity of the person, require mutual respect, consent and shared responsibility for sexual behaviour and its consequences." (United Nations 1996, paragraph 96).

On the subject of abortion in particular, at the Cairo Conference, Governments of the world recognised unsafe abortion as a major public health concern, and pledged their commitment to reducing the need for abortion through expanded and improved family planning services, while at the same time recognising that, in circumstances where not against the law, abortion should be safe (United Nations 1995, paragraph 8.25). One year later, the Beijing Conference affirmed these agreements and also called for Governments to consider reviewing laws containing punitive measures against women who have undergone illegal abortions (United Nations 1996, paragraph 106). The United Nations General Assembly review and appraisal of the implementation of ICPD in 1999 (ICPD + 5) further agreed that, "in circumstances where abortion is not against the law, health systems should train and equip health-service providers and should take other measures to ensure that such abortion is safe and accessible. Additional measures should be taken to safeguard women's health." (United Nations 1999, paragraph 63.iii). For many years, the World Health Organization (WHO) and other organisations have elaborated guidelines for the prevention of unsafe abortion and the management of its complications (see Annex 1). This document provides technical guidance to Governments, policy-makers, programme managers and health workers on how to implement paragraph 63.iii cited above.

Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

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Induced abortion

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Unsafe abortion

Of the 210 million pregnancies that occur each year, about 46 million (22 per cent) end in induced abortion and, globally, the vast majority of women are likely to have at least one abortion by the time they are 45 (Alan Guttmacher Institute 1999). Where effective contraceptive methods are available and widely used, the total abortion rate declines sharply (Bongaarts and Westoff 2000), but has nowhere declined to zero for several reasons. First, millions of women and men either do not have access to appropriate contraceptive methods, or do not have adequate information and support to use them effectively. Second, no contraceptive method is 100 per cent effective. Table 1.1 illustrates this point, using estimates calculated for "perfect use" of a method, in which the user always follows instructions for use exactly, and those calculated for "typical use" which takes into account that people do not always manage to use contraceptives perfectly. Third, high rates of violence against women including in the home and in war lead to unwanted pregnancies. Fourth, changing circumstances, such as divorce or other crisis, can result in a wanted pregnancy becoming unwanted.

Even if all contraceptive users were to use methods perfectly all the time, there would still be nearly six million accidental pregnancies annually. Thus, even with high rates of contraceptive use, unwanted pregnancies will occur which women may seek to end by induced abortion. An unsafe abortion is "a procedure for terminating an unwanted pregnancy either by persons lacking the necessary skills or in an environment lacking the minimal medical standards, or both" (World Health Organization 1992). About 20 million, or nearly half, of the induced abortions annually are estimated to be unsafe. Ninety-five per cent of these occur in developing countries (World Health Organization 1998). Globally, there is a ratio of one unsafe abortion for every seven live births (World Health Organization 1998), but in some regions the ratio is much higher. For instance, in Latin America and the Caribbean, there is more than one unsafe abortion for every three live births (World Health Organization 1998).

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Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

Table 1.1 Estimated accidental pregnancies resulting from contraceptive failure worldwide (estimates for 1993) Contraceptive method Estimated failure rate (perfect use)1 % Female sterilization Male sterilization Injectables IUD Pill Male condom Vaginal barrier Periodic abstinence Withdrawal Total 0.50 0.10 0.30 0.60 0.10 3.00 6.00 3.00 4.00 Estimated failure rate (typical use)1 % 0.50 0.15 0.30 0.80 5.00 14.00 20.00 25.00 19.00 Number of users2 Number of accidental pregnancies (perfect use) 000's 1,005 41 78 894 78 1,530 240 780 1,240 5,886 Number of accidental pregnancies (typical use) 000's 1,005 62 78 1,192 3,900 7,140 800 6,500 5,890 26,567

000's 201,000 41,000 26,000 149,000 78,000 51,000 4,000 26,000 31,000 607,000

1 2

Trussel (1998) Estimates based on USA data. Failure rates are expressed as percentage of women who will become pregnant during one year while using the method. United Nations Population Division (2002). Estimated number of women aged 15-49 who are in a marital or consensual union.

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3

Unsafe abortion continued

4

Safe abortion

About 13 per cent of pregnancy-related deaths have been attributed to complications of unsafe abortion (World Health Organization 1998); when applied to the most recent estimate of maternal deaths worldwide (i.e. 515,000 for the year 1995; World Health Organization 2001), this percentage corresponds to about 67,000 deaths annually. In addition, unsafe abortion is associated with considerable morbidity. For instance, studies indicate that at least one in five women who have an unsafe abortion suffer a reproductive tract infection as a result. Some of these are serious infections, leading to infertility (World Health Organization 1998). Where access to abortion services is legally restricted, or where the law provides for abortion on many grounds but services are not fully available or are of poor quality, women who have money are nonetheless often able to buy medically competent services from the private sector. But many other women who have unwanted pregnancies are at particular risk of unsafe abortion. They include women who are poor, live in isolated areas, are in vulnerable circumstances (such as refugees or internally displaced women) or are adolescents, especially those who are not married. These women have less access to reproductive health information and services, they are often highly vulnerable to sexual coercion and violence, they may delay seeking abortion, and they are thus more likely to have to rely on unsafe abortion methods and unskilled providers (Bott 2001, Gardner and Blackburn 1996, Mundigo and Indriso 1999).

Almost all the deaths and complications from unsafe abortion are preventable. Procedures and techniques for early induced abortion are simple and safe. When performed by trained health care providers with proper equipment, correct technique and sanitary standards, abortion is one of the safest medical procedures. In countries where women have access to safe services, their likelihood of dying as a result of an abortion performed with modern methods is no more than one per 100,000 procedures (Alan Guttmacher Institute 1999). In developing countries, the risk of death following complications of unsafe abortion procedures is several hundred times higher than that of an abortion performed professionally under safe conditions (World Health Organization 1998). Properly provided services for early abortion save women's lives and avoid the often substantial costs of treating preventable complications of unsafe abortion (Fortney 1981, Tshibangu et al. 1984, Figa-Talamanca et al. 1986, Mpangile et al. 1999).

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Legal, policy and contextual considerations

In almost all countries, the law permits abortion to save the woman's life (Figure 1.1). In more than three-fifths of countries, abortion is also allowed to preserve the physical and mental health of the woman and, in about 40 per cent, abortion is permitted in cases of rape or incest or fetal impairment. One-third of countries allow abortion on economic or social grounds, and at least

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Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

one-quarter allow abortion on request (United Nations Population Division 1999). Thus, virtually all countries should have accessible and safe services in place to provide abortion where the law permits. Nonetheless, in many circumstances where women are legally entitled to have an abortion, safe services are not available for a range of reasons. These include health system problems such as a lack of trained providers or their concentration in urban areas, negative provider attitudes, use of inappropriate or outdated methods of inducing abortion, lack of authorisation for providers or facilities, lack of knowledge of the law or lack of application of the law by providers, complex regulatory requirements, or lack of resources. Broader policy and social factors, such as regulatory or legal requirements; lack of public information about the law and women's rights under the law; lack of awareness about facilities providing abortion or the need to obtain abortion early in pregnancy; family attitudes; stigmatisation and fears

about privacy and confidentiality; and the perceived quality of care provided, must also be addressed if safe, legal services are to be accessible. Health professionals at all levels have ethical and legal obligations to respect women's rights. Working together with the Ministries of Health and Justice, and their professional associations, they can help to clarify the circumstances where abortion is not against the law. They should understand and apply their national law related to abortion, and contribute to the development of regulations, policies and protocols to ensure access to quality services to the extent permitted by law and respecting women's rights to humane and confidential treatment. Ready access to early safe abortion significantly reduces high rates of maternal mortality and morbidity; it prevents the costs currently imposed by unsafe abortion on health systems; it provides care for women who clearly are not yet well enough served by family planning programmes or for whom contraception has failed.

Figure 1.1 Grounds on which abortion is permitted ­ percentage of countries To save a woman's life To preserve physical health To preserve mental health Rape or incest Fetal impairment Economic or social reasons On request 0%

Source: United Nations Population Division 1999 Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

98% 63% 62% 43% 39% 33% 27% 100%

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The challenge making safe services available

Making abortion safe and accessible to the full extent of the law requires training health personnel so that they are conversant with national laws and regulations as well as with technical procedures, ensuring equipment and supplies, and designing protocols, regulations and policies that promote access to quality abortion services. The chapters which follow make recommendations on each of these, based on available evidence and experience, and guided by the principles agreed upon in ICPD, FWCW, ICPD+5 and FWCW+5, and in conformity with international human rights. Given that abortion is legal for certain indications in most countries of the world, there is considerable scope in almost every country ­ both developed and developing ­ to apply the guidance put forth in this document. Chapter 2, "Clinical care for women undergoing abortion", reviews clinical aspects of providing high-quality abortion services, including diagnosis of pregnancy, provision of information and counselling, selection and provision of an appropriate abortion method, and care after abortion. It describes recommended abortion methods and the characteristics that influence their safety, efficacy and optimal use.

Chapter 3, "Putting services in place", provides guidance on the essential elements needed to put good-quality, legal abortion services in place. Topics discussed include needs assessment, national norms and standards, elements of care at each level of the health system, ensuring provider skills and performance, certification and licensing, monitoring and evaluation, and financing. Chapter 4, "Legal and policy considerations", lays out a policy framework to ensure access to safe abortion services to the full extent of the law. Topics include legal grounds for abortion, creating an enabling policy context and removing unnecessary barriers to care. Further resources and readings are included in Annex 1, to which readers can refer for more in-depth information on topics discussed in the monograph. Annex 2 provides the relevant text from international consensus documents, and Annexes 3 and 4 provide further details about equipment needed and about contraception after abortion, respectively.

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Chapter 1 ­ Safe abortion services: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

References

Alan Guttmacher Institute. (1999) Sharing responsibility: women, society & abortion worldwide. New York and Washington DC, The Alan Guttmacher Institute. Bongaarts J and Westoff CF. (2000) The potential role of contraception in reducing abortion. Studies in Family Planning 31:193-202. Bott S. (2001) Unwanted pregnancy and induced abortion among adolescents in developing countries: findings from WHO case studies. In: Puri CP and Van Look PFA (eds). Sexual and reproductive health: recent advances, future directions. New Delhi, New Age International (P) Limited, Volume 1, 351-366. Figa-Talamanca I, Sinnathuray TA, Yusof K, Fong CK, Palan VT, Adeeb N, Nylander P, Onifade A, Akin A and Bertan M. (1986) Illegal abortion: an attempt to assess its costs to the health services and its incidence in the community. International Journal of Health Services 16:375-389. Fortney JA. (1981) The use of hospital resources to treat incomplete abortions: examples from Latin America. Public Health Reports 96:574-579. Gardner R and Blackburn R. (1996) People who move: new reproductive health focus. Population Reports Series J, No. 45. Mpangile GS, Leshabari MT and Kihwele DJ. (1999) Induced abortion in Dar es Salaam, Tanzania: the plight of adolescents. In: Mundigo AI and Indriso C. (eds). Abortion in the developing world. New Delhi, Vistaar Publications for the World Health Organization, pp. 387-403. Mundigo AI and Indriso C. (eds). (1999) Abortion in the developing world. New Delhi, Vistaar Publications for the World Health Organization.

Trussell J. (1998) Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart F, Cates W Jr, Stewart GK, Guest F and Kowal D (eds). Contraceptive technology (17th revised edition). New York, Ardent Media Inc., pp. 779-844. Tshibangu K, Ntabona B, Liselele-Bolemba L and Mbiye K. (1984) Avortement clandestin, problème de santé publique à Kinshasa. [Illicit abortion, a public health problem in Kinshasa (Zaire)] Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (Paris) 13:759-763. United Nations. (1995) Report of the International Conference on Population and Development, Cairo, 5-13 September 1994. New York, United Nations. (Sales No. 95.XIII.18) United Nations. (1996) Report of the Fourth World Conference on Women, Beijing, 4-15 September 1995. New York, United Nations. (Sales No. 96.IV.13) United Nations. (1999) Key actions for the further implementation of the Programme of Action of the International Conference on Population and Development. New York, United Nations. (A/S-21/5/Add.1) United Nations Population Division. (1999) World abortion policies 1999. New York, United Nations. Population Division (ST/ESA/SER.A/178). United Nations Population Division. (2002) World contraceptive use 2001. New York, United Nations (Sales No. E.02.XIII.7). World Health Organization. (1992) The prevention and management of unsafe abortion. Report of a Technical Working Group. Geneva, World Health Organization. (WHO/MSM/92.5) World Health Organization. (1998) Unsafe abortion: global and regional estimates of incidence of and mortality due to unsafe abortion with a listing of available country data. Geneva, World Health Organization. (WHO/RHT/MSM/97.16) World Health Organization. (2001) Maternal mortality in 1995: estimates developed by WHO, UNICEF, UNFPA. Geneva, World Health Organization. (WHO/RHR/01.9)

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Clinical care for women Chapter 2 undergoing abortion

Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

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Chapter 2 Summary

Pre-abortion care Determining the length of pregnancy is a critical factor in selecting the most appropriate abortion method. Bimanual pelvic examination and recognition of other symptoms of pregnancy is usually adequate. Laboratory or ultrasound testing may be used for confirmation. In areas where anaemia is prevalent, measuring haemoglobin or haematocrit levels will enable prompt response in case of complications potentially requiring blood transfusion. Routine use of antibiotics at the time of abortion reduces the post-procedural risk of infection. However, abortion should not be denied where prophylactic antibiotics are not available. Complete, accurate and easy-to-understand information about the procedure and what to expect during and afterwards must be given to the woman, as well as voluntary counselling about options available to her to help her make informed decisions. Methods of abortion The following methods are preferred for early (first trimester) abortion: - Manual or electric vacuum aspiration, for up to 12 completed weeks since the woman's last menstrual period; - Medical method of abortion ­ a combination of mifepristone followed by a prostaglandin such as misoprostol or gemeprost, for up to 9 completed weeks since last menstrual period. Misoprostol is the prostaglandin of choice for most settings since it is cheap and does not require refrigeration. Dilatation and curettage (D&C) should be used only where vacuum aspiration or medical methods of abortion are not available. For pregnancies of more than 12 completed weeks since the woman's last menstrual period, the following methods are preferred: - Dilatation and evacuation (D&E), using vacuum aspiration and forceps; - Mifepristone followed by repeated doses of a prostaglandin such as misoprostol or gemeprost; - Prostaglandins alone (misoprostol or gemeprost), in repeated doses.

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Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

Cervical preparation before surgical abortion is recommended for durations of pregnancy over 9 completed weeks for nulliparous women, for women younger than 18 years old, and for all women with durations of pregnancy over 12 completed weeks. Medication for pain management should always be offered. In most cases, analgesics, local anaesthesia and/or mild sedation supplemented by verbal support are sufficient. Local anaesthesia, such as lidocaine injected around the cervix, should be used to alleviate women's discomfort where mechanical cervical dilatation is required for surgical abortion. General anaesthesia is not recommended for abortion as it has been associated with higher rates of complications than local anaesthesia. Universal precautions for infection control should be used, as with the care of all patients at all times, to reduce the risk of transmission of bloodborne infections including HIV.

Follow-up For surgical abortion, women can leave the health care facility as soon as they feel able and their vital signs are normal. For surgical methods, women should ideally have a follow-up visit 7-10 days after the procedure. For medical methods of abortion, if abortion is not complete before they leave the health facility, women should return after 10-15 days for confirmation that the abortion has been completed. Before they leave the health care facility, all women should receive information on contraception and, for those who want them, contraceptives or referral to contraceptive services. Women should receive oral and written instructions about how to care for themselves after leaving the health care facility, about how much bleeding to expect, and about recognizing complications and how to seek help for them.

Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

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Definitions used in this document Surgical methods of abortion - Use of transcervical procedures for terminating pregnancy, including vacuum aspiration, dilatation & curettage (D&C), and dilatation and evacuation (D&E). Duration of pregnancy - The number of completed days or weeks since the first day of the woman's last normal menstrual period.

Medical methods of abortion - Use of pharmacological drugs to terminate pregnancy. Sometimes the term "non-surgical abortion" is also used.

Menstrual regulation - Early uterine evacuation without laboratory or ultrasound confirmation of pregnancy for women who report delayed menses.

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Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

1

Pre-abortion care

The first steps in providing abortion care are to establish that the woman is indeed pregnant and, if so, to estimate the duration of the pregnancy and confirm that the pregnancy is intrauterine. The risks associated with induced abortion, though small when abortion is properly performed, increase with the duration of pregnancy (Grimes and Cates 1979). Thus, determination of the length of pregnancy is a critical factor in selecting the most appropriate abortion method. Every health service delivery point should have staff trained and competent to take the woman's history and perform a bimanual pelvic examination. Health centres not staffed and equipped to provide induced abortion must be able to refer women promptly to the nearest services. Staff should also be competent to offer counselling to help the woman consider her options (see section 1.10.1). 1.1 PATIENT HISTORY

their first postpartum menses. Some women may experience non-menstrual bleeding in early pregnancy, and this can be a cause of missing or misdating pregnancy. Other symptoms that women commonly report in early pregnancy include breast tenderness and engorgement, nausea sometimes accompanied by vomiting, fatigue, changes in appetite and increased frequency of urination. 1.2 PHYSICAL EXAMINATION

Health providers must confirm pregnancy and estimate its duration by a bimanual pelvic examination. While many health workers have been trained to assess the length of pregnancy in order to provide prenatal care, many are not experienced in diagnosing very early pregnancy or accurately estimating length of pregnancy during the first trimester. Hence, additional training is often required for staff who are to provide abortion services (see Chapter 3). Signs of pregnancy detectable during a bimanual pelvic examination as early as 6 to 8 weeks of pregnancy include softening of the cervical isthmus and softening and enlargement of the uterus. A uterus in a pregnant woman that is smaller than expected could be due to a pregnancy that is less advanced than estimated from the date of LMP, an ectopic pregnancy, or a missed abortion; and a larger than expected uterus may indicate a pregnancy that is more advanced than calculated from the date of LMP, a multiple pregnancy, the presence of uterine fibroids, or a molar pregnancy.

Most women begin to suspect that they are pregnant when a menstrual period is late. The woman should be asked about the first day of her last menstrual period (LMP), i.e. the first day of bleeding and whether the menses was normal. Women may experience amenorrhoea for reasons other than pregnancy, however, and some women who are pregnant may not report having missed a period. For example, women who are breastfeeding may become pregnant before

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1

Pre-abortion care continued

During the physical examination, the health worker should also assess whether the uterus is anteverted, retroverted or otherwise positioned in a way that might affect assessment of the length of pregnancy or complicate a surgical abortion. Providers should be trained to recognize signs of sexually transmitted infections (STIs) and other reproductive tract infections (RTIs) as well as other conditions such as anaemia or malaria that may require additional service procedures or referral for medical attention. In cases where serious cervical pathology is observed, the woman should be referred to appropriate facilities for further examination. 1.3 LABORATORY TESTING

Tests for ABO and Rhesus (Rh) blood group typing should be provided where feasible, especially at higher-level referral centres, in case of complications that might require blood transfusion (see 2.5.2.3 below). 1.4 ULTRASOUND SCANNING

In most cases, providers only require the information obtained from the woman's history and from a physical examination to confirm the pregnancy and estimate its length. Laboratory testing for pregnancy may not be needed, unless the typical signs of pregnancy are not clearly present and the provider is unsure whether the woman is pregnant. However, obtaining such tests should not hinder or delay uterine evacuation. Measuring haemoglobin or haematocrit levels to detect anaemia in areas where it is prevalent, enables the provider to initiate treatment and be prepared if haemorrhage occurs at the time of or following the abortion procedure.

Ultrasound scanning is not necessary for the provision of early abortion (RCOG 2000). Where it is available, ultrasound can aid the detection of ectopic pregnancies beyond about 6 weeks of pregnancy. Some providers find the technology helpful before or during abortion procedures at later stages of pregnancy. Where ultrasound is used, service delivery sites should, if possible, provide separate areas where women seeking abortion can be scanned, away from those receiving prenatal care. 1.5 PRE-EXISTING CONDITIONS

In addition to confirming and estimating the duration of pregnancy, health workers should obtain a full medical history and assess other factors that may affect the provision of abortion. These include: bleeding disorders, allergies to any medication to be used during the abortion, and information about any drugs the woman is taking that could interact with those to be used during the procedure. From a clinical point of view, presence of HIV infection in a woman undergoing abortion requires the same precautions as for other medical/surgical interventions (see 2.5.1 below). If the woman is known to be HIVpositive, she may need special counselling (see 1.10.1).

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Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

1.6

REPRODUCTIVE TRACT INFECTIONS (RTIs)

The presence of infection in the lower reproductive tract at the time of abortion is a risk factor for post-procedural RTIs (Penney et al. 1998). The routine use of antibiotics at the time of abortion has been reported to reduce the post-procedural risk of infection by half (Sawaya et al. 1996). However, where antibiotics are not available for prophylactic use, abortion can be performed. In any case, strict observation of cleaning and disinfection procedures plays an essential role in preventing post-procedural infection (see section 2.5.1). If clinical signs indicate infection, the woman should be treated immediately with antibiotics and abortion can then be carried out. Where laboratory testing for RTIs is routinely performed, and if there are no visible signs of infection, abortion should not be delayed to wait for the test results. 1.7 ECTOPIC PREGNANCY

transfer the woman as soon as possible to a facility that has the capacity to confirm diagnosis and initiate treatment (see World Health Organization 2000a for treatment details). It should be noted that it is more difficult to diagnose an ectopic pregnancy during and after medical methods of abortion due to similarity of symptoms. Therefore, if medical methods of abortion are being used without prior confirmation that the pregnancy is intrauterine, and the woman has severe and intensifying pain after the procedure, she should undergo assessment for ectopic pregnancy. 1.8 RH-ISOIMMUNISATION

Ectopic pregnancy can be life-threatening. Signs that might indicate extrauterine pregnancy include uterine size smaller than expected for the estimated length of pregnancy and lower abdominal pain, especially if accompanied by vaginal bleeding and spotting, dizziness or fainting, pallor and, in some women, an adnexal mass. If ectopic pregnancy is suspected, it is essential to confirm diagnosis immediately and initiate treatment or

Passive immunisation of all Rh-negative women with Rh-immunoglobulin within 72 hours after abortion was recommended in the USA in 1961 (Finn et al. 1961), yet there is still no conclusive evidence about the need for this measure after first-trimester induced abortion. Where Rh-immunoglobulin is routinely provided in the facility to Rh-negative women, it should be administered at the time of the abortion procedure. For women using medical methods of abortion, administration of Rh-immunoglobulin has been recommended at the time of the prostaglandin administration (Urquhart and Templeton 1990).

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1

1.9

Pre-abortion care continued

CERVICAL CYTOLOGY

Some sites may also offer women cervical smears and other reproductive health services. An abortion request may be an opportunity for assessing cervical cytology of women, especially in settings where there is a high prevalence of cervical cancer and STIs. However, accepting such services must never be a condition for a woman to obtain an abortion and these services are not required in order to perform abortion safely. 1.10 INFORMATION AND COUNSELLING

to make a decision, even if it means returning to the clinic later. However, the greater safety and effectiveness of early abortion should be explained. The health worker should also provide information for women who decide to carry the pregnancy to term and/or consider adoption, including referral as appropriate. In some circumstances the woman may be under pressure from her partner or other family members to have an abortion. Unmarried adolescents and women who are HIV-infected may be particularly vulnerable to such pressure. All women who are known to be HIV-infected need to know the risks of pregnancy to their own health and the risks of transmission of the virus to their infants. They also need to know about treatments available for themselves and for preventing transmission to infants in order to make an informed decision about whether to continue with the pregnancy or have it terminated, where permitted by law. They may also request additional counselling (World Health Organization 1999). If health workers suspect coercion, they should talk with the woman alone, or refer her for additional counselling. If staff know or suspect that the woman has been subjected to sexual violence or abuse, they should refer her for other counselling and treatment services as appropriate. Managers should ensure that all staff know about the availability of such resources in the health system and the community (see Chapter 3).

The provision of information is an essential part of good-quality abortion services. Information must be complete, accurate and easy to understand, and be given in a way that respects the woman's privacy and confidentiality. Chapter 3 gives details about training and other provider requirements related to provision of information and counselling, including ethical standards. 1.10.1 Decision-making counselling Counselling can be very important in helping the woman consider her options and ensure that she can make a decision free from pressure. Counselling should be voluntary, confidential and provided by a trained person. If the woman opts for abortion, the health worker should explain any legal requirements for obtaining it. The woman should be given as much time as she needs

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Chapter 2 ­ Clinical care for women undergoing abortion Safe Abortion: Technical and Policy Guidance for Health Systems

1.10.2 Information on abortion procedures At a minimum, a woman must be given information on: what will be done during and after the procedure; what she is likely to experience (e.g. menstrual-like cramps, pain and bleeding); how long the procedure will take; what pain management can be made available to her; risks and complications associated with the method; when she will be able to resume her normal activities, including sexual intercourse; and follow-up care. If a choice of abortion methods is available, providers should be trained to give women clear information about which methods are appropriate, based on the length of pregnancy and the woman's medical condition and potential risk factors.

1.10.3 Contraceptive information and services Provision of contraceptive information and services is an essential part of abortion care as it helps the woman avoid unintended pregnancies in the future. Every woman should be informed that ovulation can return as early as about two weeks after abortion (Cameron and Baird 1988), putting her at risk of pregnancy unless an effective contraceptive method is used. She should be given accurate information to assist her in choosing the most appropriate contraceptive method to meet her needs. If the woman is seeking an abortion following what she considers to be a contraceptive failure, the provider should discuss whether the method may have been used incorrectly and how to correct its use, or whether it may be appropriate for her to change to a different method (for discussion on specific methods, see section 3.2 and Annex 4). The final selection of a method, however, must be the woman's alone. A woman's acceptance of a contraceptive method must never be a precondition for providing her an abortion.

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Figure 2.1 Methods of abortion Completed weeks since last menstrual period 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Preferred methods Vacuum aspiration (manual/electric) (by specially trained providers)

Dilatation and evacuation

Mifepristone and misoprostol (or gemeprost)

(under investigation)

Mifepristone and repeated doses of misoprostol or gemeprost

Vaginal prostaglandins (repeated doses) Other methods Dilatation and curettage

Hypertonic solutions

Intra/extra-amniotic prostaglandins

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Methods of abortion

SUMMARY Figure 2.1 summarises the methods of abortion that are the most appropriate at different stages of pregnancy, based on established protocols used worldwide. It is indicative rather than prescriptive with regard to the time limits. For example, most trained providers can safely undertake vacuum aspiration up to 12 completed weeks of pregnancy, while others with special training, sufficient experience and access to appropriately-sized cannulae can use this procedure safely up to 15 completed weeks (RCOG 2000). The availability of safe and effective medical methods of inducing abortion remains limited at present. However, rapid development and ongoing research may lead to their wider introduction in the near future. The use of these drugs is therefore discussed in order for programme planners and managers to prepare for their eventual introduction in a systematic manner. Methods up to 12 completed weeks since last menstrual period The preferred methods are manual or electric vacuum aspiration, or medical methods using a combination of mifepristone followed by a prostaglandin. Mifepristone followed by a prostaglandin has been shown safe and effective up to 9 completed weeks of pregnancy, and the safety and effectiveness of the regimen between 9 and 12 completed weeks is under investigation.

The use of medical methods of abortion requires the back-up of vacuum aspiration on site or through referral in case of failed or incomplete abortion. Dilatation and curettage (D&C) should be used only where none of the above methods are available. Health managers and policy-makers should make all possible efforts to replace sharp curettage (D&C) with vacuum aspiration. Methods after 12 completed weeks since last menstrual period A number of situations give rise to the need for abortion services later in pregnancy, and all levels of the health system should be able to refer women to centres that have the capacity to perform later abortions safely. The diagnosis of fetal abnormalities usually does not occur until after 12 weeks of pregnancy, and serious cardiovascular disease or cancer requiring aggressive treatment for the woman, for example, can necessitate later abortion for medical reasons. Some women, particularly adolescents, cannot easily obtain early care or they delay accessing services. This may be due to the woman's lack of knowledge about conditions under which abortion is permitted, lack of information about or access to health care services, financial constraints, inability to recognize the signs of pregnancy, irregular menses, initial ambivalence about having an abortion, health concerns that arise after the first trimester, family conflict or a change in life circumstances that makes a previously wanted pregnancy no longer feasible.

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2

Methods of abortion continued

The preferred medical method for abortions after 12 completed weeks since last menstrual period is mifepristone followed by repeated doses of a prostaglandin such as misoprostol or gemeprost. The preferred surgical method is dilatation and evacuation (D&E), using vacuum aspiration and forceps. 2.1 CERVICAL PREPARATION

Cervical preparation (or priming) using osmotic dilators or pharmacologic agents is commonly used in some countries before first-trimester surgical abortions because it makes the abortion procedure quicker and easier to perform and reduces the incidence of common immediate complications in abortions performed after 9 completed weeks of gestation (World Health Organization 1997). Cervical priming before surgical abortion is especially beneficial for certain women, such as those with cervical anomalies or previous surgery, young women and those with advanced pregnancies, who have a higher risk of cervical injury or uterine perforation that may cause haemorrhage (Grimes et al. 1984, Schulz et al. 1983). However, cervical preparation has some disadvantages, including the extra cost and time required. It is therefore recommended for durations of pregnancy over 9 completed weeks for nulliparous women, for women younger than 18 years old and for all women with durations of pregnancy over 12 completed weeks (RCOG 2000, World Health Organization 1997).

Recent research suggests vaginal administration of 400µg misoprostol 3 to 4 hours before the operation has been found to be effective (Singh et al. 1998). Oral administration of 400µg misoprostol 3 to 4 hours before the procedure is also appropriate for cervical priming (Ngai et al. 1999). Other effective regimens are 200mg mifepristone taken orally 36 hours before the procedure (World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 1994) or 1mg gemeprost vaginally administered 3 hours before the procedure (Henshaw and Templeton 1991). 2.2 PAIN MANAGEMENT

Most women report some degree of pain with abortion. The factors associated with pain during surgical abortion with local anaesthesia have been evaluated in several observational studies. The degree of the pain varies with the age of the woman, length of pregnancy, amount of cervical dilatation and the fearfulness of the woman (Smith et al. 1979). Prior vaginal delivery has been found to be a decreasing factor (Borgatta and Nickinovich 1997). Time interval less than 2 minutes between administration of the local anaesthetic and the beginning of the procedure, lack of choice between local and general anaesthesia, and a history of frequent use of analgesics have also been reported to contribute to increased pain (Donati et al. 1996). Providing adequate pain management does not require a large investment in drugs, equipment or training. Neglecting this important element needlessly increases women's anxiety and discomfort and seriously compromises quality of care.

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Counselling and sympathetic treatment is likely to reduce women's fears and perceptions of pain (Solo 2000). The person performing the procedure and other staff present should be friendly and reassuring. Where feasible, and if the woman wishes, it may also be helpful for the woman's husband or partner, a family member or friend to remain with her during the procedure. However, these approaches should not be seen as a replacement for medical pain alleviation. 2.2.1 Medication for pain Medication for pain management should always be offered. Three types of drugs, either singly or in combination, are used to manage pain during abortion: analgesics, which alleviate the sensation of pain; tranquillizers, which reduce anxiety; and anaesthetics, which numb physical sensation. In most cases, analgesics, local anaesthesia and/or mild sedation supplemented by verbal support, are sufficient. Most of these drugs are comparatively inexpensive. Non-narcotic analgesics included on WHO's Model List of Essential Medicines such as non-steroidal anti-inflammatory agents are usually sufficient to reduce pain associated with both surgical and medical methods of abortion, including cramping (Suprapto and Reed 1984, Matambo et al. 1999). Paracetamol was found to be ineffective to relieve post-procedural pain in three randomized control trials (Cade and Ashley 1993, Hein et al. 1999, Dahl et al. 2000).

For surgical abortion, preoperative administration of tranquillizers, such as diazepam can reduce fear and induce relaxation, making the procedure easier for both the woman and the provider. Such drugs can cause amnesia, which some women may want, but they may also induce drowsiness and delay ambulation. Supplemental use of narcotic analgesics may also be appropriate, though the possibility of complications such as respiratory depression means that resuscitation capability and narcotic reversal agents must be available. 2.2.2 Anaesthesia Where mechanical cervical dilatation is required for surgical abortion, a paracervical block, using a local anaesthetic such as the rapidly acting lidocaine, injected beneath the cervical mucosa at the "four quadrant" positions around the cervix should be used to alleviate women's discomfort. Advantages of using local rather than general anaesthesia include a faster recovery time and the fact that the woman remains conscious and hence is able to alert the provider to problems that might arise. Injection of local anaesthetic must be done skillfully, to avoid intravenous introduction of the drug. The use of local anaesthesia with vacuum aspiration has been proved to be safe and effective (Thonneau et al. 1998).

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Methods of abortion continued

General anaesthesia is not recommended for abortion and increases the clinical risks (Lawson et al. 1994, MacKay et al. 1985, Osborn et al. 1990). It has been associated with higher rates of haemorrhage than local anaesthesia (Grimes and Cates 1979). Use of general anaesthesia increases costs for both the health care facility and the woman, particularly as some hospital policies unnecessarily require women receiving it to stay overnight. Nevertheless, some women prefer general anaesthesia, and its use may also be preferable from the provider's perspective during difficult procedures. Any facility that offers general anaesthesia must have the specialized equipment and staff skilled to administer it and to handle any complications. 2.3 SURGICAL ABORTION

Vacuum aspiration involves the evacuation of the contents of the uterus through a plastic or metal cannula, attached to a vacuum source. Electric vacuum aspiration (EVA) employs an electric vacuum pump. With manual vacuum aspiration (MVA), the vacuum is created using a hand-held, hand-activated, plastic 60ml aspirator (also called a syringe). Available aspirators accommodate different sizes of plastic cannulae, ranging from 4 to at least 12mm in diameter. Some cannulae and most aspirators are re-usable after being cleaned and high-level disinfected or sterilized. Foot-operated mechanical pumps are also available. Depending on the duration of pregnancy, abortion with vacuum aspiration takes from 3 to 10 minutes to complete and can be performed on an outpatient basis, using analgesics and/or local anaesthesia. In very early pregnancy, the cannula may be inserted without prior dilatation of the cervix. Usually, however, dilatation using mechanical or osmotic dilators, alone or in combination with a prostaglandin, or cervical priming with pharmacological agents such as mifepristone or a prostaglandin (misoprostol or gemeprost), is required before insertion of the cannula. Most women who have first-trimester abortions with local anaesthesia feel well enough to leave the health care facility after observation for about 30 minutes in a recovery room. Longer recovery periods are generally needed for abortions performed later in pregnancy and when sedation or general anaesthesia has been used.

2.3.1 Vacuum aspiration The preferred surgical technique for abortion up to 12 completed weeks of pregnancy is vacuum aspiration. Some providers, depending on their training and experience and the particular case, are able to use vacuum aspiration up to 15 completed weeks. The high efficacy of vacuum aspiration has been well established in several randomized control trials. Complete abortion rates between 95% and 100% are reported (Greenslade et al. 1993). Electric and manual vacuum technologies appear to be equally effective (Westfall et al. 1998).

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Vacuum aspiration is a very safe procedure. A study of 170,000 first trimester abortions carried out in New York City, USA (the majority by vacuum aspiration) reported that less than 0.1% of the women experienced serious complications requiring hospitalization (Hakim-Elahi et al. 1990). Though rare, complications with vacuum aspiration can include pelvic infection, excessive bleeding, cervical injury, incomplete evacuation, uterine perforation, anaesthesia complications and ongoing pregnancy (Grimes and Cates 1979). Abdominal cramping or pain and menstrual-like bleeding are side-effects of any abortion procedure. 2.3.2 Dilatation and curettage Dilatation and curettage (D&C), also known as "sharp curettage", involves dilating the cervix with mechanical dilators or pharmacological agents and using sharp metal curettes to scrape the walls of the uterus. Dilatation and curettage is less safe than vacuum aspiration (Cates et al. 2000) and considerably more painful for women (Grimes et al. 1977). Vacuum aspiration has replaced D&C in routine use in most industrialized countries and in many others. The rates of major complications of D&C are two to three times higher than those of vacuum aspiration (Grimes and Cates 1979). A randomized controlled trial comparing D&C with vacuum aspiration found that, up to 10 weeks since LMP, vacuum aspiration is quicker and associated with less blood loss than D&C (Lean et al. 1976).

Table 2.1 summarizes the requirements for vacuum aspiration and D&C. Where D&C is currently practiced, all possible efforts should be made to replace it with vacuum aspiration, to improve the safety and quality of care. Where no abortion-related services are currently offered, vacuum aspiration should be introduced rather than D&C. At sites where D&C continues to be used, managers must ensure that proper pain management procedures are followed, and that staff are well-trained and receive adequate supervised clinical practice to maintain their skills. 2.3.3 Dilatation and evacuation Dilatation and evacuation (D&E) is used from about 12 completed weeks of pregnancy. It is the safest and most effective surgical technique for later abortion where skilled, experienced providers are available (RCOG 2000). D&E requires preparing the cervix with mifepristone, a prostaglandin such as misoprostol, or laminaria or similar hydrophilic dilator; dilating the cervix; and evacuating the uterus using electric vacuum aspiration with 14-16mm diameter cannulae and forceps. Depending on the duration of pregnancy, adequate dilatation can require anything from two hours to a full day. Many providers find the use of ultrasound helpful during D&E procedures, but it is not essential.

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Table 2.1 Requirements for vacuum aspiration and dilatation & curettage Characteristic Location Vacuum Aspiration Examination room, general operating room or ob/gyn operating room Mild sedation, analgesia, and/or local anaesthesia Gynaecologist, trained general physician, trained mid-level provider Dilatation & Curettage General operating room or ob/gyn operating room Heavy or mild sedation, analgesia, and/or local anaesthesia Gynaecologist, trained general physician

Pain management

Level of provider

Adapted from Greenslade et al. 1993

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Methods of abortion continued

A randomized controlled trial comparing D&E with intra-amniotic instillation of the older prostaglandin PGF2 found D&E to be faster, safer and more acceptable at least through about 18 weeks of pregnancy (Grimes et al. 1980). D&E has not been compared to the newer medical methods such as mifepristone with repeated doses of misoprostol. If providers do not have adequate supervised training and a case-load sufficient to maintain their skills in D&E, then medical methods should be used. A D&E procedure can usually be performed with only a paracervical block and mild analgesia, and the procedure can thus be performed on an outpatient basis. However, sites offering this procedure should be equipped and have personnel trained to administer

conscious sedation or deep sedation, if required. General anaesthesia is not required and can increase risk (see 2.2.2 above). A D&E procedure usually takes no more than 30 minutes to perform. Clinic staff and women undergoing the procedure should expect more post-operative discharge, including bleeding, than after a first-trimester abortion. Staff should also be trained to provide specialized counselling for second-trimester abortion patients. 2.3.4 Other surgical methods of abortion for use in later pregnancy Major operations should not be used as primary methods of abortion. Hysterotomy has no role in contemporary abortion practice since its morbidity, mortality and cost are markedly higher than with D&E or medical methods of abortion. Similarly, hysterectomy should not be used except for women with conditions that would warrant the operation independently.

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2.3.5

Tissue examination following surgical abortion After surgical methods of abortion, immediate examination of the products of conception is important to exclude the possibility of ectopic pregnancy. With MVA, after about 6 completed weeks of pregnancy, trained providers can usually visually identify the products of conception, specifically chorionic villi. If the aspirate does not contain the expected products of conception, ectopic pregnancy should be suspected and the woman should undergo further evaluation, as discussed earlier (see 1.7). In addition, providers need to be alert to appearances suggestive of molar pregnancy. If the contents of the aspirate do not conform to the estimated length of pregnancy, health workers should consider the possibility of incomplete abortion. Routine analysis of the products of conception by a pathology laboratory is not essential. 2.4 MEDICAL METHODS OF ABORTION

of mifepristone followed by administration of a synthetic prostaglandin analogue, which enhances uterine contractions and helps expel the products of conception (Swahn and Bygdeman 1988). The effects of medical methods of abortion are similar to those associated with spontaneous abortion and include cramping and prolonged menstrual-like bleeding. Bleeding occurs for nine days on average but can last up to 45 days in rare cases (Creinin and Aubény 1999). Side-effects include nausea, vomiting and diarrhoea. Conditions that warrant caution with the use of mifepristone and a prostaglandin include chronic or acute adrenal or hepatic failure, bleeding disorders, heavy smoking and allergies to any of the drugs used. Mifepristone is not an effective treatment for ectopic pregnancy; suspicion of ectopic pregnancy demands further investigation and, if confirmed, immediate treatment (see World Health Organization 2000a for specifics on treatment). Medical methods of abortion have proved acceptable in several low-resource settings (Elul et al. 1999, Ngoc et al. 1999). However, the drugs, mifepristone in particular, are currently available in only a few developing countries. This may change in coming years, and programme managers should be aware of what would be required to introduce medical methods of abortion into health services.

Medical methods of abortion have been proved to be safe and effective (Ashok et al. 1998a, Peyron et al. 1993, Schaff et al. 1999, Spitz et al. 1998, Trussell and Ellertson 1999, Urquhart et al. 1997, Winikoff et al. 1997). The most widely used regimens rely on the antiprogestogen, mifepristone, which binds to progesterone receptors, inhibiting the action of progesterone and hence interfering with the continuation of pregnancy. Treatment regimens entail an initial dose

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Table 2.2 Commonly used mifepristone plus prostaglandin regimens Up to 9 completed weeks since LMP 200 mg mifepristone followed after 36-48 hours by 1.0 mg vaginal gemeprost or 800 µg vaginal misoprostol or 400 µg oral misoprostol up to 7 completed weeks After 12 completed weeks since LMP 200 mg mifepristone followed after 36-48 hours by 1 mg vaginal gemeprost (repeated every 6 hours up to maximum of 4 doses, and if necessary every 3 hours up to 4 additional doses) or 400 µg misoprostol orally every 3 hours up to 5 doses or 800 µg vaginal misoprostol followed by 400 µg oral misoprostol every 3 hours up to a maximum of 4 doses µg = micrograms mg = milligrams

2.4.1 Mifepristone and prostaglandin 2.4.1.1 Up to 9 completed weeks since last menstrual period Mifepristone with misoprostol or gemeprost has been proved to be highly effective, safe and acceptable for early first trimester abortions (RCOG 2000). Efficacy rates up to 98% are reported (Trussell and Ellertson 1999). Approximately 2 to 5% of women treated with the mifepristone and misoprostol regimen will require surgical intervention to resolve an incomplete abortion, terminate a continuing pregnancy, or control bleeding

(World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 2000). The original protocols for the use of mifepristone recommended an oral dose of 600mg mifepristone followed by 1mg of vaginal gemeprost after 36-48 hours. However, several studies have established that 200mg of mifepristone is the dosage of choice since it is as effective as 600mg (McKinley et al. 1993; World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 1993), and reduces costs.

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Misoprostol, a prostaglandin which has also been shown to be effective (RCOG 2000), is considerably cheaper than gemeprost, and does not require refrigeration. It is therefore the prostaglandin of choice for most countries. An oral dose of 200mg mifepristone followed by 800 µg misoprostol administered vaginally is an effective regimen (RCOG 2000). Vaginal misoprostol has been shown to be more effective and better tolerated than misoprostol given orally (El-Refaey et al. 1995). An oral dose of 400 µg of misoprostol is effective up to 7 completed weeks of pregnancy (World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 2000). Most protocols require that women take both mifepristone and prostaglandin under clinical supervision, involving a second visit to the health care facility two days after receiving mifepristone to take the prostaglandin. Women may leave the facility shortly after taking the mifepristone, after being told to expect bleeding and possible expulsion of products of conception, how to recognize complications and whom to contact if they should occur. Staff should be available on a 24-hour basis to respond to such situations. Following administration of the prostaglandin at the second visit, the standard observation period is 4-6 hours, during which up to 90% of women will expel the products of conception. Some women may require medication for cramps during this period (see 2.2.1 above). The approximately 10% of women who do not abort during the observation period should return to the health care facility about 2 weeks later to confirm that the abortion has been completed.

Protocols which allow the woman to leave the facility immediately after prostaglandin administration, call for explanation that she is likely to expel the products of conception at home or somewhere else without medical supervision. In this case, women should return to the health care facility about two weeks later to confirm completion of the abortion through a physical examination or laboratory test. Some investigators consider that the second visit to the facility for the prostaglandin is unnecessary and suggest that women be allowed to take the prostaglandin at home (Schaff et al. 1997). This approach has recently also been used in communities in Tunisia and Viet Nam and found to be acceptable to many women (Elul et al. 2001). However, the safety and appropriateness of this approach in different settings is still the subject of review. In the case of an incomplete or failed abortion, surgical abortion is required. Every facility offering medical methods of abortion must be able to ensure provision of vacuum aspiration in case the need arises. Such provision can be available on site or through an arrangement with another facility that performs vacuum aspiration. In all cases, health care providers must ensure that the woman can reach such services in case of an emergency.

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Methods of abortion continued

Women are more likely to be satisfied with the procedure if they have realistic expectations (Breitbart 2000). Hence, they need complete information about what is to be expected with, and the possible side-effects of, medical methods of abortion. Health workers should ensure that women understand the importance of complying with the protocol, especially if any of the drugs are self-administered, and that they know how to recognize, and what to do in case of, complications. 2.4.1.2 From 9 to 12 completed weeks since last menstrual period Mifepristone and misoprostol are also being investigated between 9 and 13 weeks of pregnancy (Ashok et al. 1998b). Initial positive findings need to be confirmed in order to establish the optimal regimens. 2.4.1.3 After 12 completed weeks since last menstrual period A regimen of oral mifepristone followed by repeated doses of misoprostol or gemeprost is safe and highly effective (RCOG 2000). An oral dose of 200mg mifepristone followed by 800µg misoprostol administered vaginally 36-48 hours later and further 400µg oral doses of misoprostol every three hours, to a maximum of four doses, has been found to be effective in 97% of cases (El-Refaey and Templeton 1995). An oral dose of 400µg of misoprostol every 3 hours up to 5 doses after 200mg mifepristone has also been used successfully (Ngai et al. 2000). A vaginally

administered dose of 1 mg gemeprost used after 200mg mifepristone and repeated if necessary every 6 hours up to four doses can also be used effectively (Ho et al. 1996). The treatment with gemeprost could continue with 1mg gemeprost every 3 hours for 4 additional doses if necessary (Gemzell-Danielsson and Ostlund 2000, Tang et al. 2001). 2.4.2 Misoprostol or gemeprost alone 2.4.2.1 Up to 12 completed weeks since last menstrual period Misoprostol alone has also been studied in terms of effectiveness and safety. Although no comparative studies have been conducted, available data suggest that the effectiveness of misoprostol alone is lower, the procedure lasts longer and is more painful with greater gastro-intestinal side-effects than the combined regimen with mifepristone (Bugalho et al. 2000). Because of the drug's wide availability and low cost and since in some settings its broader use has been reported to contribute to the decrease in the complications from unsafe abortion (Costa and Vessy 1993), the development of an optimal treatment regimen for the delivery of misoprostol alone is currently under investigation (Blanchard et al. 2000). There are concerns about the consequences of ongoing pregnancies with the use of misoprostol alone (Fonseca et al. 1991, Gonzalez et al. 1998, Schonhofer 1991, Orioli and Castilla 2000). Further research is needed to evaluate the possible teratogenicity of misoprostol.

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2.4.2.2 After 12 completed weeks since last menstrual period Misoprostol has been found to be up to 84% effective in inducing abortion within 24 hours with a variety of doses administered orally or vaginally (Dickinson et al. 1998, Wong et al. 1996), although it is not as rapid as when used in combination with mifepristone. Further research is needed to identify the optimal regimen for the use of misoprostol alone for pregnancies of more than 12 weeks. Vaginal administration of gemeprost alone is registered for termination of second-trimester pregnancy in several countries. The recommended dose is 1mg which is given every 3 hours up to 5 times during the first day and repeated the next day if necessary. With this treatment, 80% and 95% of women will abort within 24 and 48 hours, respectively (Thong et al. 1992). 2.4.3 Other medical abortion agents Methotrexate, which is a cytotoxic drug used to treat cancer, rheumatoid arthritis, psoriasis and some other conditions, has been used in combination with misoprostol as a medical method for early abortion (up to 7 completed weeks since LMP) in some countries where mifepristone has not been available. A recent randomized controlled trial reported an overall 92% success rate with 50mg of methotrexate followed by 800µg intravaginally administered misoprostol 6 or

7 days later. Success rate at day 15 was 83% (Creinin 2000). However, a WHO Toxicology Panel recommended against the use of methotrexate for inducing abortion, based on concerns about teratogenicity (UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction 1997). Although the actual risks are yet unknown, limb defects and skull and facial abnormalities in pregnancies that continued after failed attempts to induce abortion with methotrexate have been reported (Powell and Ekert 1971, Diniz et al. 1978, Feldkamp and Carey 1993). It is therefore recommended that services that wish to introduce medical methods of abortion use mifepristone and misoprostol, not methotrexate. Other agents are used to stimulate uterine contractions and induce abortion from 12 completed weeks since last menstrual period. They include intra-amniotic injection of hypertonic saline or hyperosmolar urea; intra- or extra-amniotic administration of ethacridine; parenteral, intra-amniotic or extra-amniotic administration of prostaglandin analogues; and intravenous or intramuscular administration of oxytocin (World Health Organization 1997). Most of these methods and routes of administration, however, are invasive and less safe than the newer medical methods.

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2

2.5

Methods of abortion continued

OTHER ISSUES RELATED TO ABORTION PROCEDURES

woman. It should be noted that use of auxiliary supplies such as sterile booties does not make a significant difference in infection rates while it increases costs. 2.5.1.2 Cleaning Detergents and hot water are adequate for the routine cleaning of floors, beds, toilets, walls, and rubber draw sheets. Following a spillage of body fluids, heavy-duty rubber gloves should be worn and as much body fluid as possible removed with an absorbent material. This can then be discarded in a leakproof container and later incinerated or buried in a deep pit. The area of spillage should be cleaned with a chlorine-based disinfectant and then thoroughly washed with hot soap and water. All soiled linen should be handled as little as possible, bagged at the point of collection and not sorted or rinsed in patient care areas. If possible, linen with large amounts of body fluid should be transported in leakproof bags. If leakproof bags are not available, the linen should be folded with the soiled parts inside and handled carefully, with gloves. 2.5.1.3 Safe disposal of waste contaminated with body fluids Solid waste that is contaminated with blood, body fluids, laboratory specimens or body tissue should be placed in leakproof containers and incinerated, or buried in a 7 foot deep pit, at least 30 feet away from a water source. Liquid waste such as blood or body fluid should be poured down a drain connected to an adequately-treated sewer or pit latrine.

2.5.1 Infection prevention and control Since abortion procedures and care involve contact with blood and other body fluids, all clinical and support staff in all facilities that provide these services should understand and apply universal precautions for infection prevention and control, for both their own and their patients' protection. Universal precautions are simple standards of infection control practices to be used in the care of all patients, at all times, to reduce the risk of transmission of bloodborne infections. They include: handwashing with soap and water before and after all procedures; use of protective barriers such as gloves, gowns, aprons, masks, goggles for direct contact with blood and other body fluids; safe disposal of waste contaminated with blood or other body fluids; proper handling of soiled linen; careful handling and disposal of "sharps"; and proper disinfection of instruments and other contaminated equipment (World Health Organization 2001). 2.5.1.1 Handwashing and use of protective barriers All staff should wash their hands thoroughly before coming into contact with the woman and immediately after any contact with blood, body fluids or mucous membranes. High-level disinfected or sterile gloves should be worn and replaced between contacts with different clients and between vaginal (or rectal) examinations of the same

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2.5.1.4 Safe handling and disposal of "sharps" The greatest hazard of HIV transmission in health care settings is through skin puncture with contaminated needles or "sharps". This also applies to hepatitis-B. Most "sharps" injuries involving such transmission are through deep injuries with hollow-bore needles. Such injuries frequently occur when needles are recapped, cleaned, disposed of, or inappropriately discarded. Although recapping needles is to be avoided whenever possible, sometimes recapping is necessary. When this is the case, a single-handed scooping method should be used. Puncture-resistant disposal containers must be available and readily accessible for the disposal of "sharps". These can be burned in a closed incinerator or buried in a deep pit. Added precautions to prevent "sharps" injuries include wearing gloves, having an adequate light source when treating women, locating "sharps" containers directly at the point of use, never discarding "sharps" in general waste, and keeping "sharps" out of the reach of children. Whenever possible, needle holders should be used when suturing. 2.5.1.5 Safe cleaning of equipment after use Immediately after use, all reusable surgical instruments used in abortion should be sent for cleaning and sterilization. Where central services for this are not available, or in resource-poor settings, the following procedures are recommended. The most important step to ensure proper final decontamination of instruments is physical cleaning. Instruments should immediately be washed with soap

under running water. All instruments should then be sterilized or disinfected with a high-level disinfectant. Sterilization kills all microorganisms, including bacterial endospores such as those that cause tetanus and gas gangrene. It is best achieved with pressurized steam [20 minutes at 121°C and 103.5-140kPa pressure] or gas (ethylene oxide) (Sopwith et al. 2001). High-level disinfection should be achieved by soaking instruments in a solution of hypochlorite bleach [5 minutes contact at 20-25°C with buffered hypochlorite (pH = 7-8) at a concentration of 5000ppm available chlorine], or fresh glutaraldehyde [5 hours contact at 20-25°C with a 2% activated alkaline formulation (pH = 7.5-9)] (Sopwith et al. 2001). High-level disinfection destroys all microorganisms including hepatitis-B virus and HIV but does not reliably kill bacterial endospores. The use of phenol or antiseptics will not achieve high-level disinfection. Instruments must be rinsed with sterile water after disinfection. Plastic instruments, such as most vacuum aspiration syringes and cannulae currently available, cannot be exposed to high heat for sterilization, since they will crack and melt. Unless there are specific instructions to the contrary, the cold methods of high-level disinfection described above should be used. Health workers should always refer to the instructions for use of all items being disinfected to ensure they are using the appropriate form of disinfection.

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2

Methods of abortion continued

2.5.2 Managing abortion complications When abortion is performed by appropriately trained personnel, complications are rare. Nevertheless, every service delivery site at every level of the health system should be equipped and have personnel trained to recognize abortion complications and to provide or refer women for prompt care, 24 hours a day (World Health Organization 1994). Facilities and skills required to manage abortion complications are similar to those needed to care for women who have had a miscarriage. 2.5.2.1 Incomplete abortion Incomplete abortion is uncommon with vacuum aspiration when the abortion is performed by a skilled provider. It is more common with medical methods of abortion. Signs and symptoms include vaginal bleeding, abdominal pain and signs of infection. It should also be suspected if, upon visual examination, the tissue aspirated during surgical abortion does not conform to estimated duration of pregnancy. Staff at every health care facility should be trained and equipped to treat incomplete abortion by re-evacuating the uterus with vacuum aspiration, paying attention to the possibility of haemorrhage or infection.

2.5.2.2 Failed abortion Failed abortion can occur in women who have undergone either surgical or medical methods of abortion. If, at the follow-up visit after either type of procedure, the pregnancy is continuing, termination of the pregnancy requires vacuum aspiration, or D&E for second-trimester pregnancies. 2.5.2.3 Haemorrhage Haemorrhage can result from retained products of conception, trauma or damage to the cervix or, rarely, uterine perforation. Depending on the cause, appropriate treatment may include re-evacuation of the uterus and administration of uterotonic drugs to stop the bleeding, intravenous fluid replacement, and, in severe cases, blood transfusion, laparoscopy or exploratory laparotomy. Because of the low incidence of haemorrhage using vacuum aspiration, it is not recommended to use oxytocics routinely, although they may be required with D&E. Prolonged menstrual-like bleeding is an expected effect of medical methods of abortion. Such bleeding rarely is heavy enough to constitute an emergency. However, every service-delivery site must be able to stabilize and treat or refer women with haemorrhage as quickly as possible.

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2.5.2.4 Infection Infection rarely occurs following properly performed abortion. Common symptoms include fever or chills, foul-smelling vaginal or cervical discharge, abdominal or pelvic pain, prolonged vaginal bleeding or spotting, uterine tenderness, and/or an elevated white blood cell count. When infection is diagnosed, health care staff should administer antibiotics and, if retained products of conception are a likely cause of infection, re-evacuate the uterus. Women with severe infections may require hospitalization. As discussed in section 1.6 above, prophylactic prescription of antibiotics for women undergoing surgical abortion has been found to reduce the risk of post-abortion infection (Sawaya et al. 1996) and should be provided where possible. 2.5.2.5 Uterine perforation Usually, uterine perforation goes undetected and resolves without the need for intervention. A study of more than 700 women undergoing concurrent first-trimester abortion and laparoscopic sterilization found that 12 out of the 14 uterine perforations were so small that they would not have been recognized had laparoscopy not been performed (Kaali et al. 1989). Where uterine perforation is suspected, observation and antibiotics may be all that is necessary. Where available, laparoscopy is the investigative method of choice. If the laparoscopy examination and/or the status of the patient gives rise to any suspicion of damage to bowel, blood vessels or other structures, a laparotomy to repair damaged tissues may be needed.

2.5.2.6 Anaesthesia-related complications Local anaesthesia is safer than general anaesthesia, both for vacuum aspiration in the first trimester and for dilatation and evacuation in the second trimester (Osborn et al. 1990, MacKay et al. 1985). Where general anaesthesia is used, staff must be skilled in stabilization management of convulsions and impairment of cardiorespiratory function. Narcotic reversal agents should always be readily available. 2.5.2.7 Long-term sequelae The vast majority of women who have a properly performed induced abortion will not suffer any long-term effects on their general or reproductive health. The exceptions are a proportion of the small number of women who have severe complications of abortion (World Health Organization 1997). Research shows no association between safely induced first-trimester abortion and adverse outcomes of subsequent pregnancies (Hogue et al. 1999). Sound epidemiological data show no increased risk of breast cancer for women undergoing first-trimester abortion (Melbye et al. 1997). According to a comprehensive review (Dagg 1991), adverse psychological sequelae occur in a very small number of women and appear to be the continuation of pre-existing conditions.

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3

3.1

Follow-up

RECOVERY PERIOD

3.1.1 Surgical methods of abortion During the observation period following abortion performed by surgical means, staff should offer women comfort and support and monitor their recovery. Health workers should take special note of women's reports of pain, since pain may be due to uterine perforation or acute haematometra ­ blood filling the uterus ­ which can be treated by inducing uterine contractions with ergometric drugs. Thus, particularly with late abortions, it is important to confirm the size of the uterus through the abdominal wall bimanually. In the absence of complications, most women can leave the health care facility as soon as they feel able and their vital signs are normal. After abortions performed later in pregnancy and after heavy sedation or general anaesthesia, recovery periods may be longer and women may require closer observation. Ideally, women undergoing surgical abortion should have a follow-up visit with a trained practitioner 7-10 days after the procedure, to assess general health.

3.1.2 Medical methods of abortion As described earlier, treatment protocols for medical methods of abortion used up to 9 completed weeks of pregnancy generally require women to remain under clinical observation for 4-6 hours after taking the prostaglandin. Providers should inspect all sanitary pads and bed pans used during the period of observation, maximizing the opportunity to confirm an abortion during this time. Women for whom complete abortion is not confirmed at that time, those who take the prostaglandin at home or those who leave the facility shortly after prostaglandin administration should be scheduled for a return visit in 10-15 days to confirm that the abortion has been completed, that there is no infection, and that no other complications have occurred. In most cases, complete abortion will be confirmed at this visit. If not, women may opt to undergo vacuum aspiration, but it is not clinically necessary for them to do so unless the physical examination, the clinical symptoms or a laboratory test suggest that the pregnancy is still growing. In view of the greater risk of haemorrhage and of incomplete abortion associated with procedures undertaken after 12 completed weeks of pregnancy, all women in these cases should remain under observation until both fetus and placenta have been expelled.

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3.2

CONTRACEPTIVE METHOD PROVISION AND STI COUNSELLING

Staff should ensure that women receive information and counselling on post-abortion contraception, including emergency contraception, before they leave the health care facility. All methods of contraception, including intrauterine devices and hormonal contraceptives, can be considered for use after abortion, as long as attention is paid to each woman's health profile and the limitations associated with certain methods (see Annex 4). The diaphragm and cervical cap should not be used until about 6 weeks after a second-trimester abortion and there is a higher risk of expulsion of intrauterine devices if inserted at the time of a second-trimester abortion (Stanwood et al. 2001). Some natural family planning methods should only be started three cycles after an abortion (World Health Organization 2000b). Special attention should be given in cases where women request sterilization to ensure their choice is not influenced by the crisis nature of the moment and to avoid later regret. Abortion service delivery sites should be able to provide most methods in the facility if the woman chooses a method. If the contraceptive chosen by the woman cannot be provided (e.g. sterilization is rarely offered at primary care level), the woman

should be given information about where and how she can get it and offered an interim method. All women should be informed about emergency contraception and consideration should be given to providing it to women who choose not to start using a routine contraceptive method immediately. Providers should discuss prevention of STIs including HIV and the importance of condom use with all women regardless of the contraceptive method chosen. Information about infection prevention should be particularly emphasized for people who may be at increased risk, and in areas of known high prevalence of HIV. Voluntary testing and counselling may be offered, or referral to HIV counselling and testing in other facilities. Dual protection, or the use of methods to protect against both pregnancy and STIs, should be promoted. 3.3 INSTRUCTIONS FOR CARE AFTER ABORTION

Women undergoing abortion should receive clear, simple, oral and written instructions about how to care for themselves after leaving the health care facility, including how to recognize complications that require medical attention. While they wait for a medically induced abortion to be completed, women should be able to contact a physician or other health worker who can answer questions and provide support.

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3

Follow-up continued

References

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After a surgical abortion, women may experience light menstrual-like bleeding or spotting for several weeks. Women should be informed that bleeding similar to or heavier than a heavy menstrual period might be expected with medical methods of abortion. Symptoms that warrant clinical attention include excessive bleeding, fever lasting more than one day and pelvic pain. Nausea, sometimes accompanied by vomiting, generally subsides within 24 hours after abortion performed by surgical methods. Staff should advise women to expect cramping, which they can usually alleviate sufficiently with non-prescription analgesics. Information on recognizing complications and how to seek help for them should be made available in pictorial form for women who cannot read. After first-trimester abortion, most women can return to their usual activities and responsibilities within hours or days. The follow-up visit is an opportunity for providers to talk with women about their experiences, if needed. For instance, women having an abortion for medical reasons or following rape may need to speak about their sense of loss or ambivalence, or may want additional counselling.

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Costa SH and Vessy MP. (1993) Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet 341:1258-1261. Creinin MD. (2000) Randomized comparison of efficacy, acceptability and cost of medical versus surgical abortion. Contraception 62:117-124. Creinin MD and Aubény E. (1999) Medical abortion in early pregnancy. In Paul M, Lichtenberg ES, Borgatta L, Grimes D and Stubblefield PG (eds). A clinician's guide to medical and surgical abortion. New York, Churchill Livingstone, pp. 91-106. Dagg PKB. (1991) The psychological sequelae of therapeutic abortion ­ denied and completed. American Journal of Psychiatry 148:578-585. Dahl V, Fjellanger F and Raeder JC. (2000) No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia. European Journal of Pain 4:211-215. Dickinson JE, Godfrey M and Evans SF. (1998) Efficacy of intravaginal misoprostol in second-trimester pregnancy termination: a randomized controlled trial. Journal of Maternal-Fetal Medicine 7:115-119. Diniz EM, Corradini HB, Ramos JL and Brock R. (1978) Efietos sobre o concepto do metotrexato (ametopterina) administrado à mãe. Apresentação de caso. Revista do Hospital das Clinicas; Faculdade de Medicine a Universidade de Sao Paulo 33:286-290. Donati S, Medda E, Proietti S, Rizzo L, Spinelli A, Subrizi D and Grandolfo ME. (1996) Reducing pain of first trimester abortion under local anaesthesia. European Journal of Obstetrics & Gynecology and Reproductive Biology 70:145-149.

El-Refaey H and Templeton A. (1995) Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. Human Reproduction 10:475-478. El-Refaey H, Rajasekar D, Abdalla M, Calder L and Templeton A. (1995) Induction of abortion with mifepristone (RU486) and oral or vaginal misoprostol. New England Journal of Medicine 382:983-987. Elul B, Ellertson C, Winikoff B and Coyaji K. (1999) Side effects of mifepristone-misoprostol abortion versus surgical abortion. Data from a trial in China, Cuba and India. Contraception 59:107-114. Elul B, Hajri S, Ngoc NN, Ellertson C, Slama CB, Pearlman E and Winikoff B. (2001) Can women in less-developed countries use a simplified medical abortion regimen? Lancet 357:1402-1405. Feldkamp M and Carey JC. (1993) Clinical teratology counseling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy. Teratology 47:533-539. Finn R, Clarke CA, Donohoe WTA, McConnell RB, Sheppard PM, Lehane D and Kulke W. (1961) Experimental studies on the prevention of Rh haemolytic disease. British Medical Journal 1:1486-1490. Fonseca W, Alencar AJ, Mota FS and Coelho HL. (1991) Misoprostol and congenital malformations. Lancet 338:56. Gemzell-Danielsson K and Ostlund E. (2000) Termination of second trimester pregnancy with mifepristone and gemeprost. The clinical experience of 197 consecutive cases. Acta Obstetricia et Gynecologica Scandinavica 79:702-706.

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References continued

Gonzalez CH, Marques-Dias MJ, Kim CA, Sugayama SM, Da Pa JA, Huson SM and Holmes LB. (1998) Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet 351:1624-1627. Greenslade FC, Benson J, Winkler J, Henderson V, Wolf M and Leonard A. (1993) Summary of clinical and programmatic experience with manual vacuum aspiration. IPAS Advances in Abortion Care 3(2):1-4. Grimes DA and Cates W Jr. (1979) Complications from legallyinduced abortion: a review. Obstetrical and Gynecological Survey 34:177-191. Grimes DA, Hulka JF and McCutchen ME. (1980) Midtrimester abortion by dilatation and evacuation versus intra-amniotic instillation of prostaglanding F2 alpha: a randomized clinical trial. American Journal of Obstetrics and Gynecology 137:785-790. Grimes D, Schulz KF, Cates W and Tyler CW. (1977) The Joint Program for the Study of Abortion/CDC ­ a preliminary report. In Hern W and Andrikopolous B (eds). Abortion in the seventies. New York, National Abortion Federation, pp. 41-46. Grimes DA, Schulz KF and Cates W Jr. (1984) Prevention of uterine perforation during currettage abortion. JAMA 251:2108-2112. Hakim-Elahi E, Tovell HM and Burnhill MS. (1990) Complications of first trimester abortion: a report of 170,000 cases. Obstetrics & Gynecology 76:129-135. Hein A, Jakobsson J and Ryberg G. (1999) Paracetamol 1 g given rectally at the end of minor gynaecological surgery is not efficacious in reducing postoperative pain. Acta Anaesthesiologia Scandinavica 43:245-247.

Henshaw RC and Templeton AA. (1991) Pre-operative cervical preparation before first trimester vacuum aspiration: a randomized controlled comparison between gemeprost and mifepristone (RU 486). British Journal of Obstetrics and Gynaecology 98:1025-1030. Ho PC, Chan YF and Lau W. (1996) Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial. Contraception 53:281-283. Hogue CJ, Boardman LA, Stotland NL and Peipert JF. (1999) Answering questions about long-term outcomes. In Paul M, Lichtenberg ES, Borgatta L, Grimes D and Stubblefield PG (eds). A clinician's guide to medical and surgical abortion. Philadelphia, Churchill Livingstone, pp 217-228. Kaali SG, Szigetvari IA and Bartfai GS. (1989) The frequency and management of uterine perforations during first-trimester abortions. American Journal of Obstetrics and Gynecology 161:406-408. Lawson HW, Frye A, Atrash HK, Smith JC, Shulman HB and Ramick M. (1994) Abortion mortality, United States, 1972 through 1987. American Journal of Obstetrics and Gynecology 171:1365-1372. Lean TH, Vengadasalam D, Pachauri S and Miller ER. (1976) A comparison of D&C and vacuum aspiration for performing first trimester abortion. International Journal of Gynecology & Obstetrics 14:481-486. MacKay HT, Schulz KF and Grimes DA. (1985) Safety of local versus general anaesthesia for second trimester dilatation and evacuation abortion. Obstetrics and Gynecology 66:661-665. Matambo J, Moodley J and Chigumadzi P. (1999) Analgesia for termination of pregnancy. South African Medical Journal 89:816.

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McKinley C, Thong KJ and Baird DT. (1993) The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol. Human Reproduction 8:1502-1505. Melbye M, Wohlfahrt J, Olsen JH, Frisch M, Westergaard T, Helweg-Larsen K and Andersen PK. (1997) Induced abortion and the risk of breast cancer. New England Journal of Medicine 336:81-85. Ngai SW, Chan YM, Tang OS and Ho PC. (1999) The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial. Human Reproduction 8:2139-2142. Ngai SW, Tang OS and Ho PC. (2000) Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Human Reproduction 15:2205-2208. Ngoc NN, Winikoff B, Clark S, Ellertson C, Am KN, Hieu DT and Elul B. (1999) Safety, efficacy and acceptability of mifepristone-misoprostol medical abortion in Vietnam. International Family Planning Perspectives 25:10-14 & 33. Orioli IM and Castilla EE. (2000) Epidemiological assessment of misoprostol teratogenicity. British Journal of Obstetrics and Gynaecology 107:519-523. Osborn JF, Arisi E, Spinelli A and Stazi MA. (1990) General anaesthesia, a risk factor for complication following induced abortion? European Journal of Epidemiology 6:416-422. Penney GC, Thomson M, Norman J, McKenzie H, Vale L, Smith R and Imrie M. (1998) A randomised comparison of strategies for reducing infective complications of induced abortion. British Journal of Obstetrics and Gynaecology 105:599-604.

Peyron R, Aubény E, Targosz V, Silvestre L, Renault M, Elkik F, Leclerc P, Ulmann A and Baulieu EE. (1993) Early termination of pregnancy with mifepristone (RU486) and the orally active prostaglandin misoprostol. New England Journal of Medicine 21:1509-1513. Powell HR and Ekert H. (1971) Methotrexate-induced congenital malformations. Medical Journal of Australia 2:1076-1077. RCOG ­ Royal College of Obstetricians and Gynaecologists. (2000) The care of women requesting induced abortion. Evidence-based guideline No.7. London, RCOG Press. Sawaya GF, Grady D, Kerlikowske K and Grimes DA. (1996) Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstetrics and Gynecology 87:884-890. Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ and Popperna S. (1999) Low-dose mifepristone 200mg and vaginal misoprostol for abortion. Contraception 59:1-6. Schaff EA, Stadalius LS, Eisinger SH and Franks P. (1997) Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. Journal of Family Practice 44:353-360. Schonhofer PS. (1991) Brazil: misuse of misoprostol as an abortifacient may induce malformations. Lancet 337:1534-1535. Schulz KF, Grimes DA and Cates W Jr. (1983) Measures to prevent cervical injury during suction curettage abortion. Lancet 1:1182-1184. Singh K, Fong YF, Prasad RNV and Dong F. (1998) Randomized trial to determine optimal dose of vaginal misoprostol for preabortion cervical priming. Obstetrics and Gynecology 92:795-798.

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References continued

Smith GM, Stubblefield PG, Chirchirillo L and McCarthy MJ. (1979) Pain of first trimester abortion: its quantification and relations with other variables. American Journal of Obstetrics and Gynecology 133:489-498. Solo J. (2000) Easing the pain: pain management in the treatment of incomplete abortion. Reproductive Health Matters 8:45-51. Sopwith W, Garner P, Hart A. (2001) Preventing infection from reusable medical equipment: a systematic review of decontamination procedures. Liverpool School of Tropical Medicine. Available online at: www.liv.ac.uk/lstm/deconreview.html. Spitz IM, Bardin CW, Benton L and Robbins A. (1998) Early pregnancy termination with mifepristone and misoprostol in the United States. New England Journal of Medicine 338:1241-1247. Stanwood NL, Grimes DA and Schulz KF. (2001) Insertion of an intrauterine contraceptive device after induced or spontaneous abortion: a review of the evidence. British Journal of Obstetrics and Gynaecology 108:1168-1173. Suprapto K and Reed S. (1984) Naproxen sodium for pain relief in first-trimester abortion. American Journal of Obstetrics and Gynecology 150:1000-1001. Swahn ML and Bygdeman M. (1988) The effect of the antiprogestin RU486 on uterine contractility and sensitivity to prostaglandin and oxytocin. British Journal of Obstetrics and Gynaecology 95:126-134. Tang OS, Thong KJ and Baird DT. (2001) Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases. Contraception 64:29-32.

Thong KJ, Robertson AJ and Baird DT. (1992) A retrospective study of 932 second trimester terminations using gemeprost (16, 16 dimethyl-trans delta 2 PGE1 methyl ester). Prostaglandins 44:65-74. Thonneau P, Fougeyrollas B, Ducot B, Boubilley D, Dif J, Lalande M and Soulat C. (1998) Complications of abortion performed under local anesthesia. European Journal of Obstetrics & Gynaecology and Reproductive Biology 81:59-63. Trussell J and Ellertson C. (1999) Estimating the efficacy of medical abortion. Contraception 60:119-135. UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction. (1997) Methotrexate for the termination of early pregnancy: a toxicology review. Reproductive Health Matters 9: 162-166. Urquhart DR and Templeton AA. (1990) Reduced risk of isoimmunisation in medical abortion. Lancet 335:914. Urquhart DR, Templeton AA, Shinewi F, Chapman M, Hawkins K, McGarry J, Rodger M, Baird DT et al. (1997) The efficacy and tolerance of mifepristone and prostaglandin in termination of pregnancy of less than 63 days gestation; UK multicentre study ­ final results. Contraception 55:1-5. Westfall JM, O'Brien-Gonzales A and Barley G. (1998) Update on early medical and surgical abortion. Journal of Women's Health 7:991-995. Winikoff B, Sivin I, Coyaji KJ, Cabezas E, Xiao B, Gu S, Du MK, Krishna UR, Eschen A and Ellertson C. (1997) Safety, efficacy, and acceptability of medical abortion in China, Cuba and India: a comparative trial of mifepristone-misoprostol versus surgical abortion. American Journal of Obstetrics and Gynecology 176:431-437.

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Wong KS, Ngai CSW, Khan KS, Tang LC and Ho PC. (1996) Termination of second trimester pregnancy with gemeprost and misoprostol: a randomized double-blind placebo-controlled trial. Contraception 54:23-25. World Health Organization. (1994) Clinical management of abortion complications: a practical guide. Geneva, World Health Organization. (WHO/FHE/MSM/94.1) World Health Organization. (1997) Medical methods for termination of pregnancy. WHO Technical Report Series 871. Geneva, World Health Organization. World Health Organization. (1999) HIV and pregnancy: a review. Geneva, World Health Organization. (WHO/CHS/RHR/99.15) World Health Organization. (2000a) Managing the complications of pregnancy and childbirth: a guide for midwives and doctors. Geneva, World Health Organization. (WHO/RHR/00.7) World Health Organization. (2000b) Improving access to quality care in family planning: medical eligibility criteria for contraceptive methods. Second edition. Geneva, World Health Organization. (WHO/RHR/00.02) World Health Organization. (2001) Fact Sheet 11: HIV and the workplace and universal precautions. Geneva, World Health Organization. Available online at: www.who.int/HIV_AIDS/nursemidwives/fact-sheet-11. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation. (1993) Termination of pregnancy with reduced doses of mifepristone. British Medical Journal 307:532-537.

World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation. (1994) Cervical ripening with mifepristone (RU 486) in late first trimester abortion. Contraception 50:461-475. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation. (2000) Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial. British Journal of Obstetrics and Gynaecology 107:524-530.

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Chapter 3 ­ Putting services in place Safe Abortion: Technical and Policy Guidance for Health Systems

Chapter 3 Putting services in place

Chapter 3 ­ Putting services in place

53

Safe Abortion: Technical and Policy Guidance for Health Systems

Chapter 3 Summary

Planning and managing abortion services requires consideration of a number of factors which are applicable irrespective of the circumstances under which abortion is legal, or who has responsibility for decision-making and/or implementation within the health system. They apply whether services are public, private or non-governmental. In most cases, minor adaptations of existing facilities, acquisition of minimal additional equipment, or provision of basic training can allow for services to be provided where none previously existed or can improve the quality, safety, efficiency, and capacity, of existing services. These adaptations should be based on careful planning that encompasses the following: Assessment of the current situation. This need not be long or complex. Items to review in such an assessment are: laws and regulations governing availability of and access to safe abortion care; the extent and level of services currently available; the quality of services as currently provided, including the procedures being used for inducing abortion and dealing with complications of unsafe abortion; characteristics of users; and the attitudes and knowledge of health care providers. Establishment of national norms and standards governing the provision of quality abortion care. These norms and standards should cover: types of abortion services and where they can be provided; essential equipment, supplies, medications and facility capabilities; referral mechanisms; respect for women's informed decision-making, autonomy, confidentiality and privacy, with attention to the special needs of adolescents; and special provisions for women who have suffered rape. Definition of provider skills, training, supervision and certification processes. In particular, it must be clear which types of health care providers can provide abortion. Other details to be elaborated include the essential content for curricula on abortion services, supervision standards, and certification and licensing requirements to ensure that providers and institutions meet essential criteria for provision of safe abortion. Monitoring and evaluation of services. This includes the collection of routine service statistics and patient information, the use of supervisor checklists, and periodic special studies. Financing. Health service budgets should include costs of staff, training programmes, instruments, supplies and medications, and capital costs. Consideration also needs to be given to making services affordable to women who need them. Costs of adding safe abortion services to existing health services are likely to be modest, relative to the gains for women's health.

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Chapter 3 ­ Putting services in place Safe Abortion: Technical and Policy Guidance for Health Systems

1

Assessing the current situation

Assessment will help identify where services need to be established and/or how existing services need to be improved. Basic assessment at national, regional and local levels need not be long or complex. In most cases, a review of existing information, consultation with all relevant "stakeholders" (including Ministry of Health officials, service providers, women, relevant representatives of civil society, and technical/donor agencies) and observations of service delivery at various levels of the health service, will provide the necessary information. References giving details of such approaches (rapid assessment techniques and situation analyses) are listed in Annex 1. One methodology which has been used effectively in a variety of countries is the Strategic Approach to Improving the Quality of Care of Reproductive Health Services (World Health Organization 1999, World Health Organization 2002a). The Strategic Approach relies on the creation of an assessment team representing a broad range of stakeholders who conduct a field-based assessment of the available technologies, the quality of services being provided and women's needs and perspectives. Whatever assessment approach is used, it is important to ensure that multiple perspectives are incorporated. This helps to ensure that recommendations and plans

based on the assessment will be broadly acceptable and therefore more likely to be implemented. It is particularly important to include users' and potential users' perspectives on services as they are the main source of identifying barriers to service use. It is also important that the assessment examine people's access to reproductive health services generally, and specifically their access to contraceptive information and services, since these have an impact on the incidence of unintended pregnancy. When the assessment includes direct observation of women and providers, it is essential to obtain prior informed consent from both. Examples of questions to answer through an assessment are listed below. The typical data sources for answering these questions will be health service records (both local and national), reports to the Ministry of Health, local or national social science studies on providers' and/or users' perspectives and, to some limited extent, the Demographic and Health Surveys (DHS) and other national health surveys. Much may be gleaned from reviewing existing literature, but in most cases such review will need to be supplemented with information from a rapid assessment. With all these sources, it is important to note that under-reporting about abortion ­ whether legal or illegal, safe or unsafe ­ is widespread.

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1

Assessing the current situation continued

a) What are the laws, policies and regulations, including clinic policies, governing availability of, and access to, safe abortion care? Health professionals and the public may assume that the law is much more restrictive than it is, and thus services may not be available or women may not have the access to which they are entitled by law. Alternatively, health professionals may be aware of the law, but do not put it into practice for a variety of reasons. Close examination by both legal and public health experts of the text of the law and how the law is enacted in practice is an important step in an assessment. For example, where laws and policies require third party authorization or certification, such as hospital abortion committees, spousal authorization or medical or police certification of forceful intercourse, the rapid assessment will probably reveal excessive delays, causing harm to women's health. The assessment may suggest opportunities or approaches to streamline procedures and/or inform the public, lawyers, judges and doctors more clearly about when women are eligible for services and how they can access them. Effecting such change may take time, but this has been done successfully in some countries (Veira Villela and de Oliveira Araujo 2000, Billings et al. 2002).

b) What is the incidence of legal abortion and of the complications of unsafe abortion? Who is using the current services, and who is not obtaining access? Estimating the incidence of unsafe abortion, and the numbers of legal abortions currently carried out may be difficult, especially in situations where access to legal abortion is restricted. In almost all situations, however, social science studies often furnish data which can help to establish a general picture of the situation (Mundigo and Indriso 1999). Health service statistics can provide estimates of legal abortions and numbers of hospital admissions for complications of unsafe abortion. Survey data, for instance from DHS, may exist on the extent of unwanted or ill-timed pregnancy. Where available, data on the age, marital and socio-economic status of women using legal abortion services and women suffering complications from unsafe abortions will give an indication of which women are currently using services. These data can then be used to tailor programme design. For example, if information about women treated for the complications of unsafe abortion reveals that they are in the under-25 age group, policy-makers and programme planners will need to develop strategies to provide young people with information and education about sexual and reproductive health,

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and about availability of contraceptive and abortion services. Additional information about health providers' attitudes may suggest further training for them to be open and non-judgemental with adolescents and young people. c) Where are legal abortion services currently carried out? Are they available at primary health care level, secondary level or only at tertiary care level? Are these public, private or non-governmental facilities? Are they provided in all parts of the country? Are they freestanding or integrated with other health services? What proportion of abortion services is provided in each of these kinds of facilities? The assessment may indicate that services are primarily available only in urban hospitals. In this case, the initial priority might be to train and equip staff in lower-level facilities including those in rural areas, at least to provide first-trimester procedures and effective referral for more complicated cases. d) What is the current quality of care in abortion service delivery? What procedures are used for inducing abortion, and for dealing with the complications of unsafe abortion, at different durations of pregnancy? What is the technical quality of these services? Is appropriate information provided to women? Do women receive

pre- and post-abortion contraceptive counselling and services? Does the quality of care vary at different levels of service delivery or in different regions of the country? Some of this information may be available from health service records. A review of service protocols will indicate whether, as a matter of policy, quality of care standards are clear and whether women are to be given contraceptive information and services after abortion. Rapid assessment would determine whether practices meet the standards. Direct observation of services during the assessment may reveal poor quality of care such as lack of necessary supplies, failure to ensure privacy, or poor technical skills of providers. Such shortcomings can be addressed by investment in logistics systems, or improved training and supervision, for example. e) What are the attitudes and knowledge of health care providers concerning abortion? How knowledgeable are they about both the law and clinical techniques and about where services can be obtained? How well do their responses match practices identified by the team during rapid assessment? Existing information on these aspects is quite limited in most countries, but gathering it is important because health care providers' attitudes and practices are important determinants of women's access to safe, legal services.

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For instance, the assessment may reveal that some providers, or potential providers, feel ambivalent or negative about abortion, even where it is legal on request (Dickson-Tetteh et al. 2000). In this case, programme planners will need to consider ways to ensure that eligible women can access services.

refresher training for providers to update their technical and inter-personal communication skills. g) What is the cost to the health system of providing safe abortion? What are the costs of treating the complications of unsafe abortion? Information on direct costs may be available through health service records, or obtained through a rapid survey of health services, both public and private. More comprehensive information on costs can be obtained through more in-depth studies. Estimates for one year at one institution are adequate for the purpose of initial assessment (King et al. 1998). Information can also be analysed by applying costing spreadsheet tools (see Annex 1). This information will help guide rational decisionmaking about what services can be provided at what level of the health system, and what methods could be introduced at each level.

f) What are women's knowledge about and perspectives on abortion and abortion services? Women's knowledge and perceptions about services and the social context may also represent a barrier to using the services to which they are entitled. Studies show that women often fear mistreatment, negative attitudes of husbands or partners, or social condemnation (Mundigo and Indriso 1999), all of which inhibit their seeking care. An assessment should also determine whether women know about their rights with regard to abortion, and how much it costs to obtain an abortion in both the public and private sectors. For example, if the rapid assessment reveals that women dislike public services and do not use them for a variety of reasons such as lack of confidentiality/privacy, fear of criticism, or perceived poor quality of care, programme planners and managers will need to take measures to improve the quality of care. This could be addressed through

2

Establishing national norms and standards

In many countries, written norms and standards for abortion service delivery do not exist, and in these situations they need to be established. Where they already exist, they should be reviewed regularly to ensure standards reflect new evidence of best practice. Norms and standards should be framed to ensure that good-quality abortion services are available to the extent

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permitted by law. They should set criteria for providing the essential elements of good-quality abortion care delivered by public, private and non-governmental agencies, including: Types of abortion services and where they can be provided; Essential equipment, supplies, medications and facility capabilities; Referral mechanisms; Respect for women's informed decision-making, autonomy, confidentiality and privacy, with attention to the special needs of adolescents; Special provisions for women who have suffered rape. 2.1 TYPES OF ABORTION SERVICES AND WHERE THEY CAN BE PROVIDED

In all situations, a well-functioning referral system is essential (see section 2.3). Higher-level facilities, with appropriate investments in training and equipment, can be used to train health workers from lower-level facilities, thereby extending the geographic reach through the health system. In cases where services are widespread but of poor quality, the first steps will be to assess the main reasons for the shortcomings, and develop and implement recommendations. This may include retraining staff, or improving infrastructure and equipment at all levels of the system. In most cases, integration of abortion services into existing reproductive health services is likely to be the easiest and most cost-effective strategy. 2.1.1 Community level Community-based health workers play an important role in helping women avoid unwanted pregnancy through providing information and contraceptives, and informing them about the consequences of unsafe abortion. They also need to be able to inform women how to obtain safe, legal abortion care without undue delay, and refer women with complications of unsafe abortion for appropriate care. 2.1.2 Primary-care facility level Primary health-care centres generally have basic medical capacity and some trained health care workers. Both vacuum aspiration and medical methods of abortion can be considered at this level, since they do not require overnight stay.

Establishing early abortion services at the primary level can greatly improve access for eligible women. Training and equipping health professionals at the primary level to provide early abortion services and to make appropriate referrals may thus be one of the most important investments to consider. Where capacity to provide quality reproductive health services at the primary level does not yet exist, a minimum step is to create effective referral mechanisms from primary to higher levels.

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Establishing national norms and standards continued

Staff are likely to include nurses, midwives, health assistants, and, in some contexts, physicians. Health personnel who have already been trained and have demonstrated ability to perform a bimanual pelvic examination to diagnose signs of pregnancy and to perform a transcervical procedure such as IUD insertion, can be trained to perform vacuum aspiration (Freedman et al. 1986, Greenslade et al. 1993). Where medical methods of abortion are registered and available, such staff can also administer and supervise the treatment (Coyaji 2000). As with management of normal birth and of spontaneous abortion, referral arrangements must be in place to ensure prompt, higher level of care, if required. For this reason, trained staff should be available on call during and after health centre hours, in case of need. 2.1.3 District hospital (first referral) level District hospital level facilities should offer all primary-care level abortion services as outlined in Table 3.1, even where such services are also available at lower levels of care. Specialized elements of care are rarely required for abortion and should not be a routine part of abortion service delivery, especially where resources are limited.

For example, routine use of specialized equipment such as ultrasound for early abortion increases costs to the health system and is not necessary for the provision of early abortion (RCOG 2000). General anaesthesia should not normally be used for early abortion since it increases the risks and costs of the procedure (Lawson et al. 1994). Hospitals should therefore offer abortion care on an outpatient basis, which is safe, minimizes costs and enhances convenience to the woman. Referral hospitals that are staffed and equipped to provide emergency obstetric care are capable of managing the complications of abortion. They should therefore be prepared to accept abortion-related referrals from health care facilities throughout the catchment area. 2.1.4 Secondary and tertiary referral hospitals Secondary and tertiary hospitals should have staff and facility capacity to perform abortions in all circumstances permitted by law and to manage all complications of unsafe abortion. The provision of abortion care at teaching hospitals is particularly important to ensure that relevant cadres of health professionals develop competence in abortion service delivery during clinical training rotations.

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Table 3.1 Types of services suitable to each level of the health care system Community level Public health education/information on reproductive health, including family planning and abortion Community-based distribution of appropriate methods of contraception, including emergency contraception All health workers trained to provide information on, and referral to, legal abortion services All health workers trained to recognize abortion complications and promptly refer women for treatment Transportation to services for abortion and for management of complications of unsafe abortion All health workers (and other key community professionals such as police or teachers) trained to recognize signs that girls or women have been subjected to rape or incest and to provide referral to health or other social services Primary-care facility level All elements of care mentioned for the community level All health care workers providing reproductive health services trained to provide counselling on family planning, unwanted pregnancy and abortion A broader range of contraceptive methods (including, e.g., IUDs and injectables) Vacuum aspiration up to 12 completed weeks of pregnancy (see Chapter 2) Medical methods of abortion up to 9 completed weeks of pregnancy (see Chapter 2) Clinical stabilization of, and provision of antibiotics to, women with complications of unsafe abortion Vacuum aspiration for incomplete abortion Prompt referral and transport for women needing services for abortion or for management of abortion complications that cannot be provided on site District hospital level All elements of abortion care mentioned for the primary-care level Provision of sterilization in addition to other contraceptive methods Abortion services for all circumstances and stages of pregnancy in which it is permitted by law Management of abortion complications Information and outreach programmes covering the full catchment area Training of all relevant cadres of health professionals (pre-service and in-service) in abortion service provision Referral hospitals (secondary and tertiary) All elements of abortion care mentioned for the previous levels Management of all abortion complications, including those that cannot be managed at district level

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2.2

Establishing national norms and standards continued

ESSENTIAL EQUIPMENT, SUPPLIES, MEDICATIONS AND FACILITY CAPABILITIES

The following table (Table 3.2) gives a summary of what is needed for providing abortion services at different levels of the health care system. Most of the supplies, equipment and infrastructure needed for vacuum aspiration and medical methods of abortion are the same as those needed for gynaecological care and for clinical contraception. A detailed list of essential equipment and supplies for the provision of manual vacuum aspiration is included in Annex 3. Details about the drugs needed for the management of complications, such as oxytocin, IV fluids and antibiotics, can be found elsewhere (World Health Organization 2000). These instruments and medications should be routinely included in the planning, budgeting, procurement, distribution and management systems. Criteria for determining what instruments to use are: quality, durability, system ability to ensure consistent availability and maintenance over time, and cost.

The introduction of vacuum aspiration can help health systems increase the availability of and accessibility to abortion since its ease of use makes it appropriate for facilities at the primary health care level. In addition, the costs are relatively low (Lean et al. 1976). Costing studies of manual vacuum aspiration have been carried out on its introduction for treating complications of unsafe abortion. These demonstrate substantial reduction in costs from the use of manual vacuum aspiration as well as improved quality of care (Anonymous 2000, Brambila et al. 1999, El Shafei et al. 1999). Programmatic and resource considerations may influence decisions about which method of vacuum aspiration to offer. In hospital settings and other sites that perform a high volume of abortions, the use of electric vacuum aspiration may be more efficient than manual vacuum aspiration. However, where electric vacuum aspiration is being used and where electrical power supply is unreliable, back-up availability of manual vacuum aspiration is essential. Vacuum aspiration has proven highly acceptable to providers in different settings (Bradley et al. 1991, Ekwempu 1990, Population Council 2000a, Population Council 2000b, University of North Carolina 2001).

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Table 3.2 Instruments, medications and facility requirements for abortion Method Vacuum aspiration Instruments and medication - Basic gynaecological and medical instruments and supplies (e.g., open speculum, ring or sponge forceps, antiseptic solution, gauze or swabs, gloves), tenaculum - Mechanical dilators (Pratt or Denniston), osmotic dilators, or misoprostol for cervical dilation - Needles and local anaesthetic for paracervical block - Analgesics - Suction: manual or electric vacuum aspirator and tubing - Cannulae: flexible or rigid, angled or straight; different sizes - Sieve and glass bowl for tissue inspection Facility requirements Instruments and medication Private area for counselling Clean treatment area offering privacy Examination table with leg supports or stirrups Bed Stool for provider Clean water Strong lighting Supplies for decontamination and cleaning and high-level disinfection of instruments Disposable waste container Adequate toilet facilities

Medical methods of abortion

Basic gynaecological and medical instruments and supplies (e.g. open speculum, gauze or swabs, menstrual pads, gloves) Depending on the protocol used:

- Mifepristone + misoprostol or gemeprost - Analgesics - Glass bowl for tissue inspection

- Private area for counselling - Private area with chairs to wait for expulsion separate from women giving birth - Adequate toilet facilities - Capacity to provide or refer for vacuum aspiration

D&E

All items listed for vacuum aspiration and: - Larger dilators and large bore cannula - Special forceps (eg. Sopher or Bierer) for later procedures - Oxytocin

All those listed for vacuum aspiration

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Pharmaceutical Products Moving in International Commerce (see Annex 1 for online information). Some countries, but not all, also have registration requirements for medical devices. Programme managers should check whether product registration is required before importation of devices such as manual vacuum aspiration kits. The commodities included in Table 3.2 that are specific to the provision of abortion services should be included in the national medical supplies logistics management programme and be available for those health facilities that require them. 2.3 REFERRAL MECHANISMS

Instruments for manual vacuum aspiration are made for either single use or multiple use. Where instruments will be reused, it is essential to purchase those that can withstand multiple use and cleaning. Instruments for single use offer the advantage of ensuring sterility of equipment and thus of safety to the woman, as well as being convenient for the provider. The disadvantage is that supplies cost more and must be regularly available. They also need to be carefully disposed of to avoid health risks to providers and the community. Reusable equipment saves costs in terms of supplies, but rigorous cleaning and disinfection procedures must be followed (see Chapter 2, section 2.5.1). 2.2.1 Regulatory requirements for drugs and devices Each country has specific regulatory requirements for the registration and importation of drugs. However, WHO's Model List of Essential Medicines, which has been adapted by many countries as a National Essential Drugs List, includes non-narcotic analgesics such as non-steroidal anti-inflammatory agents (e.g. ibuprofen), tranquillisers (e.g. diazepam) and local anaesthetics (lidocaine) (World Health Organization 2002b). Inclusion on the National Essential Drug List usually means that the drug is registered and available in the country. Where a drug is not registered, some countries will allow importation through the WHO Certification Scheme on the Quality of

It is extremely important for the provision of safe abortion services that a well-functioning referral system be in place. All health centre, clinic or hospital staff should be able to direct women to appropriate services if they are not available on site. Referral and transport arrangements among various levels of the health care system are necessary to ensure that (a) women who need services can obtain them in a timely manner, and (b) women who need care for complications of unsafe abortion receive treatment promptly. If women presenting with an unwanted pregnancy are not eligible for a legal abortion, it is essential that health care providers are able to offer support, information and/or advice to help them make plans for the continuation of the pregnancy and referral for prenatal care.

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Key elements in a functioning referral and transport system include: standard procedures for determining when referral is necessary and how to make referrals, including arrangements for transport; standard procedures for facilities to accept and treat women who are referred and for reporting back to the referring centre; guidelines on handling patient information to ensure both safe and appropriate care, as well as confidentiality; guidelines for assessing clients' needs for referral to other types of services, such as STI or HIV services, social services or counselling, and judicial services for women who have suffered rape. 2.4 RESPECT FOR WOMEN'S INFORMED DECISION-MAKING, AUTONOMY, CONFIDENTIALITY AND PRIVACY, WITH ATTENTION TO THE SPECIAL NEEDS OF ADOLESCENTS

standards should include protection for: informed and free decision-making, autonomy in decision-making, confidentiality and privacy (Cook and Dickens 2000). These standards are reinforced by international human rights standards contained in, amongst others, the International Covenant on Economic, Social and Cultural Rights, and the Convention on the Elimination of All Forms of Discrimination Against Women. 2.4.1 Informed and free decision-making Women trying to resolve the problem of an unwanted pregnancy may often feel they are in a vulnerable position, especially vis-à-vis the health services. They need to be treated with respect and understanding. Health providers should therefore be supportive of the woman and give her information in a way that she can understand and recall, so that she can make a choice about having or not having an abortion to the extent permitted by law, free of inducement, coercion or discrimination. Health providers should also be aware of situations in which a woman may be coerced into having an abortion against her will, based, for instance, on her health status such as being infected with HIV. In such cases, the provider should endeavour to ensure fully informed and free decision-making.

National norms, standards and regulations should support both women's ability to exercise their reproductive and other rights, and health care workers' fulfilment of their ethical obligations. Within the framework of national abortion laws, norms and

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Health workers have a right to conscientious objection to providing abortion, but they have an ethical obligation to follow professional ethical codes, which usually require health professionals to refer women to skilled colleagues who are not, in principle, opposed to termination of pregnancy allowed by law. If no alternative provider is available, the health worker must provide abortion to save the woman's life or to prevent permanent damage to her health in accordance with national law. When a hospital, clinic or health centre has been designated as a public facility offering services allowed by law, it cannot endanger women's lives or health by refusing services. It should provide abortion services on the grounds allowed by the law. 2.4.2 Autonomy in decision-making (third party authorization) The fundamental ethical principle of respect for persons includes respecting their autonomy. Autonomy means that mentally competent adults do not require the consent (authorization) of any third party, such as a husband or partner, to access a health service. Therefore, health providers should not impose a requirement of spousal authorization unless required by enacted law and related regulations.

Respect for persons also includes the obligation to protect vulnerable people. Unmarried women, adolescents, those living in extreme poverty and those facing violence in the home, may be considered particularly vulnerable. Stigma and discrimination associated with physical and mental disabilities and health status such as HIV infection are widespread and may be used as a reason to coerce women into having an abortion. Health providers have an ethical obligation to ensure that such women receive necessary health services. In regard to parental consent (authorization) for minors, nearly all Governments have ratified the Convention on the Rights of the Child (CRC). Article 5 of the Convention provides that "States parties shall respect the responsibilities, rights and duties of parents...to provide, in a manner consistent with the evolving capacities of the child, appropriate direction and guidance in the exercise by the child of rights recognised in the present Convention." In addition, however, Article 3, which contains one of four guiding general principles that govern the implementation of all articles of the Convention, states that, "In all actions concerning children [defined as every human being below the age of 18 years] whether undertaken by public or private social welfare institutions, courts of law, administrative authorities or legislative bodies, the best interest of the child shall be a primary consideration."

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Special considerations for adolescents Adolescents often lack knowledge about sexuality, contraception, how pregnancy occurs, what the signs of pregnancy are, and sexually transmitted infections. Young and unmarried adolescents in particular may not admit to having had sex and thus the possibility of pregnancy. They may have limited experience in talking to adults on such matters and in accessing and using health services to address their sexual health and reproductive health needs. Adolescents need a supportive environment in which they can express their needs, fears and embarrassment without being judged or "talked down" to. Health care providers must overcome their possible discomfort with adolescent sexuality, particularly of unmarried adolescents, since it is a reality in most places. They also need knowledge and appropriate skills to handle adolescents which include special history-taking skills. For instance, they should be gentle and ask simple questions in plain language. They may need to repeat questions, and probe carefully and with consideration. They may have to suggest different responses to encourage adolescents to speak since adolescents often need time to reveal their problems. It is essential that service providers clearly guarantee confidentiality by ensuring the adolescent that they will not share the information about her visit to the health centre with anyone. "Adolescent-friendly" health services may need to be developed to ensure that adolescents have access to needed services. Frequently this can be achieved by reorienting existing services to better meet the needs of adolescents. This might involve ensuring services are open at times and places where adolescents can reach them, and ensuring that fees are affordable. The existence of such services must be made known to adolescents and their families, and community support is often helpful for this. (World Health Organization, 2002c)

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Health workers should encourage minors to consult parents or another trusted adult about their pregnancy. If the girl indicates that is not possible (e.g. a parent is abusive), service providers should not require parental consent, unless required by enacted law and related regulations. Health care providers need to be trained on how to inform, counsel and treat adolescents according to their evolving capacities to understand the treatment and care options being offered, and not according to some arbitrary age cut-off. 2.4.3 Confidentiality Providers have a duty to protect patients' information against unauthorized disclosures, and to ensure that patients who do authorize release of their confidential information to others do so freely and on the basis of clear information. The fear that confidentiality will not be maintained deters many women ­ particularly adolescents and unmarried women ­ from seeking health care services and may drive them to clandestine and dangerous providers or to self-induced abortion. Unless the woman explicitly approves a provider's consultation with her spouse or parent or anyone else not essential to ensure safe and appropriate care, such consultation constitutes a serious breach of confidentiality.

2.4.4 Privacy To the maximum extent possible, health service managers should ensure that facilities provide privacy for conversations between women and providers, as well as for actual services. Privacy can be accomplished, at a minimum, by, for example, providing a single procedure per room at any one time, putting up curtains on windows and doorways, and providing a simple cloth or paper drapes for the woman for the procedure. 2.5 SPECIAL PROVISIONS FOR WOMEN WHO HAVE SUFFERED RAPE

Women who are pregnant as a result of rape are in need of particularly sensitive treatment, and all levels of the health system should be able to offer appropriate care and support. Norms and standards for provision of abortion in such cases should be elaborated and training provided. Such standards should not impose unnecessary administrative or judicial procedures such as requiring women to press charges or to identify the rapist (Billings et al. 2002) (see also Chapter 4). The standards should ideally also be part of comprehensive norms and standards for the overall management of survivors of rape, covering physical and psychological care, emergency contraception, treatment for STIs or injuries, collecting forensic evidence, and counselling and follow-up care (World Health Organization and United Nations High Commissioner for Refugees 2002).

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3.1

Ensuring provider skills and performance

PROVIDER SKILLS AND TRAINING

Making safe, legal abortion services accessible to all eligible women is likely to require involving midlevel health professionals because trained medical doctors are not sufficiently available in many parts of the world. In a number of countries midlevel providers such as midwives and other skilled health care workers who are not physicians have been trained to deliver quality postabortion care and abortion care (Billings et al. 1999, Dickson-Tetteh et al. 2000, Population Council 2000b, University of North Carolina 2001, Yumkella and Githiori 2000). A comparative study has shown no difference in complication rates between women who had first trimester abortions with manual vacuum aspiration performed by a physician assistant and those who had the procedure performed by a physician (Freedman et al. 1986).

Health workers already competent to provide basic abortion services can be trained to provide more complex care. For example, health workers who perform abortions for pregnancies up to nine weeks' duration can be taught to perform abortions for later stages of pregnancy. Providers who perform vacuum aspiration for treatment of incomplete abortion can learn to use the technique for safe abortion with modest additional training. Skills training required for provision of safe abortion should be included into pre- and in-service curricula of health providers who are allowed to provide abortion services. Skills for the recognition and management of complications of abortion should be included in the curricula for all health care providers who treat women. All staff should also receive periodic updating in these skills.

Midlevel providers refers to a range of non-physician clinicians ­ midwives, nurse practitioners, clinical officers, physician assistants, and others ­ whose training and responsibilities differ among countries but who are trained to provide basic, clinical procedures related to reproductive health including bimanual pelvic examination to determine pregnancy and positioning of the uterus, uterine sounding, transcervical procedures, and who can be trained to provide an early abortion. [Definition proposed and agreed upon by participants at the Technical Consultation in September 2000.]

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Enable clients to make informed decisions; Conduct a safe and accurate bimanual pelvic examination to diagnose pregnancy, as well as size and position of the uterus and to reach an appropriate decision to carry out an abortion or refer to a higher level of service; Recognise or suspect ectopic pregnancy; Accurately recognize the signs and symptoms of RTIs and STIs; Recognise signs of physical abuse; Administer drugs correctly; Accurately carry out the abortion procedure(s) for which they are being trained; Take effective action in case of complications before, during or after the procedure; Make effective referrals to other appropriate services; Provide contraceptive information and services; Clean and ensure safety of all equipment used for the procedure; Make accurate records. Table 3.3 lists recommended training content for all health professionals. Details of training curricula and related resource materials are included in Annex 1.

3.1.1 Training programmes Training programmes, both pre- and in-service, should be based on a competency approach including supervised practice sufficient to allow the health practitioner to demonstrate clinical competence. Programmes should use a variety of teaching and learning methodologies and should address both technical and clinical skills as well as attitudes and beliefs of the service provider. This may require a values clarification process which allows health providers to differentiate between their own values and the rights of the client to receive quality services. Programmes must be conducted in facilities that have sufficient patient flow to allow all trainees to have the requisite practice, including practice in managing complications. Curricula may vary in content as well as length of training depending on the skills the health provider already has on entry into the training programme (see Table 3.3 for full list of essential content). All training must ensure that the health practitioner is competent to: Use a wide range of interpersonal communication skills to establish effective rapport and communication with all service users, respecting their human right to be treated with dignity and respect, and to confidentiality; Effectively transmit and discuss sensitive information regarding sexual behaviour and pregnancy;

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Table 3.3 Essential content for curricula on abortion services Background for abortion service delivery Legal, regulatory and policy provisions Health effects of unsafe abortion Counselling and provider-patient interaction Clarification of providers' attitudes and beliefs with regard to abortion Privacy and confidentiality Interpersonal communication and counselling skills Information on abortion and contraception Issues and risks associated with HIV and other STIs Groups needing special care, such as adolescents, refugees, women with HIV or STI infection Recognition of signs that the woman has been subjected to violence, and guidance in helping her obtain additional counselling and services Ethical responsibility to provide abortion National norms and standards for abortion care

Clinical skills Anatomy and physiology relevant to pregnancy and abortion Pre-procedure assessment: history, examinations, pregnancy dating, etc. STI screening Abortion techniques Infection prevention Administrative/managerial issues and quality assurance Record-keeping and reporting Conditions for maintaining privacy and confidentiality Logistics, equipment and inventory management Monitoring and evaluation Mechanisms for effective referral and transport to qualified facilities Standards for supervision Pain management Recognition and management of, and/or referral for, complications of abortion Management and care following the procedure, including contraceptive information and services Criteria for referral and how to refer cases beyond the provider's competence

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3.2

Ensuring provider skills and performance continued

SUPERVISION

ensuring providers' access to the necessary equipment, commodities, and spaces to provide counselling and services assuring privacy and confidentiality; monitoring the need for, and ensuring, in-service training of staff; monitoring and ensuring access to services without discrimination on the basis of, for instance, age or marital status, or that no unauthorized charges are made; and ensuring fully informed and free consent about abortion and post-abortion contraception. An important tool for supervision can be a checklist of items that supervisors are to monitor regularly (see Table 3.4). Such a checklist needs to be developed locally to reflect particular circumstances, and administered so as to maintain quality of care.

The service system must enable supervisors to ensure that service delivery meets norms and standards, satisfies clients' needs and respects their rights. Supervisors' duties include: creating a respectful environment by demonstrating supportive attitudes and behaviour towards providers and clients; assigning jobs and tasks to health workers with appropriate skills and monitoring their work to ensure both technical quality and compassionate care;

Table 3.4 Categories for inclusion in supervisor checklist Equipment (availability, amount, condition, cleaning, sterilization, storage) Supplies (adequate, not outdated, stored appropriately) Observation of counselling given Observation of clinical services Provisions for privacy Cleanliness of the facility Accuracy and completeness of records Review of statistical records and patient files for completeness Analysis of basic service statistics

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3.3

CERTIFICATION AND LICENSING OF HEALTH PROFESSIONALS AND FACILITIES

Where certification of abortion providers is required, its sole purpose should be to ensure that providers meet essential criteria for the safe provision of care, as with other medical procedures. Certification and licensing requirements should not be used to exclude categories of health professionals. As mentioned in section 3.1 above, many different categories of health providers can be trained to provide safe abortion. In those countries in which facilities offering abortion are licensed, the licensing requirements must meet the nationally agreed criteria. Facility licensing is to ensure client safety and comprehensiveness of care. However, such licensing requirements should not impose excessive requirements for sophisticated equipment, infrastructure or staff that are not essential to provision of safe services and would unnecessarily restrict access.

eligible by law. Over time, if baseline information has been collected, including data on mortality and morbidity from unsafe abortion, and if basic service statistics are routinely and accurately kept, programmes will be able to evaluate the extent to which full access to legal services reduces maternal mortality and morbidity. These statistics and other information gathered through monitoring and evaluation should be shared and discussed with stakeholders and used to make decisions about improvements to services. 4.1 MONITORING

4

Monitoring and evaluation of services

As with all health services, abortion services should be subject to quality monitoring and evaluation. The regular and accurate collection of service statistics and regular monitoring and evaluation at the facility level are a key to maintaining and improving the quality of services delivered. They can also help in assessing whether abortion services are actually available to those women

Monitoring oversees the processes of implementing services, including changes over time. Routine monitoring can assist managers and supervisors to identify and manage or avoid problems before they become serious or overwhelming. Good monitoring includes listening to providers who can have important recommendations to improve quality of care. Well designed monitoring enables facility managers and staff supervisors to give feedback to staff on problems and to engage staff in a participatory process to implement solutions. At the facility level, processes and mechanisms for monitoring services include case reviews, logbook review, observation, checklists, facility surveys and maternal death audits, all of which can be used to improve quality of care (see Annex 1 for further reading).

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Monitoring and evaluation of services continued

Routine monitoring should include: Analysis of patterns or problems in services using service statistics (e.g. numbers of women seen but not provided with services, numbers of complications, numbers of contraceptive methods provided by type) Proportion of women seeking repeat abortions Observation of counselling and clinical services to assess quality of interaction with the woman throughout the process, to correct any shortfalls in adherence to technical standards, or other practices that jeopardise quality of care (e.g. judgmental attitudes, imposition of "informal charges") Functioning of logistics system to ensure regular supply of equipment and consumables Regular aggregation of data from facility level upwards Assessment of progress to remedy problems identified in routine monitoring.

As far as feasible, service-delivery facilities should integrate data on abortion services into regular record systems (e.g. forms, logbooks, supply stock records, checklists, clinical client records, daily activity registers) rather than create separate ones. Basic service statistics include, at a minimum, a record of abortions provided, women seen but not provided with services, women referred to higher levels of care, treatment of complications of abortion and contraceptive methods accepted. The amount and types of service statistics required to be recorded should be suited to the ability and workloads of staff. It is more valuable to have a narrow range of accurate data with a good feedback mechanism than to impose reporting requirements that staff are unable or unwilling to meet. Selected facility-level data should be sent routinely to higher levels to enable monitoring across facilities and geographic areas, and should be used at the national level for informing policy and planning. It can also be very useful to monitor the costs to the health facility of providing legal abortion and of treating complications of unsafe abortion.

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Table 3.5 Suggested data sources and indicators for monitoring and evaluating abortion services Routine service statistics Numbers of abortions provided, by completed week of pregnancy and by type of procedure Time between first consultation and abortion Number of women referred elsewhere, by reason Number of women seen but not provided with services, by reason Number of women treated for complications, by type of abortion procedure Contraceptives provided, by type Referrals for contraception Periodic evaluation Percentage of service delivery points offering abortion care, and their distribution by geographic area and level of the health care system, and patterns of utilization Number of providers performing abortion and their distribution by geographic area and level of the health system Number of health workers trained, by type; assessment of quality of training Assessment of quality of care provided Costs of abortion services and of treating the complications of abortion, by type of procedure and type of provider, and any fees charged Periodic special studies (client satisfaction, proximity of women to facilities, costs, impact, etc.) Number of staff needing in-service training and numbers trained Patient information (kept in patient file) Age, parity, marital status Reason(s) for referral Reason(s) for refusal Follow-up care given Contraceptive method chosen Fee charged, if any

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Monitoring and evaluation of services continued

EVALUATION

4.2

Evaluation assesses the relevance, effectiveness, efficiency, sustainability and impact of services using service statistics from monitoring, as well as special investigations to assess the extent to which programme goals are being accomplished. For example, has quality improved? Are all eligible women gaining access? Are quantitative and qualitative training objectives being met? Has the number of service delivery points increased? Evaluations can be conducted at health centre level, regional or sub-regional and national levels and should be designed early in programme development to include both a baseline assessment and scheduled evaluation points. Periodic, client-based evaluations to assess women's experiences, complications, quality of care received, and access to services will provide important information for improving clinic and outreach services. This can be done with questionnaires, observation guides, and exit interviews. Similar evaluations should also be carried out with providers, to assess their attitudes, knowledge, practices, needs and ideas for improving services. Impact evaluations can measure the extent to which improved access to and quality of services for eligible women help to meet health goals. For example,

periodic special studies of a sample of facilities and catchment areas can assess increases in the use of legal services. Special studies could also examine changes in hospital admissions for complications of unsafe abortion before and after improvements are made. Like other evaluations, assessment of impact requires a strong baseline assessment and clear specification of programme objectives and indicators. In most instances, it is more important to define a few clearly measurable indicators than to attempt to collect a comprehensive list of data, especially where health system research capacity is limited. Where capacity is strong, a more comprehensive approach may be desirable. Evaluations should include not only quantifiable indicators but also qualitative assessments. The latter can include interviews with providers, women, men and community leaders to determine their knowledge of services and eligibility, their perceived need for services, and their views about existing services.

5

Financing

Health service budgets should include costs of: Instruments, supplies and medications needed to begin offering abortion or to improve existing services throughout the system (see Chapter 2) Staff time (whether part time or full time) Training programmes One-time (usually modest) capital costs such as renovating a treatment space.

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Because safe abortion services do not require additional skills or equipment from those that should already be available for obstetrical and gynaecological care, the additional costs of making such services available to eligible women are likely to be modest given the gains for women's health. Most national health budgets should be able to cover these costs. If user fees, medical insurance or other cost-recovery measures are applied to abortion care, they must be designed so as not to impede women's access to services. 5.1 COST TO THE FACILITY OR HEALTH SYSTEM

Costs include infrequent, modest capital investments as well as recurrent costs. Examples of infrequent capital costs are purchases of items such as a suction machine, an examination table, a sterilizer or an autoclave; construction or renovation of consultation and treatment rooms. Recurrent costs include those associated with purchasing instruments and supplies that will need to be restocked regularly, such as cannulae, manual vacuum aspirators, drugs, gauze, antiseptic solutions and cold sterilants used for instrument processing; other recurrent costs include ongoing training, staffing and facility operations. As mentioned earlier, most of these items are likely to be available already in facilities serving pregnant women. Decisions about which abortion methods to offer and how to organize services directly influence the cost of providing services and their affordability. Two organizational issues are of particular importance. First, as mentioned earlier, switching from D&C to vacuum aspiration for uterine evacuation is not only

safer for the woman but has been shown to reduce health system costs substantially (Jowett 2000). Vacuum aspiration can be performed in a simple outpatient treatment room by a trained midlevel health worker, whereas D&C requires an operating theatre and a physician. Vacuum aspiration usually requires less medication for pain than D&C because it is less painful (Grimes et al. 1977) and women can leave the health care facility sooner. Second, as the health system effectively informs women to come early in pregnancy, the use of lower-cost, early procedures goes up and that of the costlier later procedures goes down. These and other changes in patient management not only reduce costs but also improve quality of care. 5.2 MAKING SERVICES AFFORDABLE FOR WOMEN

Facilities often set fees for services so high as to make them unaffordable for many women. Some publicly financed programmes that provide other types of health care free to poor women do not cover abortion or pay only for certain types of procedures. In addition, women may be expected to pay substantial "informal charges" (charges made by providers on top of the official health system charges) which, combined with travel expenses and opportunity costs such as time lost from paid employment, pose a barrier many women cannot cross. Practices such as these are likely to cost the health system more money in the long run by increasing the number of women who attempt to induce abortion themselves or go to unsafe providers, and end up hospitalized with serious complications.

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Financing continued

References

Anonymous. (2000) Improving quality and reducing costs in post-abortion care in Peru. Reproductive Health Matters 8:189. Billings DL, Ankrah V, Baird TL, Taylor JE, Ababio KP and Ntow S. (1999) Midwives and comprehensive postabortion care in Ghana. In Huntington D and Piet-Pelon NJ (eds). Postabortion care: lessons from operations research. New York, Population Council, pp 141-158. Billings DL, Moreno C, Ramos C, González de León D, Ramirez R, Martinez LV and Díaz MR. (2002) Constructing access to legal abortion services in Mexico City. Reproductive Health Matters 10(19):87-95. Bradley J, Sikazwe N and Healy J. (1991) Improving abortion care in Zambia. Studies in Family Planning 22:391-394. Brambila C, Langer A, Garcia-Barrios C and Heimburger A. (1999) Estimating costs of postabortion services at Dr Aurelio Valdivieso General Hospital, Oaxaca, Mexico. In Huntington D and Piet-Pelon NJ (eds). Postabortion care: lessons from operations research. New York, Population Council, pp 108-124. Cook R and Dickens B. (2000) Considerations for formulating reproductive health laws. Second edition. Geneva, World Health Organization. (WHO/RHR/00.1) Coyaji K. (2000) Early medical abortion in India: three studies and their implications for abortion services. Journal of American Medical Women's Association 55(Suppl):191-194. Dickson-Tetteh K, Mavuya LM, Gabriel M, Rees H, Billings DL and King TDN. (2000) Abortion care services provided by registered midwives in South Africa: a report on the midwifery training program. Johannesburg, Reproductive Health Research Unit and Ipas. Ekwempu CC. (1990) Uterine aspiration using the Karman cannula and syringe. Tropical Journal of Obstetrics and Gynaecology 8:37-38. El Shafei M, Hassan EO, Mashalli A, Shalan H and El Lakkany N. (1999) Improving reproductive health service by using manual vacuum aspiration in the management of incomplete abortion. Egyptian Society of Obstetrics and Gynecology 25:711-722.

Where fees are charged for abortion, such fees should be matched to women's ability to pay and should not limit access for women who cannot pay, including low-income women and adolescents. Furthermore, all facilities should have procedures in place to ensure that "informal" charges are not imposed by staff. Other steps that can be taken to make abortion services more affordable for women include subsidizing abortion services for poor women with revenue from other services or from higher-income women; reducing fee differentials for abortions performed at different durations of pregnancy and among different methods, so that women can access services that best suit their needs without regard to cost; and providing information about the availability of abortion services and any associated fees, so that women can make decisions based on accurate knowledge of cost. Abortion should never be denied or delayed because of a woman's inability to pay.

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Freedman MA, Jillson D, Coffin RR and Novick LF. (1986) Comparison of complication rates in first trimester abortions performed by physician assistants and physicians. American Journal of Public Health 76:550-554. Greenslade FC, Benson J, Winkler J, Henderson V, Wolf M and Leonard A. (1993) Summary of clinical and programmatic experience with manual vacuum aspiration. IPAS Advances in Abortion Care 3(2):1-4. Grimes D, Schulz KF, Cates W and Tyler CW. (1977) The Joint Program for the Study of Abortion/ CDC: a preliminary report. In Hern W and Andrikopolous B (eds). Abortion in the seventies. New York, National Abortion Federation, pp. 41-46. Jowett M. (2000) Safe motherhood interventions in low-income countries: an economic justification and evidence of cost effectiveness. Health Policy 53:201-228. King TD, Abernathy M, Hord C, Nicholson LA, Benson J and Johnson BR. (1998) A guide to assessing resource use in the provision of postabortion care. Carrboro, Ipas. Lawson HW, Frye A, Atrash HK, Smith JC, Shulman HB and Ramick M. (1994) Abortion mortality, United States: 1972 through 1987. American Journal of Obstetrics and Gynecology 171:1365-1372. Lean TH, Vengadasalam D, Pachauri S and Miller ET. (1976) A comparison of D&C and vacuum aspiration for performing first trimester abortion. International Journal of Gynecology and Obstetrics 14:481-486. Mundigo AI and Indriso C (eds). (1999) Abortion in the developing world. New Delhi, Visitaar Publications for the World Health Organization. Population Council. (2000a) Burkina Faso: postabortion care. Upgrading postabortion care benefits patients and providers. Washington DC, Population Council, Frontiers in Reproductive Health. Population Council. (2000b) Senegal: postabortion care. Train more providers in postabortion care. Washington DC, Population Council, Frontiers in Reproductive Health.

RCOG - Royal College of Obstetricians and Gynaecologists. (2000) The care of women requesting induced abortion. Evidence-based guideline No.7. London, RCOG Press. University of North Carolina. (2001) PRIME postabortion care. Chapel Hill, University of North Carolina, Program for International Training in Health (INTRAH). Veira Villela W and de Oliveira Araujo MJ. (2000) Making legal abortion available in Brazil: partnerships in practice. Reproductive Health Matters 8(16):77-82. World Health Organization. (1999) Abortion in Viet Nam: an assessment of policy, programme and research issues. Geneva, World Health Organization. (WHO/RHR/HRP/IRR/99.2) World Health Organization. (2000) Managing the complications of pregnancy and childbirth: a guide for midwives and doctors. Geneva, World Health Organization. (WHO/RHR/00.7) World Health Organization. (2002a) Making decisions about contraceptive introduction. A guide for conducting assessments to broaden contraceptive choice and improve quality of care. Geneva, World Health Organization. (WHO/RHR/02.11) World Health Organization. (2002b) Essential medicines: WHO model list (12th Edition). Geneva, World Health Organization. Available on-line at: http://www.who.int/medicines/organization/par/edl/expertcomm.shtml World Health Organization. (2002c) Global consultation on adolescent friendly health services. A consensus statement. Geneva, World Health Organization. (WHO/FCH/02.18) World Health Organization and United Nations High Commissioner for Refugees. (2002) Clinical management of survivors of rape. A guide to the development of protocols for use in refugee and internally displaced person situations. Geneva, World Health Organization and United Nations High Commissioner for Refugees. (WHO/RHR/02.08) Yumkella F and Githiori F. (2000) Expanding opportunities for postabortion care at the community level through private nurse-midwives in Kenya. Chapel Hill, University of North Carolina, Program for International Training in Health (INTRAH).

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Legal and Chapter 4 policy considerations

Chapter 1 ­ Making safe abortion services available: the public health challenge Safe Abortion: Technical and Policy Guidance for Health Systems

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Chapter 4 Summary

Unsafe abortion is one of the main causes of maternal mortality and morbidity even though it is legal for a variety of circumstances in almost all countries. This is because safe abortion services are frequently not available even when it would be legal to provide them. The ICPD + 5 review and appraisal process agreed that, in circumstances where abortion is not against the law, "health systems should train and equip health service providers and take other measures to ensure that such abortion is safe and accessible". Understanding the circumstances under which abortion is not against the law, and the related policy considerations, is crucial for implementing this mandate. In almost all countries abortion is allowed at least when there is a threat to the woman's life. The majority of national laws also allow abortion when pregnancy poses a threat to the woman's physical or mental health; many allow it when pregnancy is the result of rape or incest or when there is fetal impairment. Many laws also allow abortion for socioeconomic reasons, and on request by the woman. An enabling policy environment is needed to ensure that every woman legally eligible has ready access to good-quality abortion services. Policies should be geared to achieving positive health outcomes for women, to providing good-quality family planning information and services, and to meeting the particular needs of groups such as poor women, adolescents, rape survivors and HIV-infected women. Policies and programmes should remove barriers to timely provision of services. Such barriers include lack of public knowledge of the law and where to obtain legal abortion services; third-party authorization or notification clauses; hindering and unnecessary conditions or procedures such as waiting periods or lack of privacy; and excessive restrictions on the kinds of health professionals or institutions licensed to provide abortion. Table 4.2 on pages 91-94 lists some common barriers and suggests actions to correct them.

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1

Women's health and international agreements

The great majority of the deaths from unsafe abortion occur in developing countries where abortion is severely restricted by law (Alan Guttmacher Institute 1999). In developing regions (excluding China), 330 deaths occur per 100,000 abortions, a mortality rate that is hundreds of times higher than the rate in developed countries. The rate is highest ­ an estimated 680 deaths per 100,000 procedures ­ in Africa (Alan Guttmacher Institute 1999, World Health Organization 1998). Most Governments have ratified legally-binding international treaties and conventions that protect human rights, including the right to the highest attainable standard of health, the right to non-discrimination, the right to life, liberty and security of the person, the right to be free from inhuman and degrading treatment, and the right to education and information. In consideration of these human rights, Governments agreed in the ICPD+5 review and appraisal process that "...in circumstances where abortion is not against the law, health systems should train and equip healthservice providers and should take other measures to ensure that such abortion is safe and accessible. Additional measures should be taken to safeguard women's health." (United Nations 1999, paragraph 63.iii). A clear understanding of laws on abortion as

well as related policy considerations is required to ensure that all women eligible under the law have access to safe services. Further, the majority of the world's Governments at the 1995 Fourth World Conference on Women agreed they should "...consider reviewing laws containing punitive measures against women who have undergone illegal abortions." (United Nations 1996, paragraph 106).

2

Laws and their implementation

When a pregnancy threatens the woman's life, almost all countries permit abortion to save the woman's life, as indicated in Chapter 1, Figure 1.1 (United Nations Population Division 1999). Nearly two-thirds of countries allow abortion when there is serious risk to the woman's physical or mental health. In more than 40 per cent of countries, additional grounds for permitting abortion are rape or incest; and a similar percentage allow for abortion in cases of fetal impairment. Many women seek abortion because they cannot afford to look after the child. In addition, there are many women ­ and this applies particularly to young, single women ­ for whom continuing a pregnancy would be socially difficult or impossible. In recognition of these problems, one-third of countries allow abortion on economic and/or social grounds. And some twenty-seven per cent of countries allow abortion on request, in recognition that all women seeking abortion face one or more of these problems.

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2

Laws and their implementation continued

Abortion laws began to be liberalized in the first part of the twentieth century when the extent of the public health problem of unsafe abortion started to be recognized. Prosecutions for carrying out abortions began to disappear in the 1930s in some countries. In England, one medical practitioner deliberately provoked a court case against him in order to argue publicly in favour of decriminalization of abortion for public health reasons. Abortion laws began to be liberalized across Europe and in Canada, Cuba, India, the USA, Zambia and in several other countries in the 1960s and 1970s. Many other countries in all regions of the world have continued to reduce restrictions on and prosecutions for abortion, particularly since the mid-1980s (Berer 2000, Rahman et al. 1998). The formulation of laws relating to abortion varies widely across countries, reflecting their diverse historical, political and religious roots (United Nations 2001a, 2001b, 2002). Provisions regarding abortion may be found in the criminal code, in civil law, or in both. In some countries, public health codes or medical ethics codes may contain special provisions that clarify how to interpret an abortion law but in many countries, no formalised interpretation or enabling regulation exists. In other countries, abortion may not be governed by an enacted law, but by a court

interpretation. In a few countries, the existence of multiple texts may make it difficult at times to determine the exact meaning of the law and policy concerning abortion due to multiple or sometimes conflicting provisions. The elaboration and implementation of laws, policies and regulations reflect interpretation and involvement by various actors including courts, parliamentarians, policy-makers and health care providers, at various times. All of these factors affect both the availability of, and women's access to, safe, legal abortion services. Research from a variety of countries indicates that women eligible under the law often are unable to obtain services (Gupte et al. 1997, Iyengar and Iyengar 2002, Koster-Oyekan 1998, Mundigo and Indriso 1999). The reasons include lack of training for providers, provider unwillingness, Government restrictions on types of facilities and providers who can carry out abortion or failure to provide them with the necessary authorization. They can also include a lack of resources for, and commitment to, delivering good-quality services at the primary care level (Berer 2000). In addition, many people ­ both health service providers as well as women ­ simply do not know what the law allows. For instance, in a region of one country where abortion is permitted up to 20 weeks of pregnancy, more than 75 per cent of married women and men were not aware that abortion was legal (Iyengar and Iyengar 2002). In countries with restrictive

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laws, health providers' cautious attitudes combined with often elaborate procedural requirements, are likely to make the approval process complicated and intimidating, particularly for women living in rural areas, young women and those who are illiterate (Alan Guttmacher Institute 1999). There is thus considerable scope in most countries to: review and promote wider understanding of the relevant laws and policies; design and implement comprehensive policies to ensure access to services to the extent the law provides for; identify and remove unnecessary regulatory and administrative barriers to services.

3.1

WHEN THERE IS A THREAT TO THE WOMAN'S LIFE

Almost all countries allow abortion to be performed to save the life of the pregnant woman. Some countries provide detailed lists of what they consider life-threatening situations. These lists are generally meant to provide illustrations of situations that are considered life-threatening, but they are not meant to preclude the doctor's clinical judgement of what is life-threatening for a particular woman. Such lists, however, may be interpreted restrictively, or be considered exhaustive, when in fact they are not. For example, if a list of physical dangers to life is considered exhaustive, that would exclude mental health conditions that are life-threatening. All health personnel should know the high risks of maternal mortality and morbidity from unsafe abortion and they should be able to counsel women about legally allowed options. In some cases, physicians argue that it is necessary to provide a safe abortion because if they did not, the woman would risk her life by going to an unqualified practitioner (Oye-Adeniran et al. 2002). Even where protecting a woman's life is the only allowable reason for abortion, it is essential that providers are trained, that services are available and known, and that treatment for complications of unsafe abortion is widely available along with family planning services.

3

Understanding legal grounds for abortion

It is essential for health professionals, and others such as police or court officers as well as the public, to have accurate information and to understand clearly what is allowed under the law in their country. While legal interpretations will always be specific to each country, some general remarks can be made regarding the circumstances under which abortion is most frequently allowed, as follows (United Nations 2001a, 2001b, 2002).

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3

3.2

Understanding legal grounds for abortion continued

WHEN THERE IS A THREAT TO THE WOMAN'S PHYSICAL OR MENTAL HEALTH

While "physical health" and "mental health" are sometimes separated as grounds for performing abortion, in many countries the law does not specify the aspects of health that are concerned but merely states that abortion is permitted to avert risk of injury to the pregnant woman's health. In such cases, the WHO definition of health ­ "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity" ­ has sometimes been applied (World Health Organization 2001). When "mental health" is specifically mentioned in the law, some countries have interpreted "mental health" to include psychological distress caused by, for example, rape or incest, or by diagnosis of fetal impairment. In other circumstances, countries have also included in the interpretation of a threat to women's mental health, distress caused by detrimental socioeconomic circumstances. 3.3 WHEN PREGNANCY IS THE RESULT OF RAPE OR INCEST

exploitative. For example, they may require that rape be established to the satisfaction of a judge who might require testimony from witnesses to a violation; or they may require that a police officer be convinced that the woman was violated before she obtains permission for the procedure to be undertaken. These requirements, designed to screen out fabricated cases, often discourage women with legitimate grievances from seeking early, safe services. Delays due to judicial or police requirements can lead women to resort to clandestine, unsafe services or such delays can be so long drawn-out that the woman is ultimately denied abortion because her pregnancy is too advanced. In such circumstances, judicial or administrative requirements should be minimized or removed, and clear protocols established for both police and health workers to facilitate prompt referral and access to appropriate care for women (Billings et al 2002, Veira Villela and de Oliveira Araujo 2000). 3.4 WHEN THERE IS FETAL IMPAIRMENT

In many countries, such cases are interpreted as falling within the mental health grounds for abortion. Some countries accept as evidence the woman's report. Others require forensic evidence of sexual penetration, or require evidence that intercourse was involuntary or

This reason is increasingly permitted by countries with otherwise restrictive abortion laws because it is now possible to diagnose such conditions, many of which are considered to be incompatible with life, or independent life of the affected child. In some other countries, no specific reference is made in the law to fetal impairment; rather, mental health grounds are interpreted to include distress caused by diagnosis of fetal impairment.

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3.5

FOR ECONOMIC AND SOCIAL REASONS

Most countries where abortion is permitted on economic and social grounds interpret the law to include the pregnant woman's social and economic environment, whether actual or foreseeable. Some assess whether the woman is in a state of distress as a result of her situation. Some laws include the extension of risk to cover any existing children of her family, that might be caused by an additional child. 3.6 ON REQUEST

permit abortion later in pregnancy in some circumstances or with additional requirements such as approval by two physicians rather than one (Alan Guttmacher Institute 1999, Rahman et al. 1998). 3.8 OTHER LIMITS

A woman is allowed by law to obtain an abortion without giving a reason. Allowing abortion on request has emerged as countries have recognised that women seek abortions on one, and often more than one of the above grounds, and they accept all of these as legitimate. 3.7 LIMITS ON LENGTH OF PREGNANCY

Abortion laws and policies sometimes unnecessarily restrict the kinds of facilities and practitioners allowed to perform abortion. They may also require authorization from other family members. These kinds of requirements, usually created to protect women's health, may have the opposite effect by creating insurmountable obstacles to access (Iyengar and Iyengar 2002, Koster-Oyekan 1998). A law can also specify when abortion is illegal, rather than spelling out when it is legal. For instance, one such law specifies that abortion is illegal if done without the woman's consent; or done without accepted professional standards; or performed in an inadequate facility; or done for profit (Alvarez-Lajonchere 1989).

Saving a woman's life might be necessary at any point during the pregnancy. Performing an abortion on grounds of fetal impairment is also likely to be in the second trimester since most such diagnoses can only be made after 12 weeks. Laws and policies that allow abortion for economic and social reasons, or on request, generally stipulate limits on the length of pregnancy. This is often 12 weeks since LMP. Some countries set the limit at 18, 22 or 24 weeks since LMP, while others do not specify length of pregnancy. Laws that include gestational limits usually

4

Creating an enabling policy environment

Policies take various forms and may include statutory regulations, regulations issued by the Ministry of Health, professional guidelines and training guidelines, among others. The central elements of a policy required to ensure access to safe abortion services

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4

Creating an enabling policy environment continued

4.2

CONSTELLATION OF SERVICES

to the extent allowed by law are outlined below. While a comprehensive policy may not be immediately achievable, implementation of the ICPD (United Nations 1995) and ICPD+5 (United Nations 1999) agreements that legal abortion should be safe, ultimately requires action on all the elements listed in sections 4.1-4.7. Existing policies should be examined to ascertain where there are gaps and where improvements are needed. 4.1 GOALS

At a minimum, abortion services should always provide medically accurate information about abortion, and offer non-directive counselling and contraceptive information and services, as well as clinical abortion services (see Chapters 2 and 3 for details). Offering contraceptive information, services and referrals with abortion services, and with treatment for complications of unsafe abortion, helps prevent future unwanted pregnancy and reduce the need for abortion. 4.3 METHODS OF ABORTION

Policies should take account of prevailing national health service conditions and should aim to: minimize the rate of unwanted pregnancy and thus the recourse to abortion by providing good-quality family planning information and services, including emergency contraception; ensure that every woman legally eligible has ready access to safe abortion services; meet the particular needs of groups, such as poor women, adolescents, refugees and displaced women, HIV-infected women and survivors of rape, who may need special outreach and support. In order to reach these goals, policies should address the following issues.

It is preferable to provide a choice of methods suited to health system capability as described in detail in Chapter 2. Even the most highly resource-constrained health systems should be able to provide manual vacuum aspiration safely for early abortion at all appropriate levels of the health care system and to refer women to higher levels of care when needed. Manual vacuum aspiration services should also be widely available to treat women who have complications of unsafe and incomplete abortion. 4.4 RANGE OF PROVIDERS

Laws usually require that abortions be undertaken by licensed medical practitioners. However, laws and policies governing medical procedures nearly always allow others, such as midlevel health care providers (e.g. midwives and nurses), to provide various medical services under supervision of a medical practitioner

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where necessary. Midlevel health workers can be trained to provide safe, early abortion. Training and equipping midlevel workers can help ensure appropriate service availability and accessibility without compromising safety, especially where doctors are few or not readily accessible (see Chapter 3). 4.5 SERVICE FEES

4.7

PUBLIC INFORMATION

Broad health education programmes should include basic information on how pregnancy occurs, the early signs of pregnancy, contraception and where and how to obtain legal abortion services (Table 4.1). While many countries may require time to develop comprehensive policies, all countries can immediately take at least incremental steps to expand access to safe abortion services to the extent allowed by the law and to improve the quality of existing services as indicated below. Table 4.1 Core information for public education Women have the right to decide freely and responsibly if and when to have children without coercion, discrimination or violence Basic reproductive physiology, including how pregnancy happens, its signs and symptoms How to prevent unwanted pregnancy, including where and how to obtain contraceptive methods Circumstances under which abortion is permitted The importance of seeking legal abortion services as early as possible when termination of pregnancy has been decided upon Where and when safe abortion is available, and its cost How to recognize complications of miscarriage and unsafe abortion; when and where to obtain treatment The importance of seeking treatment immediately.

If official and "informal" fees for legal, safe abortion are high, they will increase the risk of recourse to unsafe abortion especially by poor women and others, such as adolescents, who do not have access to cash. Where fees for services and other charges are necessary, these should be kept as low and affordable as possible, and subsidies should be provided for those unable to pay. For public health services, the costs will likely be more than offset by the savings achieved by reducing unsafe abortion and the burden that complications of unsafe abortion impose on health systems. 4.6 HEALTH SYSTEM REQUIREMENTS/QUALITY OF CARE

Chapter 3 discusses curricula and standards, clinical and refresher training, logistics systems, management information systems, technical support services and supervision mechanisms, and health budget provisions. All these should be elaborated in an enabling policy. It is essential that all health system personnel be given the necessary information required to inform women where and how to obtain legal services.

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5

Removing administrative and regulatory barriers

Often, certain regulations and guidance relating to the law may create barriers to accessing legal services. These barriers are not actually specified or required in the law itself. Some barriers evolve simply as a matter of practice and are mistakenly assumed to be legally required. All of these barriers are within the purview of Ministries of Health or professional associations to review and remove in order to ensure access to the extent allowed by the law. Ministries of Health can clarify legal requirements, inform personnel and end "common practices" that constrain access to services allowed by law. Table 4.2 provides examples of administrative, regulatory and other barriers that can be eliminated or modified to improve access to abortion services for eligible women. Depending on the national context, the barriers listed in Table 4.2 may be imposed by regulatory requirements, or simply by administrative procedures. Some of the barriers listed in the left-hand column may have been requirements based on what is now outdated practice. For instance, the use of D&C may have generated restrictions on the types of personnel or institutions allowed to perform abortion that are not necessary when vacuum aspiration is introduced. Other barriers, such as requiring spousal authorization, authorized

fees or waiting periods, are often administrative procedures imposed by providers. In such instances they may not be part of official policy nor required by law, nor are they necessary. The gains for public health from removing the barriers are likely to be considerable. The middle column of Figure 4.2 describes illustrative actions to overcome the barriers. Often these are relatively straightforward, but in some cases, such as supporting public education, careful planning and investment of time and resources will be needed. The tasks implied by the "action" column are elaborated in various parts of this monograph. The third column ­ "rationale" ­ outlines the reasons for taking action, also dealt with in more detail throughout this guidance document.

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Table 4.2 Administrative and regulatory barriers to obtaining safe, legal abortion, and measures to eliminate these barriers Barriers Women and health professionals do not know the law or where to obtain legal abortion services. Possible actions Have governmental and other lawyers research and explain their understanding of the law. Support public education programmes. Include information about the law in training and updates for health professionals. Allow the woman to decide. If authorization is required by law, avoid multiple signatures or approval by a committee; assign responsibility to qualified persons who are readily available in the health system. Revise or remove limits on the length of pregnancy that are not medically or legally required. Rationale Lack of information is a major reason for women's recourse to unsafe abortion. Lack of knowledge about legal grounds for abortion causes providers to limit access.

Authorizations from one or several medical personnel (or sometimes commissions) are required.

Approval by someone other than the woman is not medically indicated (except in rare circumstances when abortion would present a medical risk for the woman). In some countries, for instance, a limit of 8 weeks is put on the performance of manual vacuum aspiration, whereas it can be used safely up to 12 weeks by trained providers. Waiting periods unnecessarily delay care and decrease safety.

Time limits that are not medically indicated or in the law are imposed on length of pregnancy for which abortion is performed.

Waiting period is required between request for and provision of abortion or clients are placed on a waiting list.

Eliminate waiting periods that are not medically required, and expand services to serve all eligible women promptly.

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Table 4.2 Administrative and regulatory barriers to obtaining safe, legal abortion, and measures to eliminate these barriers continued Barriers Spousal authorization, or parental notification or authorization, is required. Possible actions If not required by law, ensure providers do not impose spousal or parental authorization. If required by law, in the case of minor, unmarried women, allow authorization by persons other than a parent, if the minor feels she cannot approach a parent (e.g. when the parent is abusive). Allow all women eligible by law access to abortion services free of discrimination by marital status, age, or any other characteristic not required by law. Train providers not to discriminate, and sanction those who do. Minimize requirements, develop and use clear protocols to facilitate prompt referral and access to appropriate care. Train police, court officials and health care providers to understand the need for prompt and compassionate action and to coordinate their services. To comply with the human right of non-discrimination, extend services that meet safety requirements so that all women eligible under national law have access, irrespective of residence, income or other factors. Rationale Such requirements deter women from seeking timely care and may lead them to risk self-induced abortion or clandestine services.

Certain groups of women are excluded from services by health care providers.

International consensus documents recognise the right of individuals to have access to methods of their choice for regulating fertility which are not against the law.

Rape and incest victims are required to press charges against the aggressor, obtain police reports, court authorization, or complete other medically-unnecessary steps to qualify for abortion.

Juridical requirements delay necessary care and increase the likelihood of unsafe abortion.

Unnecessary restrictions on kinds of facilities that provide abortion limit access for women eligible under national law.

Unnecessarily restricting service locations prevents women from accessing services early, raises costs, and may encourage women to seek care from local but unqualified providers.

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Barriers Standards that over-medicalize abortion are required (e.g. mandatory use of ultrasound, inpatient facilities, general anaesthesia, operating theatre, etc.). Only physicians are trained to provide abortion.

Possible actions Remove requirements not medically indicated. Modify service guidelines and make sure training institutions follow them.

Rationale Over-medicalization raises costs, reduces availability of services, does not improve, and may even reduce, safety and quality of care.

Train midlevel providers to the extent allowed by law.

Especially in situations where doctorpatient ratios are low, this requirement prevents women from accessing services early, raises costs, and leads women to seek care from unqualified providers. Trained, midlevel providers (e.g. midwives) can perform manual vacuum aspiration safely, and provide medical methods of abortion. Professional ethical standards usually require health professionals to refer the woman to another willing and trained provider in the same, or an easily accessible, health facility. Where referral is not possible and the woman's life is at stake, require the health professional to provide abortion in accordance with national law.

Health professionals exempt themselves from abortion care on the basis of conscientious objection, but do not refer the woman to another provider.

Require any health professional who claims conscientious objection to follow professional ethical standards.

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Table 4.2 Administrative and regulatory barriers to obtaining safe, legal abortion, and measures to eliminate these barriers continued Barriers Methods of abortion are limited unnecessarily. Possible actions Introduce all methods suited to the capabilities of the health system. Rationale In some countries, for example, D&C is the only method used even though vacuum aspiration would be safer, less costly, and also suitable at all levels of the health system. Introduction of medical methods in addition to surgical methods would expand access. Lowering fees expands access. The cost of subsidies will likely be offset by savings achieved from reducing unsafe abortion and the cost of managing their complications.

Official and informal fees or other charges reduce access to services, especially by poor women and adolescents who do not have access to funds.

Develop and implement equitable cost-recovery schemes that ensure that those without money can access services. Set fees in line with costs and monitor and stop informal charges. Establish guidelines for confidentiality, train staff, monitor and ensure compliance. Modify record-keeping system so that women's identity is concealed. Ensure private space for counselling so that conversations cannot be overheard.

Confidentiality is not assured.

Confidentiality is a key principle of medical ethics; failure to guarantee confidentiality may lead women to seek an unqualified provider.

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References

Alan Guttmacher Institute. (1999) Sharing responsibility: women, society and abortion worldwide. New York and Washington DC, Alan Guttmacher Institute. Alvarez-Lajonchere C. (1989) Commentary on abortion law and practice in Cuba. International Journal of Gynecology and Obstetrics Supplement 3:93/95. Berer M. (2000) Making abortions safe: a matter of good public health policy and practice. Bulletin of the World Health Organization 78:580-592. Billings DL, Moreno C, Ramos C, González de León D, Ramirez R, Martinez LV and Díaz MR. (2002) Constructing access to legal abortion services in Mexico City. Reproductive Health Matters 10(19):87-95. Gupte M, Bandewar S and Pisal H. (1997) Abortion needs of women in India: a case study of rural Maharashtra. Reproductive Health Matters 5(9):77-86. Iyengar K and Iyengar SD. (2002) Elective abortion as a primary health service in rural India: experience with manual vacuum aspiration. Reproductive Health Matters 10(19):55-64. Koster-Oyekan W. (1998) Why resort to illegal abortion in Zambia? Findings of a community-based study in Western Province. Social Science and Medicine 46:1303-1312. Mundigo AI and Indriso C (eds). (1999) Abortion in the developing world. New Delhi, Vistaar Publications for the World Health Organization. Oye-Adeniran BA, Umoh AV and Nnatu SNN. (2002) Complications of unsafe abortion: a case study and the need for abortion law reform in Nigeria. Reproductive Health Matters 10(19):19-22. Rahman A, Katzive L and Henshaw SK. (1998) A global review of laws on induced abortion, 1985-1997. International Family Planning Perspectives 24:56-64.

United Nations. (1995) Report of the International Conference on Population and Development, Cairo, 5-13 September 1994. New York, United Nations. (Sales No. 95.XIII.18) United Nations. (1996) Report of the Fourth World Conference on Women, Beijing, 4-15 September 1995. New York, United Nations. (Sales No. 96.IV.13) United Nations. (1999) Key actions for the further implementation of the Programme of Action of the International Conference on Population and Development. New York, United Nations. (A/S-21/5/Add.1) United Nations. (2001a) Abortion policies: a global review. Volume I Afghanistan to France. New York, United Nations. (ST/ESA/SER.A/187) United Nations. (2001b) Abortion policies: a global review. Volume II Gabon to Norway. New York, United Nations. (ST/ESA/SER.A/191) United Nations. (2002) Abortion policies: a global review. Volume III Oman to Zimbabwe. New York, United Nations. (ST/ESA/SER.A/196) United Nations Population Division. (1999) World abortion policies 1999. New York, United Nations Population Division. (ST/ESA/SER.A/178) Veira Villela W and de Oliveira Araujo MJ. (2000) Making legal abortion available in Brazil: partnerships in practice. Reproductive Health Matters 8(16):77-82. World Health Organization. (1998) Unsafe abortion: global and regional estimates of incidence of and mortality due to unsafe abortion with a listing of available country data. Geneva, World Health Organization. (WHO/RHT/MSM/97.16) World Health Organization. (2001) Basic documents. Forty-third edition. Geneva, World Health Organization.

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Annex 1 Further reading and resources

American College of Obstetricians and Gynecologists. Domestic violence. ACOG educational bulletin. (2000) International Journal of Gynecology and Obstetrics 71:79-87. Annett H and Rifkin S. (1995) Guidelines for rapid participatory appraisals to assess community health needs. Geneva, World Health Organization. AVSC International. (1995) Postabortion women. In AVSC International. Family planning counseling - a curriculum prototype. New York, AVSC International. AVSC International. (1999) Infection prevention curriculum: a training course for health care providers and other staff of hospitals and clinics. New York, AVSC International. AVSC International. (2000) Infection prevention: multimedia package (Training CD-ROM and reference booklet). New York, AVSC International. Baird DT, Grimes DA and Van Look PFA (eds). (1995) Modern methods of inducing abortion. Oxford, Blackwell Science. Baird T, Castleman LD, Gringle RE and Blumenthal PD. (2000) Clinician's guide for second-trimester abortion. Carrboro, NC, Ipas. Baird TL and Flinn SK. (2001) Manual vacuum aspiration: expanding women's access to safe abortion services. Chapel Hill, NC, Ipas. Baker A. (1995) Abortion and options counseling: a comprehensive reference. Granite City, IL, The Hope Clinic for Women. Bertrand J and Tsui A. (1995) Indicators for reproductive health program evaluation. Chapel Hill, NC, The Evaluation Project. Brazier E, Rizzuto R and Wolf M. (1998) Prevention and management of unsafe abortion: a guide for action. New York, Family Care International. Center for Reproductive Law and Policy. (2000) Making abortion safe, legal, and accessible: a tool kit for action. New York, Center for Reproductive Law and Policy.

Comprehensive abortion care with Ipas MVA Plus TM - Reference manual and trainer's manual. Chapel Hill, NC, Ipas (forthcoming). Consortium for Emergency Contraception. (2000) Emergency contraceptive pills: medical and service delivery guidelines. Seattle, Consortium for Emergency Contraception. Consortium for Emergency Contraception. (2000) Expanding global access to emergency contraception. A collaborative approach to meeting women's needs. Seattle, Consortium for Emergency Contraception. Cook R and Dickens B. (2001) Advancing safe motherhood through human rights. Geneva, World Health Organization. (WHO/RHR/01.5) Cook RJ, Dickens BM and Bliss LE. (1999) International developments in abortion law from 1988 to 1998. Amercian Journal of Public Health 89:579-586. Counseling the postabortion patient: training for service providers. Trainer's guide (draft). (1999) New York, AVSC International. DataPAC Core Questionnaire Series. Final Report. (1998) Carrboro, NC, Ipas. (2001) DeBruyn M. (2001) Violence, pregnancy and abortion: issues of women's rights and public health. A review of worldwide data and recommendations for action. Chapel Hill, NC, Ipas. Dickson-Tetteh K, Gabriel M, Rees H, Gringle R and Winkler J. (1998) Abortion care manual: a guide for the training of registered midwives in termination of pregnancy, management of incomplete abortion and related reproductive health matters. Johannesburg, Reproductive Health Research Unit and Ipas. Foreit R and Frejka T (eds). (1998) Family planning operations research. New York, Population Council. Gerhardt AJ, Hausknecht R, Baird TL and Shochet T. (2000) Manual vacuum aspiration. Slide presentation on one compact disc. New York, Physicians for Reproductive Choice and Health. Germain A and Kim T (1998) Expanding access to safe abortion: strategies for action. New York, International Women's Health Coalition.

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Hord CE. (2001) Making safe abortion accessible: a practical guide for advocates. Chapel Hill, NC, Ipas. Hord CE, Baird TL and Billings DL. (1999) Advancing the role of midlevel providers in abortion and postabortion care: a global review and key future actions. Issues in Abortion Care No. 6. Carrboro, NC, Ipas. Huber D. (1997) Postpartum and postabortion contraception: a comprehensive training course. Watertown, MA, Pathfinder International. Paul M, Lichtenberg ES, Borgatta L, Grimes D and Stubblefield PG (eds). (1999) A clinician's guide to medical and surgical abortion. Philadelphia, Churchill Livingstone. Pereira IG and Novaes da Mota C. (2000) Manual para o estabelecimento de um servico de atendimento para aborto previsto por lei [Manual for establishing services for providing abortion foreseen by law]. Carrboro, NC, Ipas. Physicians for Reproductive Choice and Health. (1999) Medical abortion slide and lecture presentation. New York, Physicians for Reproductive Choice and Health. Policar MJ and Pollack AE. (1995) Clinical training curriculum in abortion practice. Washington, DC, National Abortion Federation. Reproductive Health for Refugees Consortium. (1997) Refugee reproductive health needs assessment field tools. New York, RHR Consortium. Reproductive Health for Refugees Consortium. (1998) Five-day training program for health personnel on reproductive health programming in refugee settings. New York, RHR Consortium. Rinehart W, Rudy S and Drenna M. (1998) GATHER guide to counseling. Population Reports, Series J, No. 48. Baltimore, Johns Hopkins University School of Public Health, Population Information Program.

Santana F, Sloan NL, Schiavon R, Billings D, King T, Pobia, B and Langer A. (2000) Guidelines and instructions for monitoring and evaluation of postabortion care services (electronic version 1.0). New York, The Population Council. Solter C, Farrell B and Gutierrez M. (1997) Manual vacuum aspiration: a comprehensive training course. Watertown, MA, Pathfinder International. Talluri-Rao S and Baird TL. (1999) Counseling and information guide for medical abortion ­ with training guide. Chapel Hill, NC, Ipas. United Nations Office of the High Commissioner for Human Rights. For further information related to International Human Rights Covenants, Conventions and other documents see: www.unhchr.ch. Varkey SJ, Fonn S and Ketlhapile M. (2001) Health workers for choice: working to improve quality of abortion services. Johannesburg, Women's Health Project, University of the Witwatersrand. WHO Certification scheme on the quality of pharmaceutical products moving in international commerce. For online information see www.who.int/medicines/library/dap. Winkler J and Gringle R. (1999) Postabortion family planning: a two day curriculum for improving counseling and services. Chapel Hill, NC, Ipas. Wolf M and Benson J. (1994) Meeting women's needs for postabortion family planning: report of a Bellagio technical working group. International Journal of Gynecology and Obstetrics 45 (Supplement). World Health Organization. (1995) Complications of abortion: technical and managerial guidelines for prevention and treatment. Geneva, World Health Organization. World Health Organization. (1996) Studying unsafe abortion: a practical guide. Geneva, World Health Organization. (WHO/RHT/MSM/96.25)

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Annex 1 Further reading and resources continued

World Health Organization. (1997) Post-abortion family planning: a practical guide for programme managers. Geneva, World Health Organization. (WHO/RHT/97.20) World Health Organization. (1999) Interpreting reproductive health. Geneva, World Health Organization. (WHO/CHS/RHR/99.7) World Health Organization. (2000) Strengthening the provision of adolescent friendly health services to meet the health and development needs of adolescents in Africa. A consensus statement. Geneva, World Health Organization. (WHO/FCH/CAH/01.16 and AFR/ADH/01.3) Yordy L, Leonard AH and Winkler J. (1993) Manual vacuum aspiration guide for clinicians. Carrboro, NC, Ipas.

Annex 2 International consensus documents in relation to safe abortion

In recent decades, international understanding of the basic civil, social and economic rights with which all people are born has deepened and been progressively articulated in international covenants, treaties and other instruments. Such agreements create a solid basis for real improvements in people's lives, as ratifying nations commit themselves to uphold the rights enumerated therein, including by adjusting laws and policies. The series of International Conferences which took place during the decade of the 1990s developed documents which elaborate on the aspects of reproductive health. These international consensus documents which have been adopted by the majority of countries have the backing of the Human Rights Treaty Bodies' framework, and have been most explicit in articulating rights in relation to reproductive health. Below are statements from recent international consensus documents that highlight issues relevant to safe abortion. 1974 World Population Conference, Bucharest Plan of Action "All couples and individuals have the basic right to decide freely and responsibly the number and spacing of their children and to have the information, education and means to do so." Paragraph 14(f)

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1984 Recommendations for the Further Implementation of the World Population Plan of Action, Mexico City "The World Population Plan of Action recognizes, as one of its principles, the basic human right of all couples and individuals to decide freely and responsibly the number and spacing of their children. For this right to be realized, couples and individuals must have access to the necessary education, information and means to regulate their fertility, regardless of the overall demographic goals of the Government." Paragraph 24 1994 Programme of Action Adopted at the International Conference on Population and Development, Cairo "Advancing gender equality and equity and the empowerment of women ... and ensuring women's ability to control their own fertility are cornerstones of population and development-related programmes." Principle 4 "Reproductive health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity, in all matters relating to the reproductive system and to its functions and processes. Reproductive health therefore implies that people are able to have a satisfying and safe sex life and that they have the capability to reproduce and the freedom to decide if, when and how often to do so.

Implicit in this last condition are the rights of men and women to be informed and to have access to safe, effective, affordable, and acceptable methods of family planning of their choice, as well as other methods of their choice for regulation of fertility which are not against the law..." Paragraph 7.2 "[R]eproductive rights embrace certain human rights that are already recognized in national laws, international human rights documents and other consensus documents. These rights rest on the recognition of the basic right of all couples and individuals to decide freely and responsibly the number, spacing and timing of their children and to have the information and means to do so, and the right to attain the highest standard of sexual and reproductive health. It also includes their right to make decisions concerning reproduction free of discrimination, coercion and violence ... The promotion of the responsible exercise of these [reproductive] rights should be the fundamental basis for government- and community-supported policies and programmes in the area of reproductive health, including family planning." Paragraph 7.3 "[G]overnments should make it easier for couples and individuals to take responsibility for their own reproductive health by removing unnecessary legal, medical, clinical and regulatory barriers to information and to access to family-planning services and methods." Paragraph 7.20

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Annex 2 International consensus documents in relation to safe abortion continued

"In no case should abortion be promoted as a method of family planning. All Governments and relevant intergovernmental and non-governmental organizations are urged to strengthen their commitment to women's health, to deal with the health impact of unsafe abortion* as a major public health concern and to reduce the recourse to abortion through expanded and improved family planning services. Prevention of unwanted pregnancies must always be given the highest priority and all attempts should be made to eliminate the need for abortion. Women who have unwanted pregnancies should have ready access to reliable information and compassionate counseling. Any measures or changes related to abortion within the health system can only be determined at the national or local level according to the national legislative process. In circumstances in which abortion is not against the law, such abortion should be safe. In all cases women should have access to quality services for the management of complications arising from abortion. Postabortion counseling, education and family planning services should be offered promptly which will also help to avoid repeat abortions. *Unsafe abortion is defined as a procedure for terminating an unwanted pregnancy either by persons lacking the necessary skills or in an environment lacking the minimal medical standards or both. (WHO)" Paragraph 8.25

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1995 Fourth World Conference on Women, Beijing "The human rights of women include their right to have control over and decide freely and responsibly on matters related to their sexuality, including sexual and reproductive health, free of coercion, discrimination and violence. Equal relationships between women and men in matters of sexual relations and reproduction, including full respect for the integrity of the person, require mutual respect, consent and shared responsibility for sexual behaviour and its consequences." Paragraph 96 "Governments, in collaboration with non-governmental organizations and employers' and workers' organizations and with the support of international institutions [should]: j. Recognize and deal with the health impact of unsafe abortion as a major public health concern, as agreed in paragraph 8.25 of the Programme of Action of the International Conference on Population and Development; k. In the light of paragraph 8.25 of the Programme of Action of the International Conference on Population and Development... consider reviewing laws containing punitive measures against women who have undergone illegal abortions." Paragraph 106

1999 Key Actions for the Further Implementation of the Programme of Action of the International Conference on Population and Development "(i) In no case should abortion be promoted as a method of family planning. All Governments and relevant intergovernmental and non-governmental organizations are urged to strengthen their commitment to women's health, to deal with the health impact of unsafe abortion as a major public-health concern and to reduce the recourse to abortion through expanded and improved family planning services. Prevention of unwanted pregnancies must always be given the highest priority and every attempt should be made to eliminate the need for abortion. Women who have unwanted pregnancies should have ready access to reliable information and compassionate counselling. Any measures or changes related to abortion within the health system can only be determined at the national or local level according to the national legislative process. In circumstances where abortion is not against the law, such abortion should be safe. In all cases, women should have access to quality services for the management of complications arising from abortion. Post-abortion counselling, education and family planning services should be offered promptly, which will also help to avoid repeat abortions. (ii) Governments should take appropriate steps to help women avoid abortion, which in no case should be promoted as a method of family planning, and in all

cases provide for the humane treatment and counselling of women who have had recourse to abortion. (iii) In recognizing and implementing the above, and in circumstances where abortion is not against the law, health systems should train and equip health-service providers and should take other measures to ensure that such abortion is safe and accessible. Additional measures should be taken to safeguard women's health." Paragraph 63 2000 Further Actions and Initiatives to implement the Beijing Declaration and the Platform for Action "Design and implement programmes with the full involvement of adolescents as appropriate, to provide them with education, information and appropriate, specific, user-friendly and accessible services without discrimination to address effectively their reproductive and sexual health needs taking into account their right to privacy, confidentiality, respect and informed consent and the responsibilities, rights and duties of parents and legal guardians to provide in a manner consistent with the evolving capacities of the child appropriate direction and guidance in the exercise by the child of the rights recognized in the Convention on the Rights of the Child and in conformity with CEDAW and ensuring that in all actions concerning children, the best interests of the child are a primary consideration." Paragraph 115fbis

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Annex 3 Instruments and supplies for manual vacuum aspiration (MVA)

Basic Supplies intravenous infusion set and fluids (sodium lactate, glucose, saline) aspirators (syringes) (5, 10 and 20 ml) needles (22 gauge spinal for paracervical block; 21 gauge for drug administration) sterile gloves (small, medium, large) cotton swabs or gauze sponges water-based antiseptic solution (not alcohol-based) detergent or soap clean water chlorine or glutaraldehyde for disinfection/decontamination high-level disinfection or sterilization agent

Instruments and Equipment vaginal speculum tenaculum sponge (ring) forceps or uterine packing forceps Pratt or Denniston dilators: sizes 13 to 27 French container for antiseptic solution strainer (metal, glass, or gauze) clear glass dish for tissue inspection Medications analgesia medication (e.g. acetaminophen, ibuprofen, or pethidine) anti-anxiety medication (e.g. diazepam) anaesthetic ­ chloroprocaine (1-2%) or lidocaine (0.5-2%) without epinephrine oxytocin 10 units or ergometrine 0.2mg MVA Instruments vacuum aspirator flexible cannulae of different sizes adapters, if needed silicone for lubricating syringes, if needed

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Annex 4 Contraception following abortion

Method Oral Contraceptives (combined and progestogen-only pills) Timing after Abortion can start combined or progestogenonly pill use immediately, including on the day of procedure Remarks if adequate counselling and informed decision-making cannot be guaranteed, delay starting pills and provide condoms in the meantime no protection against STI/HIV infection can be started immediately, even if infection is present Injectables (DMPA, NET-EN, Cyclofem and Mesigyna) may be given immediately if adequate counselling and informed decision-making cannot be guaranteed, delay first injection and provide condoms in the meantime no protection against STI/HIV can be started immediately, even if infection is present Implants may be given immediately if adequate counselling and informed decision-making cannot be guaranteed, delay insertion and provide condoms in the meantime access to a provider skilled in insertion and removal is necessary no protection against STI/HIV can be started immediately, even if infection is present

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Annex 4 Contraception following abortion continued

Method IUD Timing after Abortion IUDs can be inserted if risk or presence of infection can be ruled out delay insertion until serious injury is healed, haemorrhage is controlled and acute anaemia improves Remarks if adequate counselling and informed decision-making cannot be guaranteed, delay insertion and provide condoms in the meantime access to a provider skilled in insertion and removal is necessary no protection against STI/HIV there is some concern about a greater risk of expulsion after second trimester abortion uterine perforation can occur during insertion if infection is present, IUD should not be inserted for at least 3 months after abortion procedure Condoms (male or female) start as soon as intercourse is resumed good interim method if another method is chosen but cannot be started immediately; good continuing method if used consistently and correctly male condom is the only method proven to provide protection against both pregnancy and STI/HIV female condom helps to protect against HIV/STI, but may be less effective than the male condom

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Method Spermicides (foam, cream, film, jelly, suppositories, tablets)

Timing after Abortion start as soon as intercourse is resumed

Remarks possible interim method if initiation of another method must be postponed substantially less effective than other methods no protection against STI/HIV

Barrier Methods (diaphragm used with spermicide; cervical cap)

diaphragm can be fitted immediately after first trimester abortion after second trimester abortion, diaphragm fitting should be delayed until uterus returns to pre-pregnancy size (in 6 weeks) fitting of cervical cap should be delayed until uterus returns to pre-pregnancy size (4-6 weeks)

diaphragm fitted prior to a second trimester abortion may be too small immediately after procedure due to change in the vaginal tissue and/or cervix diaphragm may provide some protection against STIs; protection against HIV should not be assumed

Fertility Awareness-Based Methods

not recommended for immediate post-abortion use women can use as soon as they have completed 3 post-abortion menses

effectiveness is highly dependent on proper use no protection against STI/HIV

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Annex 4 Contraception following abortion continued

Method Tubal Occlusion Timing after Abortion tubal occlusion (mini laparotomy or laparoscopy) can be performed immediately after an uncomplicated abortion in cases of post-abortal sepsis or fever, severe post-abortal haemorrhage, severe trauma to the genital tract, or acute haematometra, the procedure must be delayed until satisfactory treatment has been completed and/or injury has healed Emergency Contraceptive Pills (levonorgestrel-only and combined estrogen-progestogen regimens) can be used as soon as unprotected intercourse takes place Remarks adequate counselling and informed decision-making and consent must take place before voluntary sterilization procedures (tubal occlusion or vasectomy) no protection against STI/HIV

not suitable as regular method of contraception important back-up method following unprotected intercourse no protection against STI/HIV

Source: The information in this table is based on: World Health Organization. (2000) Improving access to quality care in family planning - Medical eligibility criteria for contraceptive use. Second edition. Geneva, World Health Organization. (WHO/RHR/00.2)

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In June 1999, a United Nations General Assembly Special Session reviewed and appraised progress toward implementation of the Programme of Action of the International Conference on Population and Development (ICPD) held in Cairo, 1994. At this Special Session, the Governments of the world again recognised unsafe abortion as a major public health concern, and pledged their commitment to reduce the need for abortion through expanded and improved family planning services. They also agreed that, "in circumstances where abortion is not against the law, health systems should train and equip health-service providers and should take other measures to ensure that such abortion is safe and accessible. Additional measures should be taken to safeguard women's health." This technical and policy guidance publication is the outcome of a Technical Consultation, of an extensive review of evidence, and of additional review by experts from around the world in the fields of medicine, social science, law, ethics, provision of services and information, and health policy. The publication should be of use to a wide range of health professionals, and others, inside and outside governments, who are working to reduce maternal mortality and morbidity. It provides a comprehensive overview of the many actions that can be taken to ensure access to good quality abortion services as allowed by law.

World Health Organization 20 Avenue Appia 1211 Geneva 27, Switzerland www.who.int/reproductive-health

Contraception 74 (2006) 66 ­ 86

Review article

Review of medical abortion using mifepristone in combination with a prostaglandin analogue

Christian Fialaa,b,4, Kristina Gemzell-Danielssonb

b a Gynmed Clinic, Mariahilferguertel 37, A-1150 Vienna, Austria Division for Obstetrics and Gynaecology, Department of Woman and Child Health, Karolinska Institutet, SE-17176 Stockholm, Sweden Received 10 March 2006; revised 29 March 2006; accepted 31 March 2006

Abstract Induced abortion is still a major health problem in the world and the most frequently performed intervention in obstetrics and gynecology with an estimated total of 46 million worldwide each year. Medical abortion with mifepristone and prostaglandin was first introduced in 1988 and is now approved in 31 countries. This combination of drugs has recently been included in the List of Essential Medicines by the World Health Organisation. The present review summarizes the development, physiology and the development of the currently used regimens. D 2006 Elsevier Inc. All rights reserved.

Keywords: Medical abortion; Mifepristone; Misoprostol; Gemeprost; Review

1. Introduction 1.1. Development of medical abortion during early pregnancy Summary: The discovery of mifepristone has made a major improvement in medical abortion and is now available in 31 countries. Inducing abortion of an unwanted pregnancy by administering drugs is not a new concept. Historic documents list an incredibly large number of drugs and other substances, which women have swallowed or inserted vaginally with the intention of inducing abortion of an unwanted pregnancy [1,2]. However, most of these drugs have been either ineffective as an abortifaciant or dangerous to the health and/or even the life of the women. The discovery of prostaglandins (PGs) has been an important step in the development of safer methods. The first studies were performed using intraamniotic injection of PG, which offered an advantage over hypertonic saline, the standard of that time [3]. However, these methods were only suitable for inducing abortion in the second trimester. Very quickly, a vaginally applicable PG was developed, which gave satisfying efficacy also during early pregnancy [4]. But

4 Corresponding author. Gynmed Clinic, Vienna, Austria. E-mail address: [email protected] (C. Fiala). 0010-7824/$ ­ see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2006.03.018

the drawback of the PG analogues available at that time, i.e., associated pain and gastrointestinal side effects, were major obstacles for widespread use. The turning point came when the French scientist Etienne-Emile Baulieu and colleagues from the French national institute INSERM and a group of colleagues at the French pharmaceutical company Roussel-Uclaf developed mifepristone or RU-486, as it was initially called [5] The abortifaciant potential of mifepristone was described for the first time in May 1982 [6]. This, together with a dosefinding study performed in Stockholm and Szeged in Hungary, indicated that mifepristone is a promising abortifaciant drug with very few side effects [7]. However, it became clear that mifepristone had a maximal effectiveness b 80% when used alone, which was not sufficiently effective to be used as an abortifaciant drug in clinical routine. This low efficacy was confirmed by other studies [8­13]. The final breakthrough came with the discovery that mifepristone increased the sensitivity of the pregnant myometrium to PG, which allowed use of a reduced dose of PG [14]. The maximal effect of the sensitization was seen when the interval between mifepristone and the PG analogue was 36­ 48 h. This led to the development of a combined treatment using mifepristone followed by a PG analogue [12,14 ­16]. A protocol for medical abortion was developed from these findings, consisting of a single 600-mg oral dose of mifepristone (Europe) or repeated low doses of mifepristone

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(China), followed by an appropriate dose of a PG analogue 36­ 48 h later. The high efficacy in terminating early pregnancy and the low rate of side effects of this combined regimen were subsequently confirmed in several large multicenter studies [17­19]. Medical abortion was first approved in France in 1988 (up to 49 days of amenorrhoea), followed by approvals in the United Kingdom (1991) and Sweden (1992) (up to 63 days in both countries). Mifepristone has also been used in China since 1992. However, it was not until 1999/2000 that medical abortion with mifepristone and PG was approved in several other European countries and the United States. Today, mifepristone is marketed in 31 countries worldwide (Fig. 1). The approved protocol includes the association of 600-mg oral mifepristone with 400-Ag oral misoprostol for use up to 49 days of gestation in all countries except the United Kingdom. In Sweden and Norway, the approved protocol also includes giving mifepristone 600 mg in association with gemeprost 1.0 mg vaginally for use up to 63 days of gestation. In the United Kingdom, gemeprost 1.0 mg following 600 mg of mifepristone up to 63 days of gestation is the only approved regimen. In China, a different protocol is used in most institutions, consisting of mifepristone 25-mg tablets taken twice daily for 3 days, followed by misoprostol 600 Ag po for gestations up to 49 days or 800 Ag vaginally in pregnancies between 50 and 63 days of gestation. However, various regimens with several days of ingestion of mifepristone are also used in China (Linan Cheng, personal communication 2005) [20]. According to the manufacturer, so far, more than 1.5 million women have been treated with mifepristone in Europe since it was first introduced in 1988 (Exelgyn, Paris). The close surveillance of the treatment allows confirmation of the very high safety of this regimen. Furthermore, the World Health Organisation (WHO) has recently included the combination of mifepristone and misoprostol for this indication in the Essential Medicine List [21].

Since introduction of the method, research has largely focused on improving efficacy, defining the optimal type, dose and route of administration of the PG analogue. Many studies have also focused on finding the minimum effective dose of mifepristone needed to induce an abortion. An important reason for reducing the dosage of mifepristone has been the relatively high price: approximately 70 per box of three tablets in Europe and approximately US$270 per box in the United States. However, the approved regimen has undergone only a few changes from the patients' perspective since its first marketing in 1988, for instance, changing the PG from intramuscular sulprostone (Nalador) to vaginal gemeprost (Cervagem) or oral misoprostol (Cytotec). Currently, mifepristone is the only antiprogesterone used clinically to any extent. Before mifepristone became available in the United States, a combined regimen of methotrexate (MTX) and a PG analogue was used and is still in use in Canada because mifepristone is not on the market there. So far, no randomized control trial (RCT) has been published, comparing MTX plus PG to mifepristone plus PG. Results of different studies show a lower efficacy for the regimen with MTX, as well as a longer duration until complete abortion and a higher incidence of continuing pregnancies [22]. MTX is also teratogenic. Therefore, WHO and other authorities do not recommend MTX for medical abortion of an intrauterine pregnancy.

2. Mifepristone 2.1. Mode of action Summary: Mifepristone as well as its metabolites are antagonists to progesterone binding to its receptor. Mifepristone is a 19-norsteroid substituted at the 11h position by a p-(dimethylamino)phenyl group. A hydrophobic 17a-substituent increases the binding affinity to the

Fig. 1. World map of mifepristone approval (source: www.gynuity.org).

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progesterone receptor (PR) [23]. A glycin at position 722 in the hormone-binding domain of human PR is critical for mifepristone binding [24]. Like progesterone, mifepristone enters the target cell and interacts with receptors that are largely loosely bound in the nucleus. No metabolization of mifepristone in target cells has been detected [25]. The steroid receptor­antagonist complex also binds tightly to progesterone response elements, but these DNA-bound receptors are transcriptionally inactive if progesterone is present. Mifepristone binds with high affinity to the PR. Its binding affinity for the PR is 2.5­5 times that of progesterone [26,27]. Mifepristone is regarded as an almost pure progesterone antagonist, but a slight agonistic action has been reported [13,28 ­30]. It has been suggested that in the absence of progesterone, the steroid receptor­mifepristone complex may be transcriptionally active on some genes, and mifepristone thus acts as a bpartial agonist Q [31]. When mifepristone is used to terminate pregnancy, one finds a failure to respond in about 1% of the women. It has been suggested that this may be due to a genetic variation in the PR [32]. Mifepristone also binds to the glucocorticoid receptor, with a binding affinity three times that of dexamethasone. To a lesser extent, it also binds to the androgen receptor but not to the estrogen or mineralcorticoid receptor. Three metabolites of mifepristone have a lower affinity to the PR, ranging from 21% to 50%, relative to 100% for progesterone, or 9­21% compared to mifepristone [26,33,34]. The data on pharmacokinetics and binding affinity suggest that these metabolites may contribute to a significant extent (23 ­ 33%) to the antiprogestagenic effects of mifepristone. Thus, the biological actions of mifepristone seem to be induced by the combined pool of mifepristone plus its metabolites [34,35]. 2.2. Uterine contractility Summary: Mifepristone reverses the action of progesterone in pregnancy. It increases uterine contractility, but most importantly, it sensitizes the myometrium to PGs. During early human pregnancy, uterine contractility is suppressed. Csapo et al. [36] showed that lutectomy before the luteoplacental shift, and the subsequent decrease in plasma progesterone resulted in increased uterine contractions and spontaneous abortion. It was proposed that the degree of uterine activity during pregnancy is regulated by the balance between the intrinsic suppressor, progesterone and the stimulant PG F2a (PGF2a) [37]. Progesterone suppresses uterine contractions by inducing hyperpolarization of the cell membrane, which makes the myocytes less sensitive to electrical stimulation. Furthermore, progesterone induces inhibition of gap-junction formation, which counteracts coordinated uterine contractions. In addition, progesterone also has effects on the cervix and the decidua. Treatment with mifepristone counteracts these effects of progesterone. Mifepristone reverses the hyperpolarization of the cell membrane and the progesterone-induced inhibition in gap-junction formation [38]. Following treatment with

mifepristone, there is also an increase in decidual PG release and a reduced activity of PG dehydrogenase [39]. Of decisive importance for the use of mifepristone was the discovery made in 1985 when the combined effect of mifepristone and a PG analogue on uterine contractility was investigated in early pregnancy (Fig. 2) [14]. The authors showed that mifepristone increases uterine contractility and sensitizes the myometrium to PG. The maximum effect was achieved when PGs were administered 36 ­ 48 h after mifepristone and the dose of PGs could be five times lower than used without mifepristone, thus reducing side effects [16]. This effect of mifepristone could also be observed in the nonpregnant uterus [40,41]. However, no effect on cervical priming was observed in nonpregnant women in another study [42]. 2.3. Pharmacokinetics Summary: Oral absorption of mifepristone is rapid with a half-life of 20 ­40 h. When mifepristone is administered orally, absorption is rapid with peak concentrations after 1­3 h, irrespective of dose. Following oral administration of a single dose of 600 mg, the peak plasma concentration of 2.5 Amol/l occurs approximately 90 min after ingestion [27,43,44]. Thereafter, concentrations decrease slowly with an elimination half-life of 20­ 40 h. Although the absorption of mifepristone per os is high (about 70%) its bioavailability is reduced to about 40% due to first-pass metabolism by the liver [13]. Absorption following vaginal application has been shown to be insufficient for any clinical effect [45]. In serum, mifepristone binds to a1-acid glycoprotein (AAG), but it does not bind to transcortin or sexual hormonebinding globulin [26,27]. The presence of AAG in the human may partly explain the differences in pharmacokinetic behavior of mifepristone between the human and other mammalian species [46]. The binding capacity of AAG is saturated by 2.5-AM/l mifepristone, which leads to nonlinear

Fig. 2. Uterine contractility after PG without (A) and with pretreatment of mifepristone (B) [adapted from Contraception 1985;32:45­51].

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kinetic behavior. Doses of mifepristone exceeding 100 mg do not lead to higher plasma levels [47,48]. Furthermore, there is no difference in serum profiles between men, nonpregnant and pregnant women, or between morning and evening administration of the drug [13,49]. When the concentration of mifepristone exceeds the binding capacity of AAG, it becomes more susceptible to metabolism. Thus, the serum concentrations of the metabolites increase as a function of the oral dose of mifepristone. Three metabolites of mifepristone have been identified [34,47]. Mifepristone undergoes demethylation to give the monodemethylated (RU 42,633) and didemethylated (RU 42,848) derivatives, as well as hydroxylation of the propynyl group (RU 42,698). In contrast to mifepristone, plasma levels of these metabolites increase dose-dependently and may exceed the level of mifepristone especially in single oral doses of 400 mg or more [27,34]. These metabolites are excreted in the urine (10%) and in the faeces via the billiary system (90%) [46]. 2.4. Regimens Summary: Mifepristone and the PG analogue act synergistically. The efficacy of various regimens depends on the dose of mifepristone and the interval to PG administration, as well as the dose, type and route of administration of the PG. Efficacy is also dependent on the duration of pregnancy. Beyond 49 days of gestation, oral misoprostol is not sufficiently effective. The bioavailability of misoprostol can be increased by vaginal or sublingual administration, avoiding first-pass metabolism by the liver. Medical abortion can be achieved by using either mifepristone or a PG analogue alone [5,17,50,51,52]. However, efficacy is low for sole use for mifepristone, ranging from 60% to 80% [5,17,50]. With repeated doses of gemeprost alone, a success rate of around 95% could be reached and with misoprostol alone up to 90% with an appropriate regimen. Disadvantages of PG analogues are, however, the high rates of pain and gastrointestinal side effects associated with use of the high doses needed [12,22]. The combined regimen offers a higher efficacy with a low rate of side effects. Mifepristone and the PG analogue act in synergy, as has been mentioned previously [14]. Consequently, a change in the available dose or potency of one drug or in the type, route of administration and interval after mifepristone of the PG analogue will impact on the necessary dose of the other and upon the subsequent efficacy and incidence of side effects. A pictorial comparison to a balance is valid, where reducing one side leads to an increase on the other side. The challenge of medical abortion, therefore, is to find the best balance between both drugs involved or, in other words, to find a balance between high efficacy and good tolerance. Economic considerations are also important, especially for developing countries, where medical abortion could help to reduce the terrible consequences of unsafe abortions [53,54]. Research is still ongoing to finding the optimal dose of mifepristone as well as the optimal type,

dose, route of administration of PG and the shortest possible interval between both drugs. Prior to the first marketing in France, dose-finding studies were performed under the auspices of Roussel-Uclaf for termination of pregnancy using mifepristone alone. At doses of 200­ 800 mg, efficacy was shown to be dose-related in the range of 63 ­87%. No increase in efficacy could be observed with doses above 600 mg or with repeated doses [5,17,50]. These data led to the first registered regimen of a single oral dose of 600 mg of mifepristone followed by a PG analogue. Repeated dose of mifepristone followed by a PG analogue has also been shown to be effective and are widely used in China. The clinical advantages of a single-dose regimen outweigh the slightly higher efficacy of a repeated low-dose regimen [55,56]. The single dose is still the approved regimen in all countries where mifepristone is registered, except in China. When medical abortion was first introduced, the main concern was to find a highly effective regimen and, hence, the dosage of mifepristone and the PG may have tended to be higher than necessary. More recently, research has focused on two aspects: ! ! Reducing dose of mifepristone Reducing side effects of the method

Reducing side effects means optimizing dose, route of administration and regimen of the PG analogue. This will be discussed in the following section. The use of a reduced dosage of mifepristone (200 mg) combined with either 600 or 800 Ag of misoprostol given vaginally or orally or gemeprost vaginally has been investigated in several small trials with the number of patients ranging from 100 to 220. The results showed an efficacy above 90% [57 ­ 61]. This led the way for WHO to perform two large multicenter, multinational RCTs with gestations up to 56 days [62,63]. The first study found a similar efficacy of around 94% for 200 and 600 mg of mifepristone when followed by gemeprost 1 mg. The other study compared gemeprost 0.5­1 mg in association with 200 mg of mifepristone and found a similar efficacy of 91.7% and 92.9%, respectively. Another large, double-blind randomized trial with pregnancies up to 63 days compared 0.5 mg gemeprost with 800 Ag misoprostol vaginally after 200 mg mifepristone and found an efficacy of 96.2% vs. 98.7% [64]. A large case report (2000 consecutive abortions up to 63 days of amenorrhea) showed that 200 mg of mifepristone followed by 800 Ag of misoprostol vaginally gave an efficacy of 97.5% [65]. The high efficacy of this regimen has been confirmed in several other studies [64,66 ­69]. This regimen has since become widely used in some countries (Finland, Sweden, United Kingdom, United States). It is also recommended by several clinical guidelines for pregnancies up to 63 days [WHO guidance, Royal College of Obstetricians and Gynaecologists (RCOG) clinical guidelines and National Abortion Federation recommendations] [70 ­72].

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Table 1 Regimens licensed, recommended or used for medical abortion Mifepristone dose Approved: France, 1991; most other European countries and the US, 2000 Approved: UK, 1991; Sweden, 1992; Norway, 2000 Widely used Guidelines RCOG, UK, 2004 [71] 600 mg Prostaglandin Misoprostol Dose and route of administration 400 Ag po Gestational age limit 49

600 mg 200 mg 200 mg

Misoprostol Gemeprost Misoprostol Misoprostol

400 Ag po 1 mg 800 Ag vaginally 800 Ag vaginally 800 Ag vaginally; 400 Ag repeated orally or vaginally after 4 h, if no expulsion 400 Ag po or vaginally 400 Ag po or vaginally; repeated after 3 h if no expulsion 800 Ag vaginally: repeated within 48 h if no bleeding 800 Ag vaginally 400 Ag po

49 63 63 63 50 ­ 63 49 50 ­ 63 63 63 49

ANAES, France, 2001 [86]

200 mg

Misoprostol

PPFA, US, 2005 WHO, 2003 [70]

200 mg 200 mg

Misoprostol Misoprostol

The above studies were carried out using either gemeprost or misoprostol 800 Ag vaginally for gestations b 63 days. Only a few studies have been done in a developed country setting with a reduced dosage of 200 mg of mifepristone and 400 Ag misoprostol given orally [73 ­75]. Misoprostol 400 Ag po is also the approved and the standard dose for pregnancies up to 49 days of gestation. However, efficacy for gestations up to 49 days was around 90% in all three studies. The WHO study found no difference in efficacy between 200 and 600 mg of mifepristone. But some aspects make the results of the WHO study difficult to interpret: ultrasound was not done on a routine basis, neither before nor after treatment; gestational age was estimated on Last Menstrual Period (LMP) and clinical examination; most of the 17 centers had no prior experience with medical abortion in a routine clinical setting and efficacy by center ranged from 77% to 100% among the 50 ­ 100 cases performed by each center [73]. Shannon et al. [75] excluded 12 patients (3.3%) after the treatment because they needed additional misoprostol at or after follow-up. No information is given as to how many of these patients needed curettage, which would have classified the cases as failures [75]. Schaff et al. [74] conducted a large randomized trial comparing the same regimen as the two abovementioned studies, 200 mg mifepristone followed by 400 Ag misoprostol po vs. 800 Ag given vaginally in gestations up to 63 days. However, Schaff et al. prematurely stopped the arm with the 400-Ag oral misoprostol regimen because they judged the success rate too low: 84% overall and 89% in gestations up to 49 days. The group using the higher dose of vaginal misoprostol had an overall success rate of 96% and 97% in gestations up to 49 days [74]. A direct comparison in an RCT has not been done between the approved regimen of 600-mg mifepristone followed by either 400 Ag of misoprostol po or 1-mg

gemeprost vaginally and 200-mg mifepristone followed by 800 Ag of misoprostol vaginally. A further reduction of mifepristone to 50 mg has also been studied in gestations up to 56 days. The result shows the interdependency of both drugs; when one drug is given in a sufficient dose, it can counteract a reduction of the other drug. Efficacy was 89.8% in combination with the standard dose of gemeprost 1 mg but fell to 84.7% with a reduced dose of gemeprost of 0.5 mg [63]. Unfortunately, the published recommendations on regimens differ from each other and from the approved regimen (Table 1). The situation is further complicated by the fact that mifepristone is approved for medical abortion with different gestational age limits in different countries. Also, these limits are not respected in the same manner in all countries. As a result, there is some confusion among clinicians as to which regimen is optimal and approved to use. 3. Prostaglandin analogues in medical abortion Summary: E1 PG analogues like misoprostol or gemeprost have become the standard of care because of better tolerability and higher uterine specificity, as compared to other PG analogues. Today, misoprostol has replaced gemeprost due to a lower rate of side effects and costs. When medical abortion was introduced in France in 1988, in most cases, sulprostone, a PG E2 derivative, was given intramuscularly 36 to 48 h after the administration of 600 mg of mifepristone. Providers applied different doses of sulprostone ranging from 125 to 1000 Ag [17]. Less often, gemeprost, a PG E1, was used intravaginally in a dose of 1 mg [17,76,77]. Gemeprost had been available as a vaginal pessary, licensed for induction of second trimester termination of pregnancy. In the following years, myocardial infarction attributed to coronary spasm induced by sulprostone occurred in three

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patients among the 60,000 women treated with medical abortion [77]. One of them, a 30-year-old multiparous woman who smoked heavily, died due to the infarct [78]. At least one of these three patients had received a dose of sulprostone higher than the recommended dose of 250 Ag [17]. The suspicion that sulprostone had caused the myocardial infarction is further substantiated by a similar report without pretreatment of mifepristone [79]. Following these severe reactions, sulprostone for intramuscular injection was withdrawn from the market and misoprostol 400 Ag po was used instead from 1992 onwards after several studies suggested similar efficacy [77,80,81]. Since introduction of an E1 PG analogue (gemeprost or misoprostol) in association with mifepristone for termination of pregnancy, no cases of myocardial infarct have been reported. Also, the rate of less severe side effects has diminished, as compared to the rate associated with use of sulprostone. After the three cases of cardiovascular adverse events, a contraindication was added to the product label for Mifegyne/ Mifeprex for women over 35 years of age who smoke. This contraindication was added, although the cardiovascular incidences were associated with use of an E2 PG and not with misoprostol or gemeprost, both E1 derivatives. The contraindication was later changed to a warning. However, the product information for misoprostol does not include any reference to age or smoking habits of patients when being used as a continuous therapy for gastric ulcer. Gemeprost has been widely used in early medical abortion. It is easily available in many countries, and gynecologists have a long experience with the drug as it is approved for vaginal application in second-trimester abortion. However, it has several disadvantages compared to misoprostol: ! ! It is only available as 1-mg pessary for vaginal use. The available pessary contains an unnecessarily high dose of PG for very early medical abortion, with dose-related side effects.

! ! !

It is unstable at room temperature, which makes it difficult to store and transport. It is expensive. It is only available in a limited number of countries, in contrast to misoprostol.

These aspects have led to the substitution of gemeprost by misoprostol over the last few years [64]. 3.1. Misoprostol Summary: Misoprostol is the PG analogue of choice for medical abortion. It is a well-known and thoroughly studied drug. It is well tolerated and has few, but dose-dependent, side effects. Misoprostol (15-deoxy-16-hydroxy-16-methyl PG E1) is a PG E1 analogue, developed in 1973 by Searle for the treatment and prevention of gastric ulcer. It received its first marketing authorization in 1985 and is now approved in more than 80 countries, mostly under the brand name of Cytotec (Fig. 3, world map on the approval of misoprostol). It is supplied in tablets containing 200 Ag of misoprostol for oral use. A 100-Ag form is available in some countries. Treatment and prevention of gastric ulcer is still the only licensed indication for misoprostol, with the exception of the recently approved Gymiso in France and a 25-Ag vaginal suppository for induction of labor available in Brazil and Egypt (www.misoprostol.org). Misoprostol has several advantages over other PGs on the market: It has limited effect on the bronchi or blood vessels at the licensed doses used for abortion. It can be stored at room temperature for many years. The oral tablets are effective when administered orally, vaginally, sublingually or rectally. It is inexpensive.

Fig. 3. World map of misoprostol approval (source: www.gynuity.org).

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-

The only side effects of note are diarrhoea and shivering, both of which are dose-dependent and self-limiting.

The use of misoprostol has been extensively studied in the field of reproductive health and it is widely recommended for treatment of missed and incomplete miscarriages, induction of abortion and cervical preparation before uterine instrumentation [51,82]. Misoprostol is also used in late pregnancy for induction of labor and prophylaxis and treatment of postpartum hemorrhage. However, the manufacturer and holder of the patent for misoprostol, Searle (now incorporated into Pfizer), has never applied for licenses for any of the reproductive health indications, despite the abundant literature on its safe and effective use in that field. The reason is probably an effort to avoid potentially damaging discussions about the drug's use for inducing abortion [83]. Despite the lack of an approved indication, misoprostol is specifically mentioned as the PG of choice in the marketing authorization for mifepristone in European countries except the United Kingdom and together with gemeprost in Sweden and Norway. The Food and Drug Administration (FDA) in the United States granted a license for mifepristone in 2000, and the recommended abortion regimen specifies misoprostol as the PG of choice [84]. This has resulted in the unique situation where misoprostol is approved in many countries as part of an abortion regimen but does not hold a registration for abortion in its own right. To reflect this, the FDA has recently changed the labelling of misoprostol so that it is no longer bcontraindicated in pregnancyQ but, rather, that it bshould not be taken by pregnant women to reduce the risk of ulcers induced by nonsteroidal anti-inflammatory drugsQ (NSAIDs) [85]. This move followed the change of the French registration of misoprostol, which now lists pregnancy as a contraindication except in the case of an induced abortion. In the United Kingdom, the RCOG recommends misoprostol for the induction of abortion in association with mifepristone, as done in France by the relevant health ´ authority Agence Nationale d'Accreditation et d'Evaluation ´ en Sante (ANAES), and the British National Formulary has ´ added a paragraph stating, bmisoprostol is given by mouth or by vaginal administration to induce medical abortion (unlicensed indication)Q [71,86,87]. In Sweden and Norway, it is specified in the summary of product characteristics (SmPC) for Mifegyne/Mifeprex that misoprostol 400 Ag po should be given for termination of pregnancy of up to 49 days of amenorrhea or gemeprost 1-mg pessary up to 63 days. Only in 2004 has the first presentation of misoprostol been specifically approved for medical abortion. So far, it is only available in France under the brand name of Gymiso. 3.2. Pharmacokinetics misoprostol Summary: Misoprostol is rapidly absorbed after oral or sublingual intake and has a short half-life of 20­ 40 min.

Plasma levels increase more slowly following vaginal or buccal administration. Sublingual, vaginal and buccal administration results in a longer-lasting elevation in plasma levels compared to oral misoprostol. The effect seems to be shorter-lasting for sublingual than vaginal misoprostol. The latter routes lead to regular uterine contractions in contrast to oral administration. Misoprostol is rapidly and almost completely absorbed after oral administration. It is converted by the liver passage to its pharmacologically active metabolite, misoprostol free acid. Plasma concentrations of misoprostol acid peak in approximately 12 min and decline rapidly thereafter with a terminal half-life of 20 ­ 40 min. The bioavailability of misoprostol is decreased by concomitant ingestion of antacids or food, delaying plasma peak to 20 and 64 min, respectively. However, there is a high variability of plasma levels of misoprostol acid between and within studies (product information of Cytotec) [88,89]. Misoprostol is primarily metabolized in the liver, and less than 1% of its active metabolite is excreted in urine. Misoprostol has no known drug interactions and does not induce the hepatic cytochrome P-450 enzyme system. This very short pharmacokinetic and, therefore, short clinical effectiveness has stimulated research into ways to prolong its activity. One way has been to evaluate different routes of application. Although misoprostol 200-Ag tablets are approved for oral use only, vaginal, sublingual, buccal and rectal application have been shown to be possible and even clinically superior in some cases. Pharmacokinetic studies have shown that the peak concentration is highest after sublingual administration [90], whereas vaginal administration has the advantage of a prolonged time to peak concentration and a slower decrease, as compared to oral administration (Fig. 4) [89 ­ 93]. One problem with vaginal application, however, is the great individual variation of absorption. While the misoprostol from the tablets is mostly very well absorbed, the tablets do not fully dissolve in many cases. Remnants of the tablets can therefore be found in the vagina several hours after application. This might pose a risk for prosecution in countries where abortion is illegal [91].

Fig. 4. Mean plasma concentrations of misoprostol acid over time with oral and vaginal administration [modified from Obstet Gynecol 1997; 90:88­92].

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Furthermore, most women prefer the oral route to vaginal application [94 ­96]. A few clinical studies have been published using repeated dose of misoprostol after 4 ­6 h. So far, there is no published study on plasma misoprostol levels beyond 6 h of administration or after repeated doses. Another approach could be the use of an oral slowrelease misoprostol. Previous studies had shown high rates of side effects due to the PG analogues used at that time [97,98]. Recently, a new misoprostol slow-release formula for oral use has been described [99]. Pharmakocinetics and uterine contractility have shown promising results [100,101]. So far, no clinical studies of this agent for medical abortion have been published. 3.3. Misoprostol alone Summary: Misoprostol alone can induce an abortion, although it is associated with more side effects and a longer induction-to-abortion interval as when combined with mifepristone. The effectiveness and safety of medical abortion using a combination of mifepristone and misoprostol have been well established. However, many women live in countries where they have no easy access to legal abortion [53,54]. Unfortunately, mifepristone is not available in these and other countries (Fig. 1, world map of availability of mifepristone). Very quickly, women and physicians in these countries have realized that misoprostol can be used alone to induce abortion. The use of misoprostol for this indication has been facilitated by the drug's wide availability and low cost. The frequent use of misoprostol for the induction of abortion in some countries has been reported to contribute to an observed decrease in the complications from unsafe abortion [102]. The resulting increased demand for a misoprostol-alone regimen has prompted research to find the regimen with the highest efficacy and the lowest rate of side effects. Different doses, dosage intervals and route of administration have been evaluated (www.misoprostol.org) [103]. However, available data suggest that the effectiveness of misoprostol alone is lower than that seen with the sequential use of mifepristone and misoprostol, even when misoprostol is administered vaginally [103]. Furthermore, the procedure takes longer, requires higher doses of misoprostol and, thus, causes more side effects, such as painful uterine contractions, diarrhea and fever. 3.4. Doses and route of administration of misoprostol Summary: The pharmacokinetics of the approved oral application with short-lasting elevation in plasma levels and weak effect on uterine contractility led to the evaluation of other off-label routes, which proved to have a longer-lasting and more pronounced effect on uterine contractility. An oral dose of 400 Ag of misoprostol, in combination with 600 mg mifepristone, is effective for termination of pregnancy of up to 49 days of gestation and is associated with an acceptable level of PG-related side effects. However, the success rate of this regimen declines with increasing

gestational age and has unacceptable failure rates above 49 days [63,69,104]. The rate of complete abortion with this regimen was shown to be 92%, 83% and 77% for gestational age of less than 49, 50 ­56 and 57­ 63 days, respectively [105]. Another study found similar rates with 89%, 81% and 65%, respectively [74]. Therefore, studies were undertaken to determine if alternative regimens would improve the efficacy of the regimen for medical abortion of pregnancies longer than 49 days of gestation. Efficacy of 800-Ag misoprostol given orally as a single or divided dose after mifepristone to women with pregnancy of up to 56 days of gestation resulted in a sufficiently high level of efficacy (95% and 92% for the single and divided dosage, respectively) [59]. However, side effects were common. This led to the evaluation of vaginal, sublingual and buccal routes for administration of misoprostol, even though the misoprostol 200-Ag tablets are intended and approved for oral use only. Studies on the route of administration and the dose of misoprostol are a major topic in recent and current research. This activity reflects the need for an improved regimen. A slow-release formulation may offer advantages over the currently available formulation of misoprostol. 3.4.1. Vaginal application Summary: Misoprostol given vaginally leads to longerlasting elevations in plasma levels and to the development of regular uterine contractions as compared to oral application. This route of administration has shown clinical benefit and has become the standard of care for gestational age above 49 days of amenorrhea. The vaginal route of administration of misoprostol has been shown to be more potent in medical abortion, compared to oral application. Treatment with 800-Ag misoprostol orally resulted in a significantly higher rate of side effects, compared to the same dose applied vaginally and in more continuing pregnancies in pregnancies up to 63 days of gestation [106]. This has been confirmed in a large number of case series reports. The complete abortion rate in up to 63 days of gestation achieved by using mifepristone, followed by 800 Ag of vaginal misoprostol administered 48 h later, was 95­ 98% [64 ­ 67,107]. Furthermore, three randomized comparative trials were carried out, which compared mifepristone followed by 800 Ag misoprostol given orally or vaginally for termination of pregnancy of up to 63 days of gestation. They showed a complete abortion rate of only 87­90% in the oral group, compared to 95 ­ 97% in the vaginal group. Also, the number of continuing pregnancies was higher following oral treatment, while the incidence of side effects was significantly lower following vaginal treatment [69,108,109]. The increased efficacy associated with use of vaginally administered misoprostol is likely due to a threefold increase in the bioavailability of the drug as well as prolonged exposure of the myometrium when administered by the vaginal route [89,90].

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When the absorption kinetics of oral and vaginal treatment was compared, it was shown that the plasma levels of misoprostol were directly correlated with the effect on uterine tonus. Following administration of misoprostol, the initial increase in uterine tonus was faster and more pronounced after oral administration. However, following vaginal administration, all patients developed uterine contractions that increased continuously during the 4-h observation period and still seemed to increase at the end of recording (Fig. 4). This was not the case after oral treatment [91]. The half-life for misoprostol is about 20­40 min and should be the same following oral or vaginal administration. Thus, the difference in effect on uterine contractility most likely represents a difference in the rate of absorption and metabolism. With vaginal administration, the first-pass liver metabolism can be avoided, and plasma levels remain elevated for a longer period. Prolonged stimulation of the myometrium will result in development of uterine contractions [91]. So far, there are no published RCTs that evaluate a reduced dose of vaginal misoprostol, but such studies are ongoing. When 200 mg of mifepristone was followed by either 0.5 mg of gemeprost or 800 Ag of misoprostol administered vaginally, the efficacy was higher with misoprostol [64]. As mentioned previously, there is currently no formulation of misoprostol 200 Ag available for vaginal use. The only type of misoprostol designed for vaginal use is a 25-Ag pessary for induction of labor, which is on the market in Brazil and Egypt. The widely used 200-Ag tablets are approved for oral use only and not intended for vaginal application. However, a physician is allowed to use a drug in a way not specified in the approval (off-label) if supported by available evidence (EC Pharmaceutical Directive 65/65/EEC) [71,82]. The EC Pharmaceutical Directive 65/65/EEC specifically permits physicians to use blicensed medicines for indications or in doses or by routes of administration outside the recommendations given in the license.Q 3.4.2. Sublingual administration Summary: Sublingual administration leads to regular uterine contractions, similar to the vaginal route, but the effect may be shorter lasting. However, the prevalence of PG-related side effects was higher with this route of administration. The data on buccal use of misoprostol in medical abortion are limited to one study up to 56 days. A drawback of vaginal administration of misoprostol is the fact that the tablets are licensed for oral use only. In addition, most women prefer to take the tablets by mouth [94 ­ 96]. Recently, sublingual administration of misoprostol has been described, and the effect of sublingual misoprostol on uterine contractility has been investigated [110­112]. The authors found regular uterine contractions in all subjects following sublingual and vaginal administration but not after oral administration (Fig. 5). The increase in uterine activity measured in Montevideo units following sublingual and vaginal administration, after 2 h and thereafter, was significantly higher than that seen following oral

Fig. 5. Uterine activity in Montevideo Units induced by misoprostol given at different routes of administration [modified from Obstet Gynecol 1999; 93:275 ­ 80, Ann N Y Acad Sci 1959;75:813­30, Hum Reprod 2004; 19:81 ­ 4].

administration. The development of contractility measured after sublingual administration was very similar to that seen after vaginal administration but decreased faster at 4 h. One inconvenience of sublingual administration is the unpleasant taste, and some women prefer to swallow the pills [112]. The effect of sublingual misoprostol may also be shorter-lasting than that of vaginal misoprostol, but it could be an alternative when vaginal administration is not acceptable [113]. Several studies report an efficacy similar to the vaginal route (96 ­ 99% for gestations up to 63 days) and high acceptability [114]. However, women receiving misoprostol sublingually were more likely to experience diarrhea (p b .01), shivering (p b .01) and unpleasant taste in the mouth (p b.01). 3.4.3. Buccal administration Summary: Recently, buccal administration has been suggested as a new route of administration, but only two studies on this route of administration have been published so far [115,116]. A pharmacokinetic study showed that peak concentration of misoprostol after buccal administration is less pronounced, as compared to sublingual administration [115]. Also, side effects were less pronounced. After these promising results, buccal administration in early medical abortion was evaluated. In another study, the buccal and vaginal routes were compared in gestations up to 56 days. Women received mifepristone 200 mg po and were randomized to use 800 Ag of misoprostol either buccally or vaginally 1­2 days later. Among 429 patients, the efficacy rate was 95% and 93% in the buccal and the vaginal group (p= .51), respectively. Nausea was the most commonly reported side effect, affecting 70% in the buccal group and 62% in the vaginal group. There were no differences in the satisfaction with the overall procedure between the buccal (92%) and the vaginal groups (95%). 3.4.4. Repeated doses Summary: So far, there is insufficient evidence to give an evidence-based recommendation on repeated oral misoprostol in early gestational age.

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Mifepristone followed by repeated doses of misoprostol for termination of early pregnancy was investigated in several studies to determine if dividing the dose would increase the efficacy of medical abortion or reduce the amount and duration of bleeding whilst minimizing the level of side effects. This approach has been successful in the second trimester [117,118]. Different misoprostol regimens have been evaluated, which have included various dosages (200, 400, 600 or 800 Ag), intervals between doses (3, 4, 6­ 8 or 24 h) and the number of doses given [66,68,69,77,108,119 ­122]. A recent study showed that 1 week of misoprostol 400 Ag bid po following mifepristone did not significantly improve efficacy or bleeding patterns, compared to the standard single dose but increased side effects [69,109]. Similarly, the overall efficacy of the procedure was not increased by a single small second dose of misoprostol (200 Ag) approximately 3 h after the first dose. It did, however, shorten the interval to expulsion [104,120]. In another study with 903 women, a larger second dose of misoprostol (400 Ag) was given orally to those women who had not expelled the gestational sac within 3 h after the first dose. In this study the results showed an increase in efficacy from 95.4% to 98.5% and a reduction of treatment failures (ongoing pregnancy) from 1.5% to 0.1%, as compared to the standard single dose of misoprostol [120,123]. Another study with more than 1000 patients found a significant increase in efficacy after a second dose of 800 Ag misoprostol given vaginally to those women with a persistent gestational sac on sonogram on Days 4 ­8, as compared to the single dose [74]. The increase in efficacy was more pronounced in the group receiving misoprostol orally (92% vs. 95%) and less pronounced in the group receiving vaginal misoprostol (96% vs. 98%). A large case series report with 4132 patients compared single-dose treatment of misoprostol following mifepristone in the first 2000 women with giving a second dose of 400-Ag misoprostol 4 h after the first dose to the subsequent 2132 women; both doses were given vaginally. Adding a second dose did not change the overall success rate of 97.8% but led to a significantly lower rate of ongoing pregnancies of 0.2% vs. 0.6% [68]. There is, so far, too little data on repeated doses of misoprostol after mifepristone in early medical abortion to make an evidence-based recommendation. Despite this, some providers use repeated doses either routinely for all patients or in those cases when expulsion or bleeding has not occurred after a certain number of hours. The failure to detect a difference in the available studies should not be interpreted as evidence that repeated misoprostol does not improve effectiveness. However, the success rate of medical abortion is already very high, and any further improvement by giving a second dose would be small. Consequently, the trial could have been underpowered to detect a significant difference.

3.5. Misoprostol taken in the clinic or at home Summary: Home use of misoprostol has been shown to be safe in gestations up to 63 days of amenorrhea and is therefore increasingly offered. However, the approved regimen stipulates taking misoprostol at the provider's facility in most countries. When medical abortion was first introduced in the late 80s and early 90s, patients were monitored closely. Providers had no experience, and the patients did not know what to expect. Patients remained under medical supervision in the clinic during the first few hours following administration of the PG. Consequently, the patients are required to attend more visits at the clinic (usually 3 or 4) for a medical abortion with mifepristone followed by misoprostol than for a vacuum aspiration. This requirement is frequently met with little understanding from the patients who expect a bnaturalQ and bspontaneous abortion-likeQ process. Therefore, bhome use of misoprostolQ was studied in order to avoid the need for the second clinic visit [107,124]. These studies showed that home use is safe from a medical point of view and that patients can cope with the side effects of the treatment. Furthermore, it showed that a majority of patients prefer the privacy of their home environment in which to cope with the vaginal bleeding. These findings were later confirmed by several studies that included women undergoing termination of pregnancy of up to 63 days of gestation [66,67,125,126]. Home use of misoprostol has also been the standard of care with very good results in the French island of Guadeloupe since the early 90s [124]. When medical abortion was introduced in the United States in 2000, home use of misoprostol quickly became the standard of care [Mary Fjerstad, Planned Parenthood, Planned Parenthood of America (PPFA), personal communication]. In contrast, home use of misoprostol is still not offered to most women in Europe except for Sweden and Austria where it has been shown to be highly acceptable to women and their partners [127]. There are currently initiatives in France and the UK to offer home use of misoprostol [128,129].

4. Various aspects of medical abortion 4.1. Acceptance Summary: It has been shown that a free choice of the available methods is highly important for the women. Up to 70% will choose medical abortion, provided they have the option. Medical abortion is not a better method per se than vacuum aspiration. It is just another method with different characteristics [130]. Medical abortion has advantages and inconveniences. The choice of one or the other method depends not so much on medical criteria but, rather, on individual preference. An important factor determining choice of one or another of the methods is speed of access to treatment once the decision to have an abortion has been made [131].

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There are some aspects that limit free choice and acceptance of medical abortion. For example, the number of visits required is still three in most clinics and sometimes four, depending on national regulations on abortion and obligatory waiting period (i.e., France, Germany). Also, women are asked to stay for several hours in the clinic following administration of the PG. Furthermore, some physicians are reluctant to start the treatment in very early pregnancy if they cannot detect fetal cardiac activity on ultrasound. Last, but not least, the reimbursement for medical abortion by the health insurance might be less than for surgical abortion, limiting free choice (i.e., Germany). The uptake of medical abortion has been slow in most countries as a consequence of limited choice for the women [139]. It took about 10 years in France, Scotland and Sweden before 50% of all abortions in the first trimester were carried out using the medical method (Fig. 6). Studies also confirmed that around 50 ­70% of eligible women in early pregnancy will choose medical abortion if they have a truly free choice [94,132]. Positive examples of the introduction of medical abortion are given by Switzerland and Finland; in these countries, fast uptake reflects the flexible medical system, which offered women a free choice after a short introductory period. Training of health care providers has also been shown to be crucial for fast uptake. In order to give patients a free choice of medical or surgical abortion, doctors, midwives and nurses must feel comfortable with the methods and be well informed about all aspects of the treatment. Training of the health care providers is therefore essential when introducing medical abortion. Health care providers who are not actually engaged in performing medical abortion also need to be well informed in order to counsel and to refer their patients properly. Why do women choose medical abortion when the surgical method works so well? The women themselves best answer this question. The following main reasons were given in different surveys [94,133,134]: 1. 2. 3. 4. 5. Avoiding surgery or general anaesthesia Perceived to be safer Perceived to be more natural More privacy and autonomy Less invasive

because abortion per se is associated with a high incidence of psychological benefit, whichever method is used [136]. Another study found that medical abortion is associated with the same low rate of short-term psychiatric morbidity as had previously been recorded following surgical methods [137]. Having a choice between the methods was considered very important and resulted in high levels of acceptability. No significant differences in general, reproductive or psychological health were found between women who had undergone medical abortion or vacuum aspiration 2 years previously [94,138,139]. 4.2. Interval mifepristone­misoprostol Summary: Mifepristone and the PG act in synergy. The optimal sensitization of the myometrium occurs after an interval of 36­ 48 h. After it was discovered that mifepristone sensitizes the myometrium to PG analogues, research was initiated to determine the optimum time interval between administration of the two drugs. In the first study, an interval of 4 days was tried [14]. It was soon discovered that sensitization of the myometrium develops within 24 h. The sensitization further increases until 36­ 48 h after mifepristone, although this later increase was not statistically significant [16]. This finding led to the approved and widely recommended regimen with an interval of 36 ­48 h between mifepristone and misoprostol administration. This finding was later confirmed by a study on the effect of mifepristone on cervical ripening, dilatation and softening. It was shown that the priming effect after 48 h is significantly more pronounced than after 24 h [140]. The study showed that women who received mifepristone 24 h before the operation had a significantly lower baseline cervical dilatation (7.5 mm vs. 8.3 mm; p= .05) and required greater mechanical force to dilate the cervix (cumulative force to 9 mm: 37.7 vs. 23.4 N; p= .03) than did women who received mifepristone 48 h before the operation. Similarly, the mean interval from induction to expulsion in second trimester abortion was significantly shorter when PG was initiated 48 h (6:20 h) after mifepristone as compared to 24 h (7:25 h) [141].

In most studies, between 80% and 95% of women who chose medical abortion found it acceptable and would choose the same method again if they need another abortion in the future. They would also recommend the method to other women who need an abortion [94,96,131,133,135]. This high rate of satisfaction was dependant on women being offered a truly free choice of method. 4.1.1. Long-term acceptability Several studies evaluated the long-term acceptance and well-being of patients following medical abortion. As regards psychological aspects, medical abortion was found to be as safe as surgical vacuum aspiration, mainly

Fig. 6. Percentage of medical abortions among first trimester abortions (Source: national statistics).

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However, waiting for 2 days may be inconvenient for the women concerned as well as for the institution providing the treatment. Therefore, shorter intervals of 24 h and 6 ­8 h have been studied [67,108,142,143]. Efficacy has been high in all these studies, depending on the dose, route of administration and potency of the PG analogue used. Studies with either gemeprost 1 mg or 800 Ag misoprostol given vaginally had a high ( z 95%) success rate. The success rate was in the range of 90% when 400 Ag of misoprostol was given orally. A few pilot studies went even further by giving both drugs on the same day [122,144 ­ 147]. However, this led to a significant decrease in efficacy, which was confirmed by a small RCT showing an efficacy of only 50% after a first dose of 400 Ag of misoprostol given orally the same day as mifepristone [148]. A high percentage of women needed a second dose of misoprostol for incomplete abortion in these studies, as compared to studies with a 2-day interval. 4.3. Evaluation of outcome of medical abortion Summary: Training is required to correctly interpret an ultrasound picture or human chorionic gonadotropin (hCG) level at follow-up. Experienced centers can reduce the frequency of backup curretage for bincomplete abortion.Q The most widely used definition of a successful medical abortion is the avoidance of a surgical intervention [5]. Treatment will result in complete abortion in the vast majority of patients (z 95%) [149]. However, a small percentage will experience incomplete abortion, missed abortion or continuing pregnancy. The following methods are used for evaluating the outcome of treatment at follow-up: ! Visual verification of expulsion following intake of misoprostol

! ! ! ! !

History of clinical events (heavy or continuous bleeding and pain) Gynecological examination hCG in serum measured quantitatively hCG in urine, using a rapid test with a high cut-off value Ultrasound examination

One or several of the abovementioned criteria are used at the follow-up visit [150 ­155]. The large individual variation in the time to expulsion is a disadvantage of using verification of expulsion during the observation period after PG administration (Fig. 7). The gestational age at the beginning of treatment has to be taken into consideration when discussing the diagnostic method used at follow-up. This is because an intrauterine pregnancy becomes difficult or even impossible to diagnose prior to 5 weeks gestation. So far, no standard has been described for the evaluation of successful treatment and various methods are used in clinical practice [149]. Of particular note is that there are no accepted guidelines for interpretation of ultrasound findings at followup. This is an important aspect as some patients present with a thick endometrium even after successful expulsion and may be subjected to unnecessary curettage [156]. Several studies have used serial measurement of hCG to evaluate outcome at follow-up. However, there are large variations in the hCG value at the beginning of the treatment. This makes it difficult to interpret the value at follow-up without knowledge of the initial value [150]. A long duration may be necessary to make sure most patients with successful abortion have a serum hCG below a threshold. Using a urinary test with a cutoff at 1000 mIU/mL at 2 weeks following first-trimester surgical abortion has been

Fig. 7. Expulsion of the gestational sac in medical abortion. Time to expulsion of the sac in 1720 women with successful termination of pregnancy. The women took mifepristone on Day 1 and misoprostol 48 h later. Uncertain means expulsion at some point during 24 h following misoprostol. Unknown means expulsion at some point later than 24 h after misoprostol [modified from N Engl J Med 1998;21:1809­513].

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described (i.e., Duo test, Veda Lab, France) [151]. A urinary test with a cutoff value of 500 mIU/mL is used at the Karolinska University Hospital to verify expulsion at 3 weeks after medical abortion [157]. Most authors have therefore reported the result at followup as percentage of the initial value. One study used a cutoff level at follow-up for successful abortion as 30% of the initial value; in a another study, a cutoff value of 40% of the initial level was recommended [158,159]. A much faster decline has been described: 60 ­70.5% 24 h following misoprostol administration and 99.4% on Day 14 [153,154]. The need for further evaluation had been clearly expressed, but even the current clinical guidelines do not mention a method for verifying expulsion, nor do they give criteria for the interpretation of the findings [70,71,86,151]. The follow-up visit takes place 1­3 weeks following the treatment, depending on the provider. The time interval between treatment and follow-up has an impact on the findings at ultrasound, hCG levels and gynecological examination. The need for another follow-up visit will also be influenced by the time interval. The delay until follow up may also change acceptability of the method. No study has been published so far evaluating these aspects. It could be assumed that women would prefer to know the final diagnosis after a shorter rather than longer interval and prefer fewer follow-up visits. 4.4. Safety Summary: Medical abortion with mifepristone and a suitable PG analogue is a very safe abortion method. Prior to approval of mifepristone, Roussel-Uclaf conducted a comprehensive toxicology program, demonstrating its safety. One and 6 months of treatments in rats and monkeys revealed no true toxicity [33]. The safety for single use in humans was confirmed by a large study of 16,173 cases of medical abortion [17]. Safety in long-term use has been established in several studies for other indications including myoma, endometriosis, breast cancer or meningioma [160 ­ 164]. 4.5. Teratogenicity Summary: There are insufficient data to evaluate the teratogenetic potential of medical abortion. Available evidence suggests some risk. In general terms, it is difficult to evaluate the teratogenetic risk of a substance that is highly abortifaciant. However, studies in rodents using subabortive doses of mifepristone showed no anomaly. Also, no teratogenetic effects were found in studies with rabbits that received mifepristone combined with progesterone to counteract the abortifaciant effect [33]. Another important source of information are records from women who carried their pregnancy to term after a failed medical abortion (Exelgyn, Paris, 2005). A total of 161 cases of continuing pregnancy following failed medical abortion have been reported out of an estimated 1.5 million

procedures performed between 1987 and 2005 in countries where Exelgyn holds marketing authorization. In 58 of these cases, mifepristone was used alone as the women refused to proceed with the treatment. The remaining women took one of the available PGs: misoprostol (65), sulprostone (4), gemeprost (13) or unspecified (21) (Exelgyn 2005) [165]. However, these reports are voluntary and done at the initiative of the treating physician. There is no way to reliably calculate the total number of deliveries after failed medical abortion. In total, 14 cases of malformations were reported out of the reported 161 known deliveries. The teratogenetic risk of misoprostol has been evaluated recently by analyzing animal model evidence, cases reported by the drug manufacturer and the scientific literature [166]. Several studies on this aspect come from Brazil. There, authors found an association between birth defects and in utero exposure to misoprostol, which could be explained by uterine contraction and bleeding induced by misoprostol. Many of the cases with central nervous system anomalies were noted to have some or all of the features of Mfbius syndrome. Mfbius syndrome is a rare condition characterized by the loss of function of the motor cranial nerves and is said to be associated with fetal misoprostol exposure. 4.6. Infection after medical abortion Summary: Very few infections following medical abortion have been reported so far. However, a small number of fatal septic shock following infection with a rare bacteria have been reported from North America since the method was introduced there in 2000. So far, no final conclusion has been reached as to the casual link with details of the treatment. The frequency of infection following aspiration in the first trimester is reported to be as high as 10% but depends strongly on the regional prevalence of sexually transmitted diseases and gestational age at the time of intervention [71]. However, most studies on this topic are from the 1980s. Recently, registered side effects of 56,000 abortions performed between 1980 and 1994 in Denmark were analyzed. Bleeding, infections or reevacuation were recorded in 5% of all cases and did not change over time [167]. In the United Kingdom, prophylactic antibiotic treatment is recommended in order to reduce the frequency of infections [71]. However, this approach to the prevention of infections depends not only on the prevalence but varies also by country. For instance, routine antibiotic prophylactic treatment is given in the United Kingdom, whereas in Scandinavian countries and in China, it is given only on a case-by-case basis with obvious advantages but larger short-term costs. The literature on infection following medical abortion has recently been reviewed and the overall rate was estimated to be 0.92% [168]. An unexpected finding was the high rate of possible infection in the studies from the United Kingdom (10 times higher as compared to studies from other countries). It was suggested that a difference in diagnostic criteria might be the underlying reason, as the

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United Kingdom also reported suspected infection. Excluding the data from the United Kingdom, the overall infection rate fell to 0.28%. Also, no difference was found between different regimens and routes of administration of the PG. Recently, a total of five fatal cases of septicemia during medical abortion have been reported from North America out of an estimated 450,000 cases of medical abortion carried out since approval in 2000 [169 ­171]. In all four cases, as well as in a fifth death in Canada in 2002, a septicemia with the bacteria Clostridium sordellii was the cause of death [171]. No explanation for these fatal events has been found. So far, no causation between septic shock and mifepristone and misoprostol has been shown. Death with the same bacteria have been reported following spontaneous abortion as well as postpartum [172]. Clostridium sordellii is sensitive to common antibiotics such as metronidazole. No such case has been reported from Europe with an estimated number of patients treated with medical abortion of more than 1.5 million for more than 15 years. Recently, another two death cases were reported in association with medical abortion [173]. However, one of these cases has later been confirmed to be unrelated to medical abortion and the one case is still under investigation at the time of submission of this paper [FDA, Mifeprex (mifepristone) Information April 10, 2006 Update. http:// www.fda.gov/cder/drug/infopage/mifepristone]. 4.7. Pain treatment in medical abortion Summary: Avoiding or sufficiently treating pain is of very high importance for the patients. Usual strategies should be applied including prophylactic treatment. Abdominal pain is one of the most common adverse effects of medical abortion [105,109]. Women are much more likely to experience pain during medical abortion than with surgical abortion under general anaesthesia [131]. The pain is most pronounced following the administration of the PG (misoprostol or gemeprost). Consequently, pain remains a decisive factor influencing women's choice of method. Despite the fact that pain experienced during medical abortion causes significant distress, it has been uncommonly studied. There are no studies that directly compare different analgesic regimens or prophylactic medication for pain relief at the time of medical abortion with mifepristone and misoprostol. However, a placebo-controlled, randomized trial evaluated the relative efficacies of ibuprofen or acetaminophen with codeine as prophylaxis in the context of early medical abortion with MTX and misoprostol [174]. The agents were taken as prophylaxis at the time of misoprostol administration, prior to the onset of pain. Severe pain scores were reported by almost a quarter of women, and there were no significant differences in pain scores between treatment groups (placebo, ibuprofen or acetaminophen with codeine). Those women who were given acetaminophen with codeine as prophylaxis reported taking fewer of the same medication in the days following PG administration.

In another nonconcurrent cohort study in early medical abortion, the use of opiate analgesia was shown to be lower when prophylactic acetaminophen was given compared to a control group without prophylactic treatment [175]. 4.7.1. NSAID in medical abortion Summary: The product information contains a recommendation against the use of NSAIDs. However, this is not based on evidence, and several studies suggest that NSAIDs should be an integral part of pain treatment. Management of pain during medical abortion has been hampered by recommendations that NSAIDs should not be given to women, at least until the follow-up visit 8 ­12 days after mifepristone administration. Currently, the United Kingdom data sheet advises, bas they could affect the efficacy of the treatment NSAIDs, including aspirin, should be avoided until pregnancy termination is complete. For termination of pregnancy of up to 63 days of gestation, NSAIDs should not be given at least until the follow-up visit 8­12 days after mifepristone administration.Q This recommendation is based on btheoreticalQ considerations. STo be precise, NSAIDs are effective inhibitors of PG biosynthesis. NSAIDs can significantly prolong the induction-to-abortion interval for abortion methods depending on increased endogenous PG production, such as intrauterine instillation of hypertonic saline or Rivanol [176]. Furthermore, dysmenorrhea, believed to be caused by increased levels of PG, can be treated effectively by NSAIDs [177,178]. So far, there is no evidence that concurrent use of NSAIDs results in a reduction of efficacy of medical abortion. NSAIDs inhibit endogenous PG synthesis and should not influence the effect of exogenous PGs on uterine contractility. A study has shown that indomethacin given together with mifepristone led to a marked reduction in the ability of the decidua to generate PGF2a but had no negative impact on uterine activity [39]. NSAIDs given together with exogenous PG do not appear to influence the effect of PG with regard to uterine contractility or cervical ripening [39,179,180]. NSAIDs also do not affect the efficacy of medical abortion using either MTX or mifepristone followed by misoprostol [181,182]. 4.8. Contraindications Summary: Mifepristone and misoprostol are both very safe drugs and have only a few contraindications. The combination treatment of mifepristone and misoprostol has relatively few contraindications and is well tolerated when used according to the recommendations (SmPC) [50]. The contraindications are the following: ! ! ! ! ! ! ! Allergic reactions to one of the drugs Chronic adrenal failure Severe asthma not controlled by therapy Coagulation disorder Suspected extra uterine pregnancy Porphyria Pregnancy beyond the approved gestational limit

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Precautions: ! ! Long-term systemic corticosteroid therapy Renal failure, liver failure and malnutrition (in the absence of specific studies, the treatment should be avoided in these cases) As a precaution, breastfeeding women should not be treated or discharge the breast milk for 2­ 3 days An intrauterine device in place should be removed before uterine contractions are initiated

! !

Also, the contraindications of the PG analogue used have to be observed, even when the risk of cardiovascular incidences has greatly been reduced with the use of E1 analogues. 4.9. Postabortion bleeding Summary: Uterine bleeding is an inherent aspect of abortion, and the amount is correlated with gestational age. Provisions have to be made for a small percentage of women experiencing very heavy bleeding with the need for emergency curettage. Women undergoing medical abortion observe the blood loss and also perceive it to be heavier than women undergoing surgical abortion with vacuum aspiration [131]. Two studies compared the blood loss with surgical abortion and found significantly more bleeding in medical abortion but no significant change in hemoglobin levels [183,184]. Also, clinical measures showed no significant difference in blood loss between surgical and medical abortion in another large study [185]. Starting oral contraceptive pills immediately after medical abortion had no impact on the total amount of blood loss nor on the efficacy of medical abortion in several studies [186 ­188]. 4.10. Gestational age limits Summary: Medical abortion is effective throughout pregnancy. However, the dosage of the PG needs to be adapted according to the gestational age. Mifepristone is effective as long as it can antagonize progesterone [189]. By definition, it is therefore effective during the entire pregnancy. The first study published with use of mifepristone alone consisted of 11 patients with a pregnancy of up to 8 weeks gestation [6]. The failure rate of 2/11 was attributed by the authors to the high concentration of progesterone in the more advanced pregnancies. Similarly, a later study with mifepristone alone confirmed a negative correlation between high levels of hCG and efficacy [11]. The following studies were then done in gestations below 7 weeks [7,190]. Another study was published using mifepristone alone and included more advanced pregnancies up to 10 weeks of gestation [191]. The findings confirmed the drop in efficacy in pregnancies above 7 weeks of gestation: 80% complete abortion in pregnancies below 7 weeks vs. 33% above 7 weeks of gestation.

The gestational limit of 7 weeks was utilized in the following studies even when a PG analogue was added [14]. This regimen received marketing authorization in France in 1988 [5]. The gestational age limit was confirmed when studies showed a reduction in effectiveness of mifepristone in association with sulprostone or oral misoprostol with increasing gestational age. Also, psychological factors were considered, specifically the stress for the patients of seeing a fetus in case of an advanced pregnancy (a fetus is not visible before 6 1/2 weeks gestation). The psychological aspect has been confirmed by another study that found seeing the fetus was associated with more intrusive events (nightmares, flashbacks, unwanted thoughts related to the experience) [139]. Preliminary studies were also undertaken in the United Kingdom. Drawing on the benefit of the experience in France, the United Kingdom studies increased the limits of experience and investigated the use of mifepristone and gemeprost for termination of pregnancy of up to 56 and then 63 days of gestation [18,192,193]. These studies led to the approval of mifepristone in combination with gemeprost in the United Kingdom for use for termination of pregnancy up to 63 days of gestation in 1991. Using gemeprost did not lead to a loss in efficacy with increasing gestational age. In the following year, mifepristone in association with gemeprost was also approved in Sweden for termination of pregnancy of up to 63 days of gestation. Sweden had previously participated in the WHO studies and had played a crucial role in the development of the method. Therefore, the 63-day gestational age limit of these studies had been the basis of the approval in Sweden. As soon as the efficacy of medical abortion was established for termination of early pregnancy, studies were undertaken at later gestations [194 ­196]. These studies showed that mifepristone followed by repeated doses of PG is also highly effective. Based on these findings, mifepristone was approved for termination of pregnancy beyond the first trimester in France and Sweden in 1992 and in the United Kingdom in 1995. Medical abortion with mifepristone and PG after the first trimester is now recommended in several guidelines and has become the standard of care [70,71]. Interestingly, the interval between 9 and 12 weeks of gestation has only recently been studied with encouraging results, provided that the PG is given repeatedly [197,198]. However, use of mifepristone and PG for termination of pregnancy between 9 and 12 of weeks gestation is not a registered indication in any country, even though it is recommended in the abovementioned guidelines. Medical abortion is also highly effective in late gestation and has even become standard of care in some countries [70,71,157,199,200]. 4.11. Rhesus factor Summary: Insufficient evidence exists so far to judge the need for giving Rhesus (Rh) immunoglobulins to Rhnegative women.

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The introduction of Rh immune globulin for prevention of Rh-isoimmunization was a milestone in obstetrics. It is therefore not surprising that Rh-immunoprophylaxis was applied to all pregnancies, regardless of gestational age. However, gestational age at termination of pregnancy has been declining over the last decades due to advances in abortion technology. The introduction of medical abortion has given women the option of having an abortion at an even earlier gestational age. In a number of cases, no fetal pole is visible on ultrasound, and the question arises: at which gestational age does the risk for Rh-isoimmunization begin? Only few studies have specifically investigated gestations below 12 weeks, and these did not give a precise answer [201]. There is no study on Rh immunization following medical abortion. A few review articles have been published; however, the conclusions differ [202­204]. Further studies are needed to clarify the necessity for Rh-prophylaxis for abortion procedures, especially for medical abortion, in very early gestations.

5. Outlook It seems important to continue the search to find further improvements to the method. Possible future research activities could include the following: ! ! ! ! ! Reduction in bleeding Improving pain treatment Evaluating the need for Rh prophylaxis in a clinical study Allowing women themselves to verify successful abortion using a urinary hCG test Dose-finding studies with slow-release misoprostol and development of a regimen for medical abortion.

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C. Fiala, K. Gemzell-Danielsson / Contraception 74 (2006) 66­86 of a large multicenter trial in the United States. Mifepristone Clinical Trials Group. Arch Fam Med 1998;7:360 ­ 6. Henshaw R, Naji S, Russell I, Templeton A. Psychological responses following medical abortion (using mifepristone and gemeprost) and surgical vacuum aspiration. A patient-centered, partially randomised prospective study. Acta Obstet Gynecol Scand 1994;73:812 ­ 8. Urquhart DR, Templeton AA. Psychiatric morbidity and acceptability following medical and surgical methods of induced abortion. BJOG 1991;98:396 ­ 9. Howie FL, Henshaw RC, Naji SA, Russell IT, Templeton AA. Medical abortion or vacuum aspiration? Two year follow up of a patient preference trial. BJOG 1997;104:829 ­ 33. Slade P, Heke S, Fletcher J, Stewart P. A comparison of medical and surgical termination of pregnancy: choice, emotional impact and satisfaction with care. BJOG 1998;105:1288 ­ 95. Ashok PW, Flett GM, Templeton A. Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study. Am J Obstet Gynecol 2000;183:998 ­ 1002. Heikinheimo O, Suhonen S, Haukkamaa M. One- and 2-day mifepristone­misoprostol intervals are both effective in medical termination of second-trimester pregnancy. Reprod Biomed Online 2004;8:236 ­ 9. Sandstrom O, Brooks L, Schantz A, et al. Interruption of early pregnancy with mifepristone in combination with gemeprost. Acta Obstet Gynecol Scand 1999;78:806 ­ 9. Basu R, Gundlach T, Tasker M. Mifepristone and misoprostol for medical termination of pregnancy: the effectiveness of a flexible regimen. J Fam Plann Reprod Health Care 2003;29:139 ­ 41. Pymar HC, Creinin MD, Schwartz JL. Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception 2001;64:87 ­ 92. Creinin MD, Schwartz JL, Pymar HC, Fink W. Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. BJOG 2001;108:469 ­ 73. Murthy AS, Creinin MD, Harwood B, Schreiber C. A pilot study of mifepristone and misoprostol administered at the same time for abortion up to 49 days gestation. Contraception 2005;71:333 ­ 6. Schreiber CA, Creinin MD, Harwood B, Murthy AS. A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days. Contraception 2005;71:447 ­ 50. Creinin MD, Schwartz JL, Pymar HC, Fink W. Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. BJOG 2001;108:469 ­ 73. Trussell J, Ellertson C. Estimating the efficacy of medical abortion. Contraception 1999;60:119 ­ 35. Thonneau P, Fougeyrollas B, Spira A. Analysis of 369 abortions conducted by mifepristone (RU486) associated with sulprostone in a French family planning center. Fertil Steril 1994;61:627 ­ 31. Paul M, Schaff E, Nichols M. The roles of clinical assessment, human chorionic gonadotropin assays, and ultrasonography in medical abortion practice. Am J Obstet Gynecol 2000; 183(2 Suppl):S34 ­ S43. Bygdeman M, (Gemzell) Danielsson KG, Marions L. Medical termination of early pregnancy: the Swedish experience. J Am Med Womens Assoc 2000;55:195 ­ 6,204. Walker K, Schaff E, Fielding S, Fuller L. Monitoring serum chorionic gonadotropin levels after mifepristone abortion. Contraception 2001;64:271 ­ 3. Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O. The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy. Hum Reprod 2002;17:2315 ­ 9.

[116] Middleton T, Schaff E, Fielding SL, et al. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception 2005;72: 328 ­ 32. [117] Ashok PW, Templeton A. Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br J Obstet Gynaecol 1999;106:706 ­ 10. [118] Ngai SW, Tang OS, Ho PC. Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Hum Reprod 2000;15:2205 ­ 8. [119] Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1993;338:1241 ­ 7. [120] Aubeny E. A two-stage increase in the dose of misoprostol improves the efficacy of medical abortion with mifepristone and prostaglandins. Eur J Contracept Reprod Health Care 2001;6:54 ­ 5. [121] Tang OS, Lee SW, Ho PC. A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone. Hum Reprod 2002;17:2865 ­ 8. [122] Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol 2004; 103:851 ­ 9. [123] Aubeny E. Trends since 1989, in France, of induced abortions by mifepristone (RU486) combined with a prostaglandin analogue [Evolution depuis 1989, en France, des interruptions volontaire de grossesse par mifepristone (RU 486) associee a un analogue de ´ ´ ` prostaglandine]. Contracept Fertil Sex 1997;25:777 ­ 81. [124] Guengant JP, Bangou J, Elul B, Ellertson C. Mifepristone-misoprostol medical abortion: home administration of misoprostol in Guadeloupe. Contraception 1999;60:167 ­ 72. [125] Elul B, Pearlman E, Sorhaindo A, Simonds W, Westhoff C. In-depth interviews with medical abortion clients: thoughts on the method and home administration of misoprostol. J Am Med Womens Assoc 2000;55(3 Suppl):169 ­ 72. [126] Harper C, Ellertson C, Winikoff B. Could American women use mifepristone­misoprostol pills safely with less medical supervision? Contraception 2002;65:133 ­ 42. [127] Fiala C, Winikoff B, Helstrom L, Hellborg M, Gemzell-Danielsson K. Acceptability of home-use of misoprostol in medical abortion. Contraception 2004;70:387 ­ 92. [128] Faucher P, Baunot N, Madelenat P. The efficacy and acceptability of mifepristone medical abortion with home administration misoprostol provided by private providers linked with the hospital: a prospective study of 433 patients [Article in French]. Gynecol Obstet Fertil 2005;33:220 ­ 7. [129] Hamoda H, Critchley HO, Paterson K, Guthrie K, Rodger M, Penney GC. The acceptability of home medical abortion to women in UK settings. BJOG 2005;112:781 ­ 5. [130] Bygdeman M, Danielsson KG. Options for early therapeutic abortion. A comparative review. Drugs 2002;62:2459 ­ 70. [131] Holmgren K. Women's evaluation of three early abortion methods. Acta Obstet Gynecol Scand 1992;71:616 ­ 23. [132] Henshaw RC, Naji SA, Russell IT, Templeton AA. Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment. BMJ 1993;307:714 ­ 7. [133] Safar P, Fiala C. Abortion with mifepristone and misoprostol in Austria -- first experiences [Schwangerschaftsabbruch mit Mife¨ priston und Misoprostol in Osterreich-erste Erfahrungen]. Frauenarzt 2000;41:325 ­ 30. [134] Fielding SL, Edmunds E, Schaff EA. Having an abortion using mifepristone and home misoprostol: a qualitative analysis of women's experiences. Perspect Sex Reprod Health 2002;34:34 ­ 40. [135] Winikoff B, Ellertson C, Elul B, Sivin I. Acceptability and feasibility of early pregnancy termination by mifepristone­misoprostol. Results

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[178] Smith RP. The dynamics of nonsteroidal anti-inflammatory therapy for primary dysmenorrhoea. Obstet Gynecol 1987;70:785 ­ 8. [179] R3destad A, Bygdeman M. Cervical softening with mifepristone (RU 486) after pretreatment with naproxen. A double-blind randomized study. Contraception 1992;45:221 ­ 7. [180] Li CFI, Wong CYG, Chan CPB, Ho PC. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. Contraception 2003;67:101 ­ 5. [181] Creinin MD, Shulman T. Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a regimen for early abortion. Contraception 1997;56:165 ­ 8. [182] Fiala C, Swahn ML, Stephansson O, Gemzell-Danielsson K. The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13­22 weeks gestation. Hum Reprod 2005;20:3072 ­ 7. [183] Chan YF, Ho PC, Ma HK. Blood loss in termination of early pregnancy by vacuum aspiration and by combination of mifepristone and gemeprost. Contraception 1993;47:85 ­ 95. [184] Prasad RN, Choolani M, Roy A, Ratnam SS. Blood loss in termination of early pregnancy with mifepristone and gemeprost. Aust N Z J Obstet Gynaecol 1995;35:329 ­ 31. [185] Harper C, Winikoff B, Ellertson C, Coyaji K. Blood loss with mifepristone­misoprostol abortion: measures from a trial in China, Cuba and India. Int J Gynaecol Obstet 1998;63:39 ­ 49. [186] Martin CW, Brown AH, Baird DT. A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary. Contraception 1998;58:99 ­ 103. [187] Tang OS, Gao PP, Cheng L, Lee SW, Ho PC. A randomized doubleblind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum Reprod 1999;14:722 ­ 5. [188] Tang OS, Xu J, Cheng L, Lee SW, Ho PC. The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial. Hum Reprod 2002;17:99 ­ 102. [189] Bygdeman M, Gemzell K, Gottlieb C, Swahn ML. Uterine contractility and interaction between prostaglandins and antiprogestins. Clinical implications. Ann N Y Acad Sci 1991;626:561 ­ 7. [190] Baulieu EE, Ulmann A. Steroidal antihormones: the antiprogesterone activity of RU486 and its contragestive and other applications. Bull Acad Natl Med 1985;169:1191 ­ 200. [191] Haspels AA. Interruption of early pregnancy by an anti-progestational compound, RU 486. Eur J Obstet Gynecol Reprod Biol 1985;20:169 ­ 75. [192] Cameron IT, Michie AF, Baird DT. Therapeutic abortion in early pregnancy with antiprogestogen RU 486 alone or in combination with a prostaglandin analogue (gemeprost). Contraception 1986; 34:459 ­ 68. [193] Rodger MW, Baird DT. Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. Lancet 1987;2:1415 ­ 8. [194] Hill NC, Selinger M, Ferguson J, Lopez Bernal A, Mackenzie IZ. The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester. Br J Obstet Gynaecol 1990;97:487 ­ 92. [195] Rodger MW, Baird DT. Pretreatment with mifepristone (RU 486) reduces interval between prostaglandin administration and expulsion in second trimester abortion. BJOG 1990;97:41 ­ 5. [196] Urquhart DR, Templeton AA. The use of mifepristone prior to prostaglandin-induced mid-trimester abortion. Hum Reprod 1990; 5:883 ­ 6. [197] Ashok PW, Kidd A, Flett GM, Fitzmaurice A, Graham W, Templeton A. A randomized comparison of medical abortion and surgical vacuum aspiration at 10­13 weeks gestation. Hum Reprod 2002; 17:92 ­ 8.

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C. Fiala, K. Gemzell-Danielsson / Contraception 74 (2006) 66­86 [201] Thong KJ, Norman JE, Baird DT. Changes in the concentration of afetoprotein and placental hormones following two methods of medical abortion in early pregnancy. BJOG 1993;100:1111 ­ 4. [202] Jabara S, Barnhart K. Is Rh immune globulin needed in early firsttrimester abortion? A review. Am J Obstet Gynecol 2003;188: 623 ­ 7. [203] Fiala C, Fux M, Gemzell Danielsson K. Rh-prophylaxis in early abortion. Acta Obstet Gynecol Scand 2003;82:892 ­ 903. [204] Jones ML, Wray J, Wight J, et al. A review of the clinical effectiveness of routine antenatal anti-D prophylaxis for rhesusnegative women who are pregnant. BJOG 2004;111:892 ­ 902.

[198] Hamoda H, Ashok PW, Flett GM, Templeton A. Medical abortion at 9­13 weeks' gestation: a review of 1076 consecutive cases. Contraception 2005;71:327 ­ 32. [199] el-Refaey H, Hinshaw K, Templeton A. The abortifacient effect of misoprostol in the second trimester. A randomized comparison with gemeprost in patients pre-treated with mifepristone (RU 486). Hum Reprod 1993;8:1744 ­ 6. [200] Gemzell-Danielsson K, Ostlund E. Termination of second trimester pregnancy with mifepristone and gemeprost. The clinical experience of 197 consecutive cases. Acta Obstet Gynecol Scand 2000; 79:702 ­ 6.

Interventi

RU 486: una proposta indecente?

di Silvio Viale*

L'aborto dimenticato

La proposta di introdurre in Italia il mifepristone, la «pillola abortiva» più nota come RU 486, con una sperimentazione clinica di fase II, presso l'Ospedale S. Anna di Torino, ha suscitato prevedibili polemiche, ma anche molto interesse. Polemiche da parte del fronte antiabortista, che si oppone alla RU 486 per principio, in «difesa della vita». Interesse da parte di chi continua a occuparsi di aborti, nonostante l'ignavia della sanità pubblica e del mondo politico. Purtroppo il dibattito non si è sviluppato su un piano scientifico-sanitario, a causa dell'oblio che è calato sull'argomento «aborto» per vent'anni, con la conseguenza che da ambo le parti prevalgono toni, argomentazioni e propaganda da «anni settanta», gli unici a disposizione dopo anni di autocensura. Così accade che si continui a confondere con insistenza la «pillola del giorno dopo», cioè la contraccezione post-coitale, con la «pillola abortiva». Per evitare tale confusione, negli Stati Uniti si è adottata la definizione di «pillola del mese dopo» per la RU 486. Vi è anche una battaglia terminologica, dispregiativa. Agli antiabortisti non piace la definizione di «aborto medico», adottato dalla letteratura internazionale, in alternativa a quella di «aborto chirurgico». Essi preferiscono chiamarlo «aborto chimico», ma non «aborto farmacologico», che sarebbe la definizione più corretta, visto che si tratta di un aborto indotto con farmaci. Tra la gente invece è sempre più popolare come «l'aborto con la pillola». Questo tentativo di demonizzare il farmaco «cattivo» è incomprensibile, poiché la RU 486 e le varie prostaglandine, oltre che per gli aborti medici del primo e del secondo trimestre, sono utilizzati anche per il trattamento degli aborti spontanei, per preparare quelli chirurgici, per indurre i travagli di feti vivi o morti nel terzo trimestre e in altri campi della medicina. In Italia la Commissione unica del farmaco (CUF) ha già auto* Ospedale S. Anna, Torino.

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rizzato il mifepristone per il trattamento della sindrome di Cushing di origine paraneoplastica,1 un'indicazione non registrata in alcun paese. Nella clinica dell'aborto metodi medici e metodi chirurgici sono sovrapponibili (fig. 1) e la scelta dipende da indicazioni mediche, da abitudini locali e dai desideri della donna, per cui si comprende come sia quasi impossibile trovare argomentazioni logiche contro una particolare modalità di aborto, peraltro quella meno invasiva. Non a caso, i pochi ginecologi, che ci si sono cimentati, si sono limitati a ribadire la propria contrarietà ideologica all'aborto. Una conseguenza dell'assenza di discussione scientifica sull'aborto è il ricorso esclusivo all'intervento chirurgico per gli oltre 70.000 aborti spontanei, che vengono denunciati ogni anno in Italia2 e che in parte potrebbero beneficiare dei metodi medici.

Figura 1. Metodi per l'aborto a differenti epoche di gestazione (settimane dall'ultima mestruazione). About abortion care, Royal College of Obstetricians and Gynaecologists, Maggio 2001.

Vi è un certo timore politico ad affrontare la discussione scientifica, che nasce anche dal desiderio di evitare il confronto con gli aspetti dialettici e pluralistici della bioetica, che è probabilmente alla base della richiesta di rimuovere dallo studio sperimentale del S. Anna la parte sull'aborto interno e sull'uovo anembrionato, suggerendo di limitare lo studio al solo aborto volontario.

1. Inserimento del medicinale Mifepristone nell'elenco dei medicinali erogabili a totale carico del Servizio sanitario nazionale ai sensi dell'art. 1, comma 4, del decreto-legge 21 ottobre 1996, n. 536, convertito dalla legge 23 dicembre 1996, n. 648, per il trattamento della sindrome di Cushing di origine paraneoplastica. Ministro della Sanità 15 gennaio 1999, Gazzetta Ufficiale n. 51 del 3 marzo 1999, p. 24. 2. ISTAT, Annuario statistico italiano 2002, ottobre 2002.

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Interventi

Tornando alle polemiche, in questi due anni si è oscillato da un iniziale goffo tentativo di sostenere che l'aborto sarebbe stato più facile alla tesi opposta di una presunta maggiore pericolosità per la donna, per approdare infine a una criptica e curiosa interpretazione legale della 194, che è attualmente il pretesto con il quale non si è ancora conclusa l'ispezione nei confronti dell'Ospedale S. Anna, voluta dal ministro della Salute Girolamo Sirchia. Ovviamente il tentativo del ministro di ritardare l'introduzione della RU 486 in Italia, come l'opposizione dei gruppi cattolici, non è collegabile a un obiettivo progettuale di ridurre gli aborti nel nostro paese, che renderebbe comprensibile una certa forma di guerriglia, soprattutto nel caso di un aumento di «bambini uccisi». Il ministro Sirchia non può non conoscere la quindicinale esperienza europea3,4 e, quindi, sa bene come l'aborto medico riguardi solo le donne, che hanno già deciso di interrompere la gravidanza, e non influisca sulla decisione di abortire (fig. 2). In altre parole, non vi è nessuna donna che decide di abortire a cau-

25 20 15 10 5 0 1988 1989 1990 1991 1992 1993 1994 1995

Medical abortion approved Svezia Inghilterra e Galles Francia Italia Figura 2. Tendenza degli aborti dopo l'introduzione della RU 486 3. R. K. Jones, S. K. Henshaw, «Mifepristone for early medical abortion: experiences in France, Great Britain and Sweden», Persp Ses Rep Health, 2002, 34, pp. 154-161. 4. S. K. Henshaw, S. Singh, T. Haas, «Recent trends in abortion rates worldwide», Int plan fam persp, 1999, 25, pp. 44-48.

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sa della disponibilità del metodo medico, ma che non lo farebbe con il metodo chirurgico, o viceversa. Lo conferma anche la ventennale esperienza dei Centri di aiuto alla vita (CAV), che cercano di agire sulle motivazioni e sulle indecisioni delle donne, ma non sulla paura dell'intervento chirurgico (I trimestre) o di quello medico (II trimestre), tant'è che, nonostante si tratti di donne sensibili ai temi della vita dell'embrione, una buona parte di loro decide ugualmente di abortire.5 Inoltre, dal punto di vista dell'embrione, è difficile sostenere che continuare a essere «fatto a pezzi» dall'aborto chirurgico sia preferibile all'espulsione «chimica» dell'aborto medico, sebbene per quest'ultimo vengano usati termini come «gasato», «avvelenato» o «morire di fame», preferendo lasciare in un limbo descrittivo l'azione della pompa dell'isterosuttore e degli strumenti chirurgici. L'opposizione alla RU 486 è in realtà solo politica e rappresenta il desiderio, più o meno conscio, di una rivincita su quel fronte, che 25 anni fa legalizzò l'aborto e, tre anni dopo, vinse la consultazione referendaria. Si tratta di un rigurgito assolutista e irrazionale, poiché proprio la legalizzazione ha consentito di ridurre il numero di aborti e di attuare quella prevenzione, compresa quella dei movimenti antiabortisti, che è tuttora assente nei paesi ove domina l'aborto clandestino. La prova più evidente viene dalla cultura abortista, pre 194, delle donne immigrate, provenienti dai paesi dell'Asia, dell'Africa e dell'America latina dove l'aborto è vietato, per volere delle religioni islamica e cattolica (fig. 3). Un'altra prova viene dall'altissimo tasso di aborto delle donne rumene, vittime di un ventennio di divieti di tipo vaticano su aborto e contraccezione, imposto da Ceaucescu. Se il ministro Sirchia fosse davvero interessato a ridurre gli aborti in Italia, piuttosto che opporsi alla RU 486, dovrebbe impegnarsi maggiormente nella prevenzione, sfruttare i successi della legalizzazione (in vent'anni gli aborti legali si sono dimezzati e quelli clandestini si sono ridotti a meno di un quinto) ottimizzando gli spazi di intervento che ha permesso. Non vi è infatti più alcuna ragione che possa contrapporsi a forme di prevenzione e di consultazione, ideologicamente orientate, non coercitive, anche da parte di movimenti antiabortisti, purché non si tratti delle forche caudine invocate da alcuni movimenti cattolici. Su fronte opposto, occorre ricordare che non fu una battaglia facile quella che iniziò nel settembre del 1973, con la fondazione del CISA (Centro italiano sterilizzazione e aborti), poiché esisteva molta diffidenza politica e tanta indifferenza, per una questione considerata secondaria, che

5. Convegno nazionale CAV, Torino 15-16 novembre 2002. Materiali preparatori. F. Garelli «Quali esperienze trasferibili?».

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Figura 3. Nei paesi colorati in scuro l'aborto è vietato o fortemente limitato.

implicava uno scontro con le gerarchie e le organizzazioni cattoliche. Il referendum sul divorzio (1974), la prospettiva di quello sull'aborto (1975), la disobbedienza civile (1975), la sentenza della Corte Costituzionale sull'aborto terapeutico (1975) e prima ancora quella sui contraccettivi (1971) furono formidabili sollecitazioni della società civile alle forze politiche. Quella stessa diffidenza ricompare oggi di fronte alla proposta di utilizzare un farmaco riconosciuto dalla farmacopea europea, la cui registrazione in Italia dovrebbe essere un atto dovuto per le procedure di «mutuo riconoscimento». Sia a destra che a sinistra, la principale preoccupazione sembra essere quella di non scontentare gli alleati cattolici, mostrando una sudditanza psicologica che è all'origine di quel persistente disimpegno, che ha contribuito a confinare il più diffuso intervento chirurgico femminile (superato solo negli ultimi anni dal taglio cesareo) ai margini dell'attività sanitaria dei nostri ospedali e degli interessi dei responsabili della sanità. Occorre essere sinceri. L'aborto volontario è un aspetto non gradevole, né gratificante, della vita professionale, anche per la sua simbologia inconscia, indipendentemente da ogni convinzione sull'origine della vita. L'aborto non è generalmente considerato un valore positivo, nemmeno dalle donne che vi ricorrono, e non è quasi mai una strategia progettuale per nessuno. E' piuttosto una necessita imprevista, di cui spesso ci si sentiva immuni fino al giorno della positività al test di gravidanza e alla prospettiva concreta di dovere affrontare le sue conseguenze personali e sociali di una gravidanza; per cui la donna che decide di affrontare l'aborto, ha spesso

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la sensazione di trovarsi sola e giudicata con sufficienza, anche quando l'ambiente non le è ostile. Paradossalmente, sono i successi della prevenzione e il diffondersi della contraccezione che renderanno l'aborto sempre più la prerogativa di una minoranza, rimedio a un fallimento contraccettivo spostato negli anni come tutta la vita riproduttiva, o l'espressione di una marginalità sociale e culturale. La netta riduzione degli aborti tra le donne sposate con figli dimostra che per le donne italiane l'aborto non è più un metodo per il controllo delle nascite, ma la riduzione da due terzi a un terzo del numero di donne, che avranno un aborto volontario nell'arco della propria vita riproduttiva, ha accentuato una certa illusione di immunità collettiva, soprattutto nelle giovani, che ha iniziato a minare la memoria storica delle donne e, forse, anche la solidarietà. Il rischio concreto è che le donne che abortiscono siano sempre più una minoranza, potenzialmente sempre più criminalizzata. E' un paradosso dei successi della legalizzazione, che rende doppiamente colpevole la diserzione del fronte laico e dei movimenti femminili sui temi dell'aborto, mentre viceversa ci sarebbe stato bisogno di una maggiore presenza politica e culturale. Colpevoli nei confronti delle donne, destinate a essere sempre più sole, in balia di piccoli e grandi soprusi.

Figura 4. Interruzioni volontarie di gravidanza per classi di età. Anni 1980-2000 (tassi per 1.000 donne) Istat, Annuario statistico italiano 2002.

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Colpevoli nei confronti degli operatori, ai quali si sono sempre negate le necessarie gratificazioni professionali, economiche e di carriera. La conseguenza è il dilagare di un'obiezione di coscienza di comodo, fatta perlopiù per evitare un lavoro in più o per occuparsi di questioni più appaganti, con moltissimi colleghi che si sono stufati di fare aborti in un sistema dove, piuttosto che la lealtà alla legge, è l'obiezione che viene premiata. La 194 presuppone infatti una complicità ideologica e non riconosce il ruolo professionale di chi garantisce gli interventi per deontologia, indipendentemente dalle proprie convinzioni personali. Se in politica si può essere personalmente contrari all'aborto, ma favorevoli alla legge e al diritto della donna di scegliere se proseguire una gravidanza, per un medico questo significa garantire una prestazione professionale, anche indipendentemente dalla propria opinione personale. Sotto questo aspetto, l'attuazione della 194 non ha meccanismi di garanzia, per cui i medici che fanno aborti sono di fatto dei volontari. Ma non è questa la sede per discutere i limiti della 194, troppo spesso difesa solo da una facile retorica difensiva da palazzo del fronte pro choice, limitandomi a sottolineare come l'impoverimento del dibattito, l'abbandono delle donne, il crescente disagio dei medici non obiettori e la farisaica contagiosa preponderanza di antiabortisti tra i politici, siano principalmente da imputare all'indolenza di coloro che dovrebbero tutelare e promuovere i valori di quella che rimane una battaglia laica di libertà, centrata sul pluralismo etico del diritto di scelta. E' una responsabilità da imputare, prima di tutto, ai movimenti delle donne, che in Italia non hanno voluto mantenere una rete di sostegno e che sacrificano alle contingenti ragioni politiche i temi dell'aborto e della contraccezione, in stridente contrasto con la frenetica attività dei movimenti antiabortisti. Una anomalia italiana, poiché in tutto il mondo la battaglia per la RU 486 è condotta soprattutto dai movimenti femministi e dai gruppi di pianificazioni familiare, mentre in Italia fino allo scoppiare delle polemiche la RU 486 era totalmente assente dai siti web italiani delle donne, della politica e dei medici). A parziale giustificazione si deve osservare come la statalizzazione dell'aborto, imposta 25 anni fa per le opposte esigenze di controllo dei cattolici e della sinistra, abbia contribuito a impedire l'emergere e il consolidarsi di quelle iniziative indipendenti, che si sono viceversa sviluppate in altri paesi e che avrebbero potuto sopperire al cedimento della politica. E' purtroppo tragicamente sintomatico che nessuna delle grandi organizzazioni internazionali di pianificazione familiare abbia una presenza significativa in Italia. Tutto ciò è stato duramente pagato nel recente dibattito parlamentare

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sul disegno di legge governativo sulla fecondazione assistita, per cui si comprende come la RU 486 possa rappresentare l'inizio di una inversione di tendenza. Discutere di RU 486 e di aborto significa ridare dignità politica e sociale ai temi della riproduzione e riconoscere finalmente dignità professionale agli operatori dell'aborto. E' un'importanza che hanno cominciato a capire in molti. Oltre ai Radicali, ci sono state le prese di posizione delle donne DS e delle donne socialiste, ma sono emblematici anche i silenzi di Margherita e Forza Italia nei confronti degli schiamazzi di AN, UDC e Popolari. La regioni Toscana e Umbria hanno preso l'iniziativa. La regione Piemonte continua nella scelta di rispettare l'autonomia sanitaria dei medici del S. Anna e del Comitato etico. Ai medici del S. Anna è giunta la disponibilità di colleghi di quasi tutti gli ospedali del Piemonte e manifestazioni di interesse da molte altre regioni. Il mondo sanitario sembra lentamente risvegliarsi a dieci anni dalla isolata partecipazione della III Clinica ostetrica di Milano a uno studio multicentrico dell'Organizzazione mondiale della sanità.6 Al 78° Congresso nazionale della Società italiana di ostetricia e ginecologia (SIGO) è stata presentata una relazione su «Nuovi metodi per l'aborto medico (mifeprisone e misoprostol)», 7 e quest'anno al 79° Congresso di Catania si discuterà di «Aborto del primo trimestre: induzione farmacologia o trattamento chirurgico?». 8 Non è molto, se lo confrontiamo al dinamismo internazionale. Le linee guida della Federazione internazionale di ostetricia e ginecologia (FIGO) invitano a garantire sia l'aborto medico che chirurgico9 e quest'anno in Cile, in uno dei pochi paesi dove le donne finiscono ancora in galera per l'aborto, al congresso mondiale ci saranno due sessioni sull'aborto medico,10,11 coordinate significativamente dal Comitato per i diritti sessuali e riproduttivi delle donne. Con questo intervento si vogliono fornire gli elementi per un approfon6. WHO, «Pregnancy termination with mifepristone and gemeprost: a multicenter comparaison betwen repeated doses and a eingle dose of mifepristone», Fert Steril, 1991, 56, pp. 3234. 7. M. Campogrande, M. Massobrio, S. Viale, M. Pagliano, F. Maschera, Ospedale S. Anna di Torino, «Nuovi metodi per l'aborto medico (mifepristone e misoprostol)», Relazione al 78° Congresso SIGO. Non agli atti. 8. Dalla fecondazione alla nascita. 79° Congresso nazionale SIGO. 44° Congresso AOGOI. 11° Congresso AGUI. Catania 12-15 ottobre 2003 www.sigo2003.it. 9. FIGO, «Committee for Ethical Aspect of Human Reproduction and Women's Health. Ethical guidelines regarding induced abortion for non-medical resons (Cairo, March 1998)», Int J Gynecol Obstet, 64(3). 10. Safe termination of pregnancy within the law: medical methods. Committee for Women's Sexual and Reproductive Rights. Thursday, november 6, 2003, h 15.00-18.15. World congress of gynecology and obstetrics. Santiago, Chile. General assembly. www.figo2003.com.

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dimento, per contribuire alla riflessione, nella convinzione, che gli ostacoli all'introduzione del mifepristone siano la conseguenza di un pregiudizio scientifico, destinato certamente a cadere, e di una ingiustificata codardia politica, forse più difficile da superare. Ma è solo una questione di tempo.

Perché una sperimentazione

In un corsivo pubblicato su Medicina e morale, la rivista dell'Università cattolica di Roma, dopo avere constatato che la pillola abortiva «è stata oggetto di una lunga e policentrica sperimentazione», si sbotta in un «non si comprende l'esigenza di aggiungerne un'altra».12 In un altro intervento sul medesimo numero si esprimono dubbi «sull'utilità di un'ulteriore sperimentazione, che sembra essere una escamotage per introdurre la pratica dell'aborto medico nel nostro paese».13 Sono d'accordo. Il ragionamento è fondato, perché non vi è più alcun bisogno di dimostrare l'efficacia e la sicurezza del mifepristone, se per sperimentazione si intende la fase preliminare all'introduzione di un farmaco, non essendoci più alcun ostacolo scientifico all'inserimento del mifepristone (Mifegyne) nella farmacopea nazionale. Infatti, se venisse chiesta la procedura di mutuo riconoscimento, la registrazione del prodotto in Italia sarebbe un puro fatto tecnico, ma la Exelgyn non lo vuole fare perché sostiene di non aver trovato alcuna ditta italiana disposta a distribuire il farmaco. Così il farmaco viene negato alle donne italiane, non per motivi medici, non per motivi sanitari, ma per motivi politici. Vi sono comunque alcuni aspetti legati al metodo medico, che indicano quindi la necessità di una sperimentazione: il farmaco non è in commercio, vi è l'associazione con una prostaglandina, l'uso della prostaglandina ha un'indicazione diversa da quella registrata e la sua via di somministrazione è diversa da quella di registrazione. Come si dovrebbe sapere, l'attività di sperimentazione clinica dovrebbe riguardare i casi di medicinali non formalmente ammessi alla vendita al pubblico, o ammessi alla vendita al pubblico, ma il cui impiego avvenga in difformità rispetto alle indicazioni, alla via di somministrazione, o alla

11. New guidelines on the termination of pregnancy. Committee for Women's Sexual and Reproductive Rights, IPAS and Engender Health. Fryday, november 7, 2003, 9.00-10.30. World congress of gynecology and obstetrics. Santiago, Chile. www.figo2003.com. 12. A. Fiori, E. Sgreccia, «L'aborto medico ed i suoi problemi», Medicina e morale, 2002, 6, pp. 1015-1017. 13. M. L. Di Pietro, M. Casini, «Il mifepristone», Medicina e morale, 2002, 6, pp. 1047-1079.

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posologia stabilite dal decreto di registrazione.14 Se un prodotto è già sul mercato, gli studi clinici miranti a indagare, per esempio, nuove indicazioni, nuove vie di somministrazione o nuove associazioni, vanno considerati come studi su nuovi prodotti medicinali, cioè non ancora autorizzati all'immissione in commercio e quindi devono essere di fasi precedenti alla IV.15 (Solo in campo oncologico, il medico è pienamente autorizzato a somministrare in singoli casi, un medicinale per una indicazione o per una via di somministrazione o una modalità di somministrazione o di utilizzazione diversa da quella autorizzata, qualora ritenga, in base ad atti documentabili, che il paziente non possa essere utilmente trattato con medicinali gia approvati, e purché tale impiego sia noto e conforme a lavori apparsi su pubblicazioni scientifiche accreditate in campo internazionale.16 Nella pratica medica è però così comune l'uso di farmaci per indicazioni, o per vie di somministrazione, diverse da quelle registrate,17 che può sembrare superfluo e stravagante quello che, invece, è racchiuso nelle norme. A dire il vero si sarebbe potuto procedere senza la sperimentazione. Una via avrebbe potuto essere quella di un provvedimento di urgenza del giudice civile, come è già accaduto per altre questioni sanitarie. Un'altra via possibile sarebbe stata quella che permette di acquisire farmaci registrati all'estero, qualora non esistano valide alternative terapeutiche, persuadendo i responsabili della struttura sanitaria a iniziare le procedure per l'acquisizione del farmaco all'estero, tramite il visto di competenza del ministero.18 Con una forzatura è anche ipotizzabile un uso diretto da parte di un ginecologo ospedaliero, giunto in possesso del farmaco, nel rispetto delle procedure previste dalla 194; difficilmente sarebbe condannato per la somministrazione, in scienza e coscienza, di un farmaco registrato in un paese dell'Unione europea, previa acquisizione del consenso informato, e probabilmente sarebbe difeso dall'Ordine dei medici e dai sindacati di categoria. In tutti questi casi potrebbe valere un principio di uguaglianza sanitaria dei cittadini europei. Per quanto riguarda la prostaglandina in questione, il misoprostol (Cyto14. «Regolamento per la costituzione, l'organizzazione ed il funzionamento dei Comitati etici nonché norme in materia di sperimentazione clinica», DGR 16 novembre 2001. BUR 47, 21.11.2001. 15. Aggiornamento della circolare ministeriale n. 8 del 10 luglio 1997 relativa alla sperimentazione clinica dei medicinali. Circolare ministeriale n. 15 del 5 ottobre 2000. 16. Disposizioni urgenti in materia di sperimentazioni cliniche in campo oncologico e altre misure in materia sanitaria. DL 17 febbraio 1998, n. 23. (Decreto Di Bella). 17. Per esempio l'uso in gravidanza della nifedipina, un antipertensivo controindicato in gravidanza accertata o presunta. 18. DL 21 ottobre 1996, n. 536. «Misure per il contenimento della spesa farmaceutica e la rideterminazione del tetto di spesa per l'anno 1996». Legge 23 dicembre 1996, n. 648, GU n. 300.

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tec® e Misodex®), tutti gli ostacoli cadrebbero se si adottasse il gemeprost (Cervidil®), una prostaglandina routinariamente utilizzata per indurre aborti in Italia e, in molti paesi europei, in associazione proprio con il mifepristone. Infine, in attesa di potere avere il farmaco migliore, si sarebbe potuto iniziare la pratica dell'aborto medico nel primo trimestre con i farmaci abortivi disponibili in Italia (misoprostol, gemeprost, dinoprostone, metotrexate e tamoxifene) per indurre legalmente gli aborti volontari (Fig. 5).

Figura 5. I farmaci più utilizzati per l'aborto.

Con queste osservazioni si vuole rilevare come la legislazione italiana permetta certamente altre vie a un medico che agisce in scienza e coscienza, con il consenso informato della paziente e il sostegno della letteratura internazionale, ma che la via della sperimentazione è forse da considerare quella più corretta, e più prudente, per aprire la strada

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all'uso clinico del mifepristone, in assenza dell'iniziativa di registrazione da parte della ditta produttrice. Non si tratta quindi di una escamotage, ma di un intento dichiarato, tant'è che in una delle sue ultime comunicazioni, il Comitato etico osserva come «si lascia trasparire che l'attuale sperimentazione è, in sostanza, il cavallo di Troia che dovrà finalmente portare l'aborto farmacologico nel nostro paese». Ma non è forse questo lo scopo di ogni sperimentazione clinica? Quello appunto di verificare nuovi metodi al fine della loro introduzione nella pratica clinica? In ogni caso non si è mai trattato di una sperimentazione fittizia, nemmeno nella sua ultima «ridotta» quarta versione, e lo studio sarebbe considerato sperimentale anche nei paesi che praticano l'aborto medico da più tempo, come Francia, Regno Unito o Svezia. Con esso si indaga un dosaggio del mifepristone (200 mcg) diverso da quello di registrazione (600 mcg) e si studia una indicazione del misoprostol diversa da quella per cui è stato registrato dall'azienda produttrice.

L'inizio della storia

Nel 1999 la Exelgyn, l'azienda francese che nel 1997 ha avuto il brevetto dalla Hochst, ha ottenuto dall'agenzia europea per i farmaci di potere commercializzare il Mifegyne in otto paesi della Unione europea (Austria, Belgio, Danimarca, Finlandia, Germania, Grecia, Spagna, Olanda), dopo che la Hochst per anni aveva bloccato la diffusione del farmaco, con l'eccezione di Francia, Regno Unito e Svezia. Nello stesso anno il farmaco veniva registrato nel Lussemburgo. In quella occasione la Exelgyn decise di non chiedere la procedura del mutuo riconoscimento per il Portogallo, per l'Irlanda e per l'Italia. Se sono comprensibili le motivazioni per l'Irlanda, dove l'aborto è vietato, o per il Portogallo, dove è fortemente limitato, non si capisce il perché dell'esclusione dell'Italia, dove l'aborto è legale dal 1978. Cronache giornalistiche attribuiscono questa decisione all'esistenza di un impedimento di legge, ma la vera motivazione è certamente politica. Non si sa peraltro quale siano stati i consulenti della Exelgyn, che le abbiano consigliato di non procedere la registrazione con un governo di centrosinistra, anche se con un popolare al Ministero della sanità. Con un sorprendente sincronismo, nella stessa primavera del 1999 la pillola abortiva veniva però autorizzata da un decreto del ministro Rosy Bindi (parere CUF) per il trattamento di una patologia endocrina. Tra il 1999 e il 2000 il Mifegyne veniva registrato in molti paesi, tra i

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quali Svizzera, Russia, Norvegia, Canada, Isreale, Tunisia, Nuova Zelanda, Sud Africa, Taiwan eccetera. Il 28 settembre 2000 la Food and Drug Administration (FDA) autorizzava il farmaco negli Stati Uniti, dove è distribuito con il nome di Mifeprex® dai laboratori Danco, su brevetto di un'associazione non-profit, la Population Council. In Italia, nell'autunno del 2000 la Angelini completava la pratica per il mutuo riconoscimento di un preparato per la contraccezione di emergenza, il Norlevo®. Fino ad allora nessuna delle aziende che distribuisce la «pillola del giorno dopo» in altri paesi europei aveva osato chiedere la registrazione in Italia. Nonostante da sempre si utilizzassero altri preparati, registrati per altre indicazioni, per lo stesso scopo, scoppiava la polemica da parte dei movimenti cattolici con tanto di promesse di boicottaggio, che non sono mai decollate, così che pochi mesi dopo l'esempio è seguito dalla Shering, con la registrazione del Levonelle®. La registrazione della «pillola del giorno dopo», considerata abortiva dal mondo cattolico alla pari della pillola abortiva, dimostrava come fossero false le preoccupazioni per la registrazione della RU 486, e proprio la reazione smisurata, incapace di distinguere, del fronte antiabortista rendeva scientificamente e politicamente intollerabile il continuare a negare l'uso del mifepristone alle donne italiane. Questa breve cronistoria illustra il contesto in cui è maturata la decisione di rompere gli indugi e che ha condotto alla sperimentazione del S. Anna, il cui primo atto è stato la presentazione, il 6 novembre del 2000, di una interpellanza al Consiglio comunale di Torino,19 che è ripresa in Consiglio regionale del Piemonte dai Radicali.20 Con essa si chiedeva se esistesse qualche direttiva regionale o nazionale che impedisse l'aborto farmacologico. Nella risposta l'assessore alla Sanità della regione Piemonte osservava che la legge non definisce i metodi di intervento, ma «demanda ai medici, secondo scienza e coscienza, la scelta delle modalità di interruzione della gravidanza», aggiungendo che «le modalità di interruzione della gravidanza sono stabilite, nelle varie strutture, a seconda dei casi, in base alle valutazioni del personale medico, nell'esercizio della libertà di scelta terapeutica, che rimane una inalienabile prerogativa del medico».20 Del resto il dimenticato articolo 15 della legge 194 continua a prevedere «l'aggiornamento [...] sull'uso delle tecniche più moderne, più rispettose dell'integrità fisica e psichica della donna e meno rischiose per l'interruzione della gravidanza». E'

19. Contraccezione postcoitale e aborto farmacologico. Interpellanza presentata del consigliere Silvio Viale in data 6 novembre 2000. N. 2000/09843. 20. Contraccezione postcoitale e aborto farmacologico. Interrogazione n. 341 presentata il 6 novembre 2000 dai consiglieri Carmelo Palma e Bruno Mellano. Regione Piemonte, risposta dell'assessore alla Sanità. Prot. n. 449/jc del 12 dicembre 2000.

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evidente che nel 1978 la legge non potesse escludere che l'evoluzione della medicina avrebbe potuto portare a nuove modalità di intervento, sconosciute a quel tempo. Così, a dicembre del 2000 fu annunciata l'intenzione di richiedere l'aborto farmacologico al S. Anna e la richiesta fu presentata alla Direzione sanitaria dell'Ospedale il 29 gennaio 200121 e illustrata il 31 gennaio in una conferenza stampa, che fu però snobbata dalla stampa locale e nazionale.

La decisione

Con la richiesta del 29 gennaio 2001 non si chiedeva affatto la sperimentazione, ma si proponeva di attivare un servizio per l'aborto fino a 49 giorni con tre protocolli farmacologici: mifepristone-misoprostol, metotrexate-misoprostol e solo misoprostol. Si trattava di utilizzare da subito il metotrexate e misoprostol, farmaci disponibili, e di avviare la pratica per acquisire il mifepristone come previsto dal decreto ministeriale 7 settembre 2000. La proposta non era per niente velleitaria poiché partiva dal fatto che il metotrexate è utilizzato da tempo, anche al S. Anna, per interrompere le gravidanze extrauterine con il medesimo dosaggio.22,23 Inoltre, sull'impiego del metotrexate nell'aborto medico, esiste un'ampia letteratura internazionale che lo propone come una valida alternativa al mifepristone.24-34 Peraltro, il metotrexate è stato a lungo utilizzato negli Stati Uniti, quando non vi era la disponibilità del mifepristone.

21. Aborto medico al S. Anna. Richiesta di attivazione del servizio in applicazione della legge 194/78. 29 gennaio 2001. Disponibile su www.associazioneaglietta.it. 22. ACOG practice bulletin, «Medical management of tubal pregnancy», Number 3, december 1998, «Clinical management guidelines for obstetrician-gynecologist», American College of Obstetricians and gynecologists, Int J Gynaecol Obstet, 1999, 65, pp. 97-103. 23. RCOG Clinical green top guidelines. Tubal Pregnancy. October 2002. 24. J. G. Kahn, B. J. Becker, L. MacIsaac, et al., «The efficacy of medical abortion: a metaanalysis», Contraception, 2000, 61, pp. 29-40. 25. H. C. Pymar, M. D. «Creinin, Alternatives to mifepristone regimens for medical abortion», Am J Obstet Gynecol, 2000, 183, pp. s54-s64. 26. L. Borgatta, M. S. Burnhill, J. Tyson, K. K. Leonhardt, R. U. Hausknecht, S. Haskell, «Early medical abortion with methotrexate and misoprostol», Obstet Gynecol, 2001 Jan, 97(1), pp. 11-16. 27. E. H. Elahi, «Early medical abortion with methotrexate and misoprostol», Obstet Gynecol, 2001 May, 97(5 Pt 1), p. 800. 28. J. L. Carbonell Esteve, L. Varela, A. Velazco, R. Tanda, C. Sanchez, «25 mg or 50 mg of oral methotrexate followed by vaginal misoprostol 7 days after for early abortion: a randomized trial», Gynecol Obstet Invest, 1999, 47(3), pp. 182-187. 29. M. D. Creinin, «Conception rates after abortion with methotrexate and misoprostol», Int J Gynaecol Obstet, 1999 May, 65(2), pp. 183-188. 30. S. M. Harvey, L. J. Beckman, S. J. Satre, «Experiences and satisfaction with providing

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La proposta non trovò obiezioni scientifiche, ma sin dall'inizio l'orientamento fu quello di utilizzare il mifepristone, essendo registrato per questa indicazione e vantando i migliori risultati in letteratura. La polemica insorge due mesi dopo, quando il quotidiano La stampa pubblica la notizia con i commenti favorevoli dei due capi dipartimento, Marco Massobrio e Mario Campogrande, e del direttore sanitario Carmelo Del Giudice.35 Il presidente della regione Piemonte, Enzo Ghigo, decide di rinviare ogni dibattito a dopo le imminenti elezioni politiche e amministrative. Sul piano personale il presidente della Giunta regionale e l'assessore alla Sanità dichiarano di essere contrari all'aborto, evitando però di entrare nel merito di aspetti prettamente medici. Passate le elezioni, il direttore generale del S. Anna, Gianluigi Boveri, prende atto della richiesta dei medici e decide di intraprendere la via della sperimentazione, ritenendo necessario un coinvolgimento del Comitato etico regionale. Sponsor della sperimentazione sarà l'azienda. Vengono quindi accantonate le proposte alternative sul metotrexate e sul misoprostol, e viene creato un gruppo di lavoro, che inizia a lavorare dopo l'estate e che a dicembre presenta il progetto all'azienda. Nel frattempo, la rivista dell'Ordine dei medici di Torino ospita un forum, «RU 486: riflessioni oltre il clamore». Introducendolo, il presidente Amedeo Bianco commenta: «il confronto tra idee e coscienze diverse porta luce nelle pieghe dei nostri vissuti e cresce in tal modo la nostra capacità di convivere con visioni etiche diverse, nel rispetto di ognuno e di tutti».36

L'approvazione

La proposta di sperimentazione viene presentata in Regione l'8 febbraio 2002 e trasmessa l'11 febbraio alla Commissione regionale per le sperimentazioni cliniche, che funge da Comitato etico per il Piemonte. Memmethotrexate-induced abortions among US providers», J Am Med Womens Assoc, 2000, 55(3 Suppl), pp. 161-163. 31. M. D. Creinin, J. L. Carbonell, J. L. Schwartz, L. Varela, R. Tanda, «A randomized trial of the effect of moistening misoprostol before vaginal administration when used with methotrexate for abortion», Contraception, 1999 Jan, 59(1), pp. 11-16. 32. A. R. Davis, L. Mille, H. Tamimi, A. Gown, «Methotrexate compared with mercaptopurine for early induced abortion», Obstet Gynecol, 1999 Jun, 93(6), pp. 904-909. 33. M. Ozeren, C. Bilekli, V. Aydemir, H. Bozkaya, «Methotrexate and misoprostol used alone or in combination for early abortion», Contraception, 1999 Jun, 59(6), pp. 389-394. 34. E. R. Wiebe, «Oral methotrexate compared with injected methotrexate when used with misoprostol for abortion», Am J Obstet Gynecol, 1999 Jul, 181(1), pp. 149-152. 35. M. Accossato, «Al Sant'Anna la pillola abortiva. Primari favorevoli, l'ultima parola alla regione», La stampa, 25 aprile 2001. 36. «RU 486: riflessioni oltre al clamore», Torino Medica, Rivista mensile d'informazione medica, 2001 luglio, 12(7), pp. 5-17.

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bri della Commissione, che è presieduta dall'ingegniere Gianpiero Cerutti, sono il professore Alberto Angeli (professore ordinario di medicina interna ­ Università di Torino), il dottor Luciano Armanni (funzionario dell'Assessorato regionale alla Sanità, esperto di diritto amministrativo), il professore Mario Eandi (professore ordinario di farmacologia dell'Università di Torino), l'avvocato Paolo Emilio Ferreri (avvocato civilista, libero professionista), il dottor Giorgio Lovera (psicologo, dirigente medico ospedaliero dell'Azienda ospedaliera S. Giovanni Battista di Torino), il dottor Antonio Odasso (già sovraintendente sanitario dell'Ospedale Mauriziano di Torino), il professore Angelo Paletto (già professore ordinario di chirurgia generale dell'Università di Torino), il professore Mario Portigliatti Barbos (già professore di medicina legale dell'Università di Torino) e il dottor Domenico Savio (magistrato dell'Ordine giudiziario in posizione di quiescenza). La pratica è la n. 4244. Denominato «Progetto pilota per l'introduzione di una metodica farmacologica per lo svuotamento abortivo dell'utero (IVG, aborto interno e uovo anembrionato)», è firmato da due universitari, Marco Massobrio e Franco Mascherpa, e due medici ospedalieri, Mario Campogrande e Silvio Viale. Allo studio partecipano 100 dei 118 ginecologi assegnati alle sette divisioni; di questi 52 non sono obiettori e 48 sono obiettori. La collaborazione dei medici obiettori si limiterà all'aborto interno e all'uovo anembrionato. Tra di loro vi sono i primari delle sette divisioni; due obiettori e cinque non obiettori. Il protocollo prevede di studiare 400 donne con gravidanza fino a 49 giorni, divise in quattro gruppi, le quali assumeranno due diversi dosaggi di mifepristone, 200 o 600 mg per via orale, e alle quali due giorni dopo verrà somministrato il misoprostol con due modalità, 400 mcg per via orale o 800 mcg per via vaginale, e con una eventuale seconda somministrazione di misoprostol per via orale, se non dovesse essere avvenuta l'espulsione del prodotto abortivo durante le quattro ore del periodo di osservazione. Nel mese di aprile, in un incontro tra gli sperimentatori, l'Azienda e i membri del Comitato etico, viene consigliato di limitare lo studio alle IVG e di precisare meglio alcuni aspetti della documentazione. Si procede quindi a ridefinire il progetto, che viene consegnato il 6 settembre 2002, e sottoposto al Comitato etico il 9 settembre. La nuova denominazione è, «IVG con mifepristone (RU 486) e misoprostol». I presentatori sono sempre gli stessi quattro e i partecipanti allo studio sono 51 ginecologi non obiettori. Tra di loro cinque primari: Marco Massobrio, Chiara Benedetto, Tullia Todros, Ruggero Grio e Mario Campogrande. Tutti i documenti sono stati rivisti, accogliendo le osservazioni dei membri del Comitato etico.

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Il progetto viene approvato il 28 ottobre 2002, a maggioranza, dalla Commissione regionale per le sperimentazioni cliniche, subordinatamente al completamento della pratica per quanto riguarda il giudizio di notorietà sull'associazione dei due prodotti utilizzati nel protocollo, cioè l'attestazione che i medicinali siano già stati utilizzati sull'uomo in rapporto all'indicazione terapeutica proposta, e in riferimento alle modalità di copertura delle spese sperimentali. Si registra un voto contrario, mentre il membro indicato dal presidente della Corte d'Appello di Torino si assenta al momento della votazione. A questo punto, per l'importazione del mifepristone, mancano l'acquisizione del principio di notorietà e la delibera conclusiva dell'azienda.

L'ispezione

A poche ore dalla diffusione della notizia dell'approvazione il ministro della Salute, Girolamo Sirchia, annuncia che sarà la CUF a verificare i requisiti di sicurezza ed efficacia della sperimentazione,37 dimenticando che è di competenza del Comitato etico38 e che, trattandosi di due farmaci registrati, si tratta di una pura formalità. Il giorno dopo deve ammettere che il farmaco «non è poi così tossico», che è «gia sperimentato» e che «non c'è nulla da scoprire»,39 ma il giorno successivo, il 30 ottobre, il direttore del Dipartimento farmaci del Ministero della salute, Nello Martini, chiede di acquisire tutta la documentazione, e il ministro annuncia l'invio degli ispettori, precisando che si tratta di una «normale attività» di controllo.40 In realtà è la prima volta che l'ufficio ispezioni, sorto nel 2000, si occupa di una sperimentazione non ancora iniziata,41 ma le finalità delle ispezioni sono il perfezionamento dello studio e la verifica di quanto previsto dalle regole di Buona pratica clinica,42 e l'attività ispettiva rientra nei poteri di iniziativa della Direzione generale della valutazione dei medicinali e della farmacovigilanza. Gli ispettori si recano il 26 novembre 2002 alla sede del Comitato etico della regione Piemonte e dall'11 al 13 dicembre 2002 all'Ospedale S. Anna.

37. M. Tropeano, La stampa, 29 ottobre 2002. O. Giustetti, La repubblica, 29 ottobre 2002. 38. Decreto ministeriale 18 marzo 1998, recante modalità per l'esenzione dagli accertamenti sui medicinali utilizzati nelle sperimentazioni cliniche. GU 28 maggio 1998 n. 122. 39. S. Deligia, Liberazione, 30 ottobre 2002. 40. F.A. Il giornale, 1 novembre 2002. 41. Decreto ministeriale 3 gennaio 2000. Accertamenti ispettivi sull'osservanza delle norme di buona pratica clinica. 42. Decreto ministeriale 15 luglio 1997. Recepimento delle linee guida della U.E. di Buona Pratica Clinica per la esecuzione delle sperimentazioni cliniche dei medicinali.

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Il 27 gennaio 2003 viene inviato il verbale relativo all'ispezione, sottolineando i punti carenti riscontrati, comunicando di far pervenire la documentazione per le successive determinazioni «almeno 60 giorni prima dell'avvio della sperimentazione» e richiamando «la necessità di attendere i pareri richiesti all'Ufficio legislativo di questo Ministero, per quanto concerne la pertinenza della sperimentazione con quanto previsto dalla legge 194/78 e le modalità di copertura delle spese di sperimentazione». Il parere dell'Ufficio legislativo del Ministero della salute viene inviato il giorno successivo e con esso viene sostenuto, in via interlocutoria, che non è ancora possibile esprimere un giudizio di totale compatibilità, riprendendo quanto era già stato riferito dal Corriere della sera un mese prima in relazione a una inchiesta aperta dal procuratore aggiunto Raffaele Guariniello.43 La tesi è che la 194 prescriva che l'aborto debba avvenire in ospedale o nei poliambulatori, mentre con la RU 486 l'espulsione del prodotto abortivo in una parte dei casi avviene a domicilio. Il Ministero sembra farne una questione di sicurezza, ritenendo che la donna debba rimanere ricoverata fino a completa espulsione avvenuta, che sarebbe l'opinione di Raffaele Guariniello, riportata dal Corriere della sera. Svolgendosi tutto in ospedale, l'uso della RU 486 non sarebbe in contrasto con la legge 194,44 ma ne verrebbero limitati la logica contro ogni ragionevolezza medica, non impedendo però la sperimentazione. L'Ospedale S. Anna ha successivamente perfezionato il progetto, accogliendo tutte le prescrizioni degli ispettori, che il 19 marzo 2003 e stato inviato sia al Ministero che al Comitato etico, allegando i testi comparati delle ulteriori modifiche apportate, le controdeduzioni alla relazione inviata dagli ispettori del Ministero della salute e le osservazioni al parere dell'Ufficio legislativo del Ministero della salute, per quanto riguarda la conformità con la 194/78. Inoltre ha inviato agli ispettori la nota del 28 novembre 2002, con la quale si indicavano al Comitato etico le modalità di copertura delle spese della sperimentazione, dichiarando che il costo della sperimentazione sarà inferiore a quello ordinariamente sostenuto per il servizio di IVG, anche se il rimborso per DRG «aborto senza intervento chirurgico» è circa la metà di quello previsto per l'«aborto con intervento chirurgico». Al Comitato etico sono inviate l'Investigator's Brochure del mifepristone, fatta pervenire dai Laboratoires Exelgyn di Parigi, e la lettera dell'azienda farmaceutica titolare dell'autorizzazione in commercio in Italia del misoprostol, ai fini di ottenere l'attestato di notorietà dei due farmaci.

43. M. Pappagallo, «La pillola per abortire: per il PM test illegale», Il corriere della sera, 16 dicembre 2002. 44. D. Monti, M. Pappagallo, «Parere del ministero della salute: la Ru 486 sia usata solo in ospedale. «Pillola abortiva, sperimentazione illegale»», Il corriere della sera, 1 febbraio 2003.

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In data 28 aprile 2003 il dirigente dell'Ufficio ispezioni del Ministero ha comunicato di essere in attesa del parere definitivo dell'Ufficio legislativo del Ministero, aggiungendo che «la sperimentazione potrà essere avviata solo se l'Ufficio legislativo la ritiene conforme alla 194/78, per cui è necessario attendere le relative osservazioni». Da parte sua il Comitato etico, nelle sedute del 16 giugno 2003 e del 21 luglio 2003, ha preso atto delle modifiche apportate, comunicando di non avere ancora sciolto le riserve formulate sui costi della sperimentazione, nonché sul giudizio di notorietà, in attesa che il Ministero della salute sciolga le sue riserve per quanto di sua competenza. Con l'ultima modifica apportata allo studio sono stati aboliti i bracci sperimentali per la somministrazione endovaginale del misoprostol, poiché la Exelgyn nel mese di marzo aveva comunicato che non avrebbe fornito il farmaco se si fosse mantenuta la via vaginale, perché non fa parte dei piani dell'azienda avallare tale via di somministrazione. Il Comitato etico ha preso atto che, con questa ulteriore modifica al protocollo, lo studio acquisisce ulteriore sicurezza, adottando quello in uso in Francia da 14 anni e limitandosi a confrontare due dosaggi diversi del mifepristone.

La situazione attuale

Con l'ultima comunicazione del capo degli ispettori, Umberto Filibeck, il Ministero ha accentuato un certo ruolo politico, estraneo ai poteri ispettivi, inserendosi in modo improprio nel percorso autorizzativo della sperimentazione. Non vi era necessità di un imperativo così diretto, poiché l'Ospedale S. Anna e il Comitato etico avevano comunicato di attendere l'esito finale dell'ispezione, anche per approfittare di un autorevole contributo legale su una materia oggetto di forti polemiche. Sembra invece che il Ministero tema un eventuale inizio della sperimentazione, come conseguenza del possibile dilungarsi dell'ispezione, per le cui determinazioni si è già andati ben oltre i 60 giorni che ci si era riservati. Ma se era ragionevole il periodo di attesa di 60 giorni, non si capisce la ragione di una subordinazione assoluta e illimitata a un parere «definitivo» dell'Ufficio legislativo del Ministero, il cui compito non è precisamente quello di dare interpretazioni autentiche alle leggi. Infatti, non essendoci ancora una giurisprudenza consolidata, né precise disposizioni di legge, sarà certamente utile il contributo, su cui l'ufficio legale sta lavorando dal dicembre scorso, tenendo presente che il S. Anna ha trasmesso le proprie osservazioni sin dal marzo scorso e ha teso a superare ulteriormente le preoccupazioni esposte, ma le finalità che la legge

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assegna agli ispettori possono essere esercitate con ulteriori successive ispezioni durante tutte le fasi dello studio clinico. Il rischio di una pausa infinita finirebbe per assumere connotati strumentali e intimidatori, inducendo il Comitato etico a sospendere di fatto i propri lavori. La questione dei costi e quella dell'esenzione dagli accertamenti dell'Istituto superiore di sanità (ISS) sarebbero già state risolte, se non fosse intervenuta la fase ispettiva e la richiesta di attesa. Il parere legale, richiesto dagli ispettori all'ufficio legale del proprio Ministero, non può nemmeno essere messo in relazione con la legittima indagine della procura torinese, che potrebbe anche portare a iniziative nei confronti dei promotori della sperimentazione, dell'Azienda del S. Anna o del Comitato etico, non esistendo alcun collegamento tra i compiti di sorveglianza sulle sperimentazioni del Ministero e gli obblighi di indagine della magistratura. Da questo punto di vista la questione della non compatibilità con la 194 sollevata dal Ministero appare un'ipotesi un po' strumentale, più politica che medico legale, come evidenzia anche il fatto che non sia stata mai sollevata prima, durante la lunga istruttoria del Comitato etico, che è di indiscusso ottimo livello per competenze, per esperienze e per qualità professionali, e che ha visto manifestare al suo interno anche pareri contrari alla sperimentazione. Rimangono quindi aperte la questione dei costi della sperimentazione, quella del principio di notorietà e quella della compatibilità con la 194 in relazione al luogo dell'aborto.

I costi

Sulle modalità di copertura dei costi della sperimentazione gli ispettori hanno chiesto un parere al proprio ufficio legislativo, che non è ancora pervenuto. La legge regionale recita che «i costi, sia diretti che indiretti, derivanti dalle attività di sperimentazione clinica, sono a carico dello sponsor o di specifici fondi di ricerca e non devono gravare sul bilancio del Servizio sanitario, a eccezione di quelli che, pur inclusi nella sperimentazione, non costituendo spesa aggiuntiva in quanto parte di trattamenti, terapie e interventi consolidati, sono normalmente erogati in regime di assistenza sanitaria per la specifica patologia oggetto della sperimentazione». L'attività di IVG rientra pienamente nell'eccezione e i costi, che l'azienda dovrà affrontare per i 400 casi di aborto medico, sono inferiori a quelli che oggi ha per 400 casi di aborto chirurgico, sia per quanto riguarda la quantità di personale impiegato, che in riferimento all'impegno delle strutture e dei servizi necessari, per cui la sperimentazione comporta un

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risparmio e non un aggravio sul bilancio, nonostante necessiti di una organizzazione aggiuntiva rispetto a quella che comporterebbe la semplice introduzione del metodo medico nella pratica clinica. A tale proposito, è da notare che l'esperienza europea dimostra una riduzione dei costi nel settore pubblico, con un progressivo aumento delle attività ambulatoriali in Francia e la decisione del Ministero della sanità britannico di favorire l'aborto medico nelle strutture territoriali. Tornando alla sperimentazione, è chiaro che l'Ospedale S. Anna non può accantonare fondi per la ricerca, ma deve utilizzare quelli normalmente destinati alla specifica attività («patologia») che è oggetto della sperimentazione, senza spendere di più. Se si dovesse adottare un'interpretazione restrittiva, con la richiesta di un capitolo di fondi aggiuntivi, questo comporterebbe l'impossibilità di una ricerca autonoma sponsorizzata da una azienda sanitaria, che non dovesse trovare sponsor per motivi di discriminazione politica. L'esigenza di valutare metodi nuovi, meno invasivi, nasce anche dalla specificità dell'Ospedale S. Anna, che effettua un alto numero di IVG, 440 IVG ogni 1.000 parti, con il 36 per cento delle 3.700 IVG di donne straniere, che sono il 14 per cento degli 8.400 parti.45 Sarebbe quindi curioso che si contestasse la spesa dello studio, che è inferiore a quanto si spende per l'attività ordinaria, e che sopperisce pure alle inadempienze della regione, che dovrebbe spendere ben di più per promuovere l'aggiornamento previsto dall'articolo 15 della 194, «sull'uso delle tecniche più moderne, più rispettose dell'integrità fisica e psichica della donna e meno rischiose per l'interruzione della gravidanza». Come potrebbe tale aggiornamento evitare di affrontare le tecniche mediche?

Il principio di notorietà

La questione è nelle mani dell'esperto farmacologo del Comitato etico, Mario Eandi, professore ordinario di farmacologia presso l'Università di Torino. La legge prevede che l'esenzione dagli accertamenti dell'ISS venga richiesta al Comitato etico, documentando che «per il medicinale sono disponibili sufficienti dati relativi alla qualità e alla sicurezza nell'uomo, in rapporto alla indicazione terapeutica proposta per la sperimentazione clinica», e rientrando in almeno una delle «condizioni di affidabilità» indicate all'allegato 1 del DM 18 marzo 1998.

45. G. Rabacchi, «Prestazioni in crescita», OIRM-S.Anna Notiziario, 2003, 2, pp. 10-11.

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La prima di queste condizioni di affidabilità è che il farmaco sia già stato autorizzato all'immissione in commercio in uno o più paesi dello Spazio economico europeo, oppure in Australia, in Canada, in Nuova Zelanda o negli Stati Uniti; condizione ampiamente soddisfatta dalle autorizzazioni all'immissione in commercio in molti paesi dell'Unione europea46 e dalla procedura di mutuo riconoscimento.47 Conseguentemente sono soddisfatte anche le altre tre condizioni di affidabilità che prevedono l'esistenza di sperimentazioni con risultati favorevoli, l'avvenuta autorizzazione a sperimentazioni o l'utilizzo, comprovato dai dati della letteratura scientifica internazionale, con risultati favorevoli per qualità e sicurezza nell'uomo. Come documentazione, al progetto di studio è allegata una selezione di 85 lavori tratti dalla letteratura internazionale degli anni 2000 e 2001, l'Investigator's Brochure fornita dalla Exelgyn,48 una lettera della ditta titolare del misoprostol e il fascicolo relativo all'approvazione da parte della FDA il 28 settembre 2000.49 Si dovrebbe quindi trattare di una pura formalità.

La compatibilità con la 194

A partire dalla previsione che il 30-35 per cento delle donne espellerà il prodotto abortivo dopo il periodo di osservazione in ospedale, «pur non essendo compito delle ispezioni di Buona pratica clinica entrare nel merito dell'osservanza o meno di norme di carattere generale», gli ispettori hanno ritenuto di richiamare l'attenzione sulla compatibilità con l'articolo 8 della 194, che recita «l'interruzione della gravidanza è praticata da un medico del servizio ostetrico-ginecologico presso un ospedale generale [...] il quale verifica anche l'inesistenza di controindicazioni sanitarie». Gli ispettori hanno sottolineato le parole «praticata» e «pres46. Autorizzazioni immissioni al commercio paesi Unione europea. Austria n. 1-23220 21 settembre 1999; Belgio n. 2 532IE 1 F3 22 novembre1999; Danimarca n. 30 741 27 agoato 1999; Finlandia n. 14046 20 dicembre 1999; Francia n. 556 473.0 28 dicembre 1988; Germania n. 46 038.00.00 19 agosto 1999; Grecia n. 2455001 10 ottobre 1999; Lussemburgo n. 118 00 11 0052 11 dicembre 2000; Olanda n. RVG 24 206 25 agosto 1999; Spagna n. 62 728 21 ottobre 1999; Svezia n. 11642 4 settembre 1992; Regno unito n. PL 16152 0001 1 luglio 1991. 47. Procedura europea di mutuo riconoscimento FH/H/137/01 presentata il 6 aprile 1999 e approvata il 6 luglio 1999. 48. Investigato's Brochure. English version 1999. Inviata dalla Exelgyn, su richiesta dell'Ospedale S. Anna, nel gennaio 2003 in via confidenziale per i rapporti con l'autorità sanitaria. 49. FDA. Center for drug evaluation and research. Approval Package. Application number: 20687. Trade name: Mifeprex. Generic name: mifepristone. Sponsor Sponsor Population Council. 28 Sep 2000N Offices of public affairs. FDA approves mifepristone for termination of early pregnancy. Hhs News Info-FDA, 28 sep 2000. www.fda.gov

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so un ospedale». Un'analoga preoccupazione, in alcuni articoli di giornale, è stata anche attribuita al procuratore aggiunto Raffaele Guariniello. L'ipotesi è che la 194 prescriva che l'aborto debba avvenire dentro l'ospedale. L'ufficio legislativo del Ministero, in via interlocutoria, ha osservato come «gli inevitabili effetti abortivi differiti nel tempo, rispetto a quelli immediati propri dell'intervento chirurgico, faccia emergere un profilo di potenziale incompatibilità della sperimentazione proposta con l'articolo 8 della legge n. 194». Tale preoccupazione legale non era mai emersa prima da parte dell'Assessorato alla sanità del Piemonte nella stesura della risposta all'interpellanza del gruppo radicale, 20 né durante la preparazione del progetto da parte dei medici dell'Ospedale S. Anna, certamente competenti ed esperti in tema di applicazione della 194, e neppure da parte degli esperti presenti nel Comitato etico piemontese. Solo il Movimento per la vita, nelle sue polemiche, aveva prospettato una generica incompatibilità con la 194 della pillola abortiva. Pur considerando che non esiste una giurisprudenza consolidata, con precise disposizioni di legge, eccetto il precedente della sperimentazione milanese di Pier Giorgio Crosignani, l'ipotesi interpretativa interlocutoria del Ministero della salute non sembra essere fondata. La legge 194 infatti non entra mai nel merito delle modalità tecniche di esecuzione dell'interruzione di gravidanza, se non con l'articolo 15, quando però prevede espressamente l'aggiornamento sulle tecniche «più moderne», che è riconosciuto anche dal capo dell'ufficio legislativo quando afferma che «questa tecnica [...] risulta comunque coerente [...] con la specifica previsione dell'articolo 15». Quando nella legge si parla di «intervento», non vi è alcuna possibilità di limitarlo esclusivamente a quello strumentale chirurgico, poiché in medicina si intende con esso la generica azione medica che può essere effettuata con strumenti chirurgici, farmacologici, fisici, psicologici, comportamentali, fisiatrici e altri ancora, e le cui modalità temporali e cronologiche sono di competenza del «medico del servizio ostetricoginecologico presso un ospedale», in scienza e coscienza. Con riferimento agli aspetti semantici e logici del primo comma dell'articolo 8, esso deve essere letto e inteso nella sua semplice conseguenzialità grammaticale ove le parole «presso un ospedale» qualificano la figura del ginecologo. L'«interruzione di gravidanza», cioè l'atto medico idoneo a porre fine alla sua evoluzione, senza precisare tempi, luoghi e modalità, è «praticata» da un medico, che è responsabile dell'applicazione di quanto previsto dalla legge, dell'avvenuto rispetto formale delle procedure autorizzative e della verifica delle «controin-

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dicazioni sanitarie». Colui che pratica l'IVG è individuato nel «medico del servizio-ostetrico ginecologico presso un ospedale generale», e non in un altro medico. La preposizione di luogo «presso» si riferisce inequivocabilmente al «medico», che deve fare parte del «servizio ostetrico ginecologico» dell'ospedale che pratica l'IVG. Il verbo praticare ha il significato generico che deriva dalla nozione di «pratica medica», cioè mettere in atto o eseguire, senza avere connotazioni di tempo o di spazio. E' chiaro che la preoccupazione del legislatore è di limitare l'intervento abortivo alla pratica di un medico dell'ospedale, ma non entra nel merito dei tempi, del luogo e delle modalità della sua esecuzione. In nessun punto afferma che debba avvenire e concludersi continuativamente in ospedale. Se il legislatore avesse voluto indicare l'obbligo di rimanere in ospedale per tutto il procedimento abortivo, lo avrebbe indicato esplicitamente, definendo anche quando lo si sarebbe dovuto considerare concluso e avrebbe previsto una sanzione per la donna che, concluse «le attività specificamente e necessariamente dirette a determinare l'interruzione della gravidanza», rinunciasse all'assistenza conseguente, abbandonando l'ospedale. Non si può nemmeno rifugiare nella presunzione che nel 1978 ci si riferisse esclusivamente all'aborto chirurgico, poiché esisteva già la possibilità di indurre l'aborto con farmaci, che non poteva non essere nota al legislatore, il quale ha ritenuto proprio per questo di non entrare nel merito delle modalità abortive, evitando accuratamente ogni riferimento sia alle metodiche chirurgiche, all'epoca elettive per l'IVG del primo trimestre, o a quelle mediche, all'epoca elettive per le IVG del secondo trimestre. Anche se nel 1978 non esistevano ancora le USL (legge 833/78), erano già stati istituti i consultori familiari (legge 405/75) e gli obiettivi delle autorità sanitarie erano già quelle di ridurre l'impegno dell'ospedale e in coerenza la 194 prevede la possibilità di fare le IVG nei poliambulatori territoriali. E' noto che gran parte delle attività mediche e chirurgiche, analoghe alle IVG, che allora si svolgevano in regime di ricovero, oggi avvengono in day hospital, in day surgery, in day service, in regime ambulatoriali e anche a domicilio. Solo agli albori all'epoca, in questi anni si è sviluppata la tecnica ecografia, che permette diagnosi molto più precise nelle prime settimane della gravidanza. Nello specifico caso dell'IVG con metodo medico ogni ginecologo sa che l'espulsione del prodotto abortivo è la conseguenza di un procedimento

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precedente, che ha interrotto la gravidanza, e che ha comunque completato la parte attiva e volontaria. Nel caso dell'aborto chirurgico i due momenti sono generalmente immediatamente successivi, mentre per l'aborto con farmaci «il medico del servizio ostetrico-ginecologico presso un ospedale generale» si limita a prescrivere i farmaci e a controllarne l'assunzione da parte della donna. In entrambi i casi il decorso, successivo alle «attività specificamente e necessariamente dirette a determinare l'interruzione della gravidanza», è soggetto alle autonome valutazioni mediche in relazione all'evoluzione del quadro clinico. Nella fattispecie il decorso è analogo a quello di un aborto spontaneo di epoca gestazionale corrispondente, per la gestione del quale non mi pare esistano specifiche prescrizioni di legge. Per ovviare alla debolezza di una interpretazione giuridico-formale sull'incompleta realizzazione degli interventi di IVG in ambiente ospedaliero, il capo dell'ufficio legislativo propone una valutazione medica sulla pericolosità delle conseguenze, «soprattutto per i rischi che, proprio da tale conosciuta e preventiva eventualità, possano derivare per la salute delle pazienti, in relazione alle meno sicure e protette condizioni sanitarie in cui dovessero trovarsi ad affrontare l'aborto, lontane dalle strutture sanitarie e in carenza dei relativi controlli medico-specialistici». Rendendosi probabilmente conto di avventurarsi su terreno scivoloso, viene invocato il paradosso che «sarebbe difficile sostenere, del resto, che siffatta preoccupazione sia stata estranea al legislatore in sede di formulazione dell'articolo 8», come se fosse possibile per il legislatore una preoccupazione contraria, o che temesse che per l'aborto volontario non si potesse ricorrere alle ordinarie procedure di pronto intervento e di assistenza, che peraltro in questi anni si sono notevolmente sviluppate e potenziate. Si tratta di una legittima preoccupazione sanitaria, che però non può essere posta in astratto, ma deve valutare concretamente se le potenziali ipotizzabili complicazioni corrispondano a una previsione di entità maggiore e sproporzionata rispetto ad altre situazioni cliniche, che colgono la donna fuori da un ospedale con il consenso medico, non potendosi ritenere che il legislatore abbia voluto fornire alle donne, coinvolte in altre situazioni cliniche, una tutela minore di quella offerta in caso di aborto volontario. Sotto questo profilo, i consulenti medici del Ministero non potranno che confermare, che i potenziali rischi connessi all'espulsione del prodotto abortivo non sono maggiori di quelli che comportano le attuali ordinarie dimissioni, dopo un parto spontaneo o cesareo, un aborto (completo o incompleto), un'IVG chirurgica (prima e dopo il 90° giorno), un'IVG farmacologica con prostaglandine (prima e dopo il 90° giorno), una gravi-

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danza extrauterina (risolta o non risolta) o una minaccia di aborto, per rimanere in stretto ambito ostetrico. Cioè, con perdite ematiche in atto, con rischio di aumento consistente delle stesse, con perdita di coaguli, di frammenti di mucosa o di materiale ovulare, ovvero con pericolo di ematometra, di shock ipotensivo anche conseguente al potenziale insorgere di un addome acuto, con pericolo di vita. Basti accennare anche a tutte le dimissioni precoci, giornaliere degli interventi eseguiti in laparoscopia o in day surgery. Si tratta delle stesse complicazioni acute, che possono insorgere in ogni epoca gestazionale, in gravidanze «normali» o «a rischio», e che vengono affrontate con gli ordinari presidi di pronto intervento territoriali e ospedalieri. Al contrario, i rischi connessi a un aborto medico delle prime settimane di gestazione è minore, proprio per l'epoca gesatazionale minore e per l'assenza delle potenziali complicazioni chirurgiche. Non stupisce quindi che l'estensore del parere concluda che «[...] allo stato attuale questo Ufficio non ritiene ancora possibile esprimere un giudizio di totale compatibilità con detta legge della sperimentazione in esame fino a quando i relativi protocolli clinici non risultino in grado di assicurare a quelle pazienti, le cui interruzioni volontarie di gravidanza conseguenti a trattamento farmacologico avvengano al di fuori delle strutture sanitarie, garanzie di tutela contro i potenziali rischi della loro condizione equivalenti a quelle offerte alle pazienti assistibili, agli stessi fini, in sede ospedaliera». Se questa è la preoccupazione del Ministero, cioè la tutela delle donne partecipanti alla sperimentazione, essa è destinata a essere superata, poiché i medici del S. Anna hanno predisposto per queste donne condizioni di assistenza superiori a quelle che da 25 anni si sottopongono all'IVG chirurgica. Sull'aspetto della sicurezza il protocollo proposto è confortato da una ampia letteratura internazionale, dalle linee guida di molte organizzazioni mediche e dall'applicazione del metodo in ormai un milione di casi nei soli paesi della Comunità europea e negli Stati Uniti. In tutti i paesi dove l'aborto con la RU 486 è entrato nella pratica clinica, la tendenza è di renderlo sempre più extraospedaiero, e in nessun caso, per l'aborto fino a 49 giorni, è prescritta la permanenza in ospedale oltre le 3-4 ore del periodo di osservazione. Pertanto il fatto che la metrorragia abortiva insorga fuori dall'ospedale in una parte dei casi e persista dopo le dimissioni in tutti i casi, non configura un pericolo eccessivo o una incompatibilità giuridica con la 194. Anzi, non informare la donna su questa possibilità è in contrasto con quanto previsto all'articolo 14 sul dovere di informazione dei «pro-

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cessi abortivi» e con la normativa sul consenso informato e il diritto di scelta consapevole dei procedimenti medici. E' difficile sostenere che la legge imponga una sola «alternativa», la più invasiva, basandosi solo su una distorsione grammaticale della preposizione «presso».

L'aspetto medico

La storia dell'aborto medico inizia negli anni cinquanta, utilizzando con successo l'aminopterina, un antagonista dell'acido folico,50 ma è agli inizi degli anni settanta che la ricerca riprende con l'introduzione delle prostaglandine naturali (PGE2 e PGF2), ma gli effetti collaterali sono molto pesanti.51, 52 La sintesi di analoghi delle prostaglandine, come il gemeprost o il sulprostone, dà un nuovo impulso ma i sintomi gastrointestinali rimangono severi.53,54,55 Così le prostaglandine sono perlopiù utilizzate per preparare l'aborto chirurgico o per indurre quelli delle gravidanze più avanzate. Si capisce che altri farmaci possono avere un effetto abortivo, che aumenta con la somministrazione successiva di una prostaglandina. A questo scopo si sono utilizzati il metotrexate,24-34 inibitori della sintesi del progesterone come l'epostano56,57 o il trilostano,58

50. J. B. Thiersch, «Therapeutic abortion with a folic acid antagonist 4-aminopteroyglutamic acid (a-amino PGA) administered by oral route», Am J Obstet Gynecol, 1952, 63, pp. 12981304. 51. S. M. M. Karim, «Once a month vaginal administration of prostaglandin E2 and F2 for fertilità control», Contraception, 1971, 3, pp. 173-183. 52. P Mocsary, A. J. Csapo, «Menstrual induction with PGE2 and PGF2. Prostaglandins», 1975, . 10, pp. 545-547. 53. S. K. Smith, D. T. Baird, «The use of 16,16-dimethyl-trans-PGE1 metuyl ester (ONO 802) vaginal suppositories for the termination of early pregnancy: a comparative study», Br J Obstet Gynaecol, 1980, 87, pp. 812-817. 54. I. T. Cameron, D. T. Baid, «Early pregnancy termination: a comparative study between vacuum aspiration and medical abortion with prostaglandins (16,16-dimethyl-trans-PGE1 metuyl ester) or the progestogen RU 48», Br J Obstet Gynaecol, 1988, 95, pp. 271-276. 55. Anonimo, «Menstrual regulation by intramuscular injection of 16-phenoxy-tetranor PGE2 methyl sulfonylamide or vacuum aspiration: a randomized multicenter study. World Health Organization. Task force on Post-ovulatory methods for Fertility Regulation», Br J Obstet Gynaecol, 1987, 94, pp. 949-956. 56. L. Birgerson, V. Odlind, «Early pregnancy termination with antiprogestins: a comparative clinical study of RU 486 given in two dose regimens and Epostane», Fertil Steril, 1987 Oct, 48(4), pp. 565-570. 57. M. J. Crooij, C. C. A. de Noofer, B. R. Rao, G. T. Berends, L. J. G. Gooren, J. Jansens, «Termination of early pregnancy following by the 3-hydroxysteroid dehydrogenase inhibitor epostane», N Engl J Med, 1988, 319, pp. 813-818. 58. P A. Roux, S. K. Tregoning, P M. Zinn, Z. M. Van DerSpuy, «Inhibition of progesterone . . secretion with trilostano for mid-trimester termination of pregnancy: randomized controlled trials», Hum Reprod, 2002 Jun, 17(6), pp. 1483-149.

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antiestrogeni come il tamoxifene59-61 o il misoprostol da solo.62-73 Il misoprostol è sempre più utilizzato per indurre gli aborti illegali nei paesi dove è vietato.74-77 Ma il farmaco principe dell'aborto medico è il mifepristone, che viene scoperto agli inizi degli anni ottanta da Etienne Emile Baulieu per la Roussel-Uclaf.78 Si tratta di un anticorticoide con una forte affinità per i

59. D. R. Jr Mishell, J. K. Jain, J. D. Byrne, M. D. Lacarra, «A medical method of early pregnancy termination using tamoxifen and misoprostol», Contraception, 1998 Jul, 58(1), pp. 1-6. 60. J. K. Jain, K. R. Meckstroth, M. Park, D. R. Jr Mishell, «A comparison of tamoxifen and misoprostol to misoprostol alone for early pregnancy termination», Contraception, 1999 Dec, 60(6), pp. 353-356. 61. E. R. Wiebe, «Tamoxifen compared to methotrexate when used with misoprostol for abortion», Contraception, 1999 Apr, 59, 265-270. 62. J. L. Carbonell, J. Rodriguez, S. Aragon, A. Velasco, R. Tanda, R. Sanchez, S. Barambio, S. Chami, F. Valero, «Vaginal misoprostol 1000 microg for early abortion», Contraception, 2001 Mar, 63(3), pp. 131-136. 63. A. B. Goldberg, M. B. Greenberg, P D. Darney, «Misoprostol and pregnancy», N Engl J . Med, 2001, 344, pp. 38-47. R. W. Hale, S. Zinberg, «Use of misoprostol in pregnancy», N Engl J Med, 2001 Jan 4, 344(1), pp. 59-60. 64. A. Velasco, L. Varela, R. Tanda, C. Sanchez, S. Barambio, S. Chami, F. Valero, S. Aragon, J. Mari, J. L. Carbonell, «Misoprostol for abortion up to 9 weeks' gestation in adolescents», Eur J Contracept Reprod Health Care, 2000 Dec, 5(4), pp. 227-233. 65. E. R. Wiebe, «Misoprostol administration in medical abortion. A comparison of three regimens», J Reprod Med., 2001 Feb, 46(2), pp. 125-129. 66. K. Blanchard, B. Winikoff, K. Coyaji, T. N. Nguyen, «Misoprostol alone. A new method of medical Abortion?», J Am Womens Assoc, 2000, 55(suppl 3), pp. 189-190. 67. A. Bugalho, A. Mocumbi, A. Faùndes, E. David, «Termination of pregnancy of <6 weeks gestation with a single dose of 800 mcg of vaginal misoprostol», Contraception, 2000 Jan, 61(1), pp. 47-50. 68. J. L. Carbonell, L. Varela, A. Velazco, R. Tanda, S. Barambio, S. Chami, «Vaginal misoprostol 600 microg for early abortion», Eur J Contracept Reprod Health Care, 2000 Mar, 5(1), pp. 46-51. 69. S. W. Ngai, O. S. Tang, Y. M. Chan, P C. Ho, «Vaginal misoprostol alone for medical abor. tion up to 9 weeks of gestation: efficacy and acceptability», Hum Reprod, 2000 May, 15(5), pp. 1159-1162. 70. J. Song, «Use of misoprostol in obstetrics and gynecology», Obstet Gynecol Surv, 2000 Aug, 55(8), pp. 503-510. Review. 71. J. L. Carbonell, L. Varela, A. Velazco, R. Tanda, E. Cabezas, C. Sanchez, «Early Abortion with 800 _g of misoprostol by the vaginal route», Contraception, 1999, 59(4), pp. 219-225. 72. J. K. Jain, C. Dutton, B. Harwood, K. R. Meckstroth, D. R. Mishell, «A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol alone for elective termination of pregnancy», Hum Reprod, 2002, 17(6), pp. 1477-1482. 73. K. Blanchard, B. Winikoff, C. Ellertson, «Misoprostol used alone for the termination of early pregnancy. A review of the evidence», Contraception, 1999 Apr, 59, pp. 209-217, Review. 74. S. Christin-Maitre, P Bouchard, I. M. Spitz, «Medical termination of pregnancy», N Engl J . Med, 2000 Mar 30, 342(13), pp. 946-956. Review. 75. J. Song, «Use of misoprostol in obstetrics and gynecology», Obstet Gynecol Surv, 2000 Aug, 55(8), 503-510. Review. 76. M. A. Rosing, C. D. Archbald, «The knowledge, acceptability, and use of misoprostol for self-induced medical abortion in an urban US population», J Am Womens Assoc, 2000, 55(3 suppl), pp. 183-185. 77. S. H. Costa, «Commercila availability of misoprostol and induced abortion in Brazil», Int J Gynaecol Obstet, 1998, 63(Suppl 1), pp. S131-S139.

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recettori del progesterone, che viene inizialmente indicato con la sigla RU 38486. Dopo vari tentativi si scopre che aggiungendo piccole dosi di una prostaglandina si ha un aborto completo.79 Dal 1988 è in commercio con il nome di Mifegyne®. Che si tratti di un metodo sicuro ed efficace è ormai pressoché incontestabile, essendo considerato tale dall'OMS80-90 e inserito nelle linee guida delle più accreditate organizzazioni mediche, limitandosi a citare quelle dell'American College of Obstetricians and Gynecologists,91 del Royal College of Obstetricians and Gynaecolgists92 e della francese Agence Nationale d'Accreditation et d'Evalutation en Santè.93 L'ACOG attribuisce il grado A, cioè il livello di maggior evidenza scientifica secondo l'US Preventive Services Task For78. E. E. Baulieu, The «Abortion Pill», New York, Simon & Schuster, 1991. 79. M. L. Swahn, S. Cekan, G. Wang, V Lujndstron, M. Bygdeman, «Pharmacokinetics and clini. cal studies of RU 486 for fertility regulation», in: E. E. Baulieu, S. Siegel, ed. The Antiprogestin Steroid RU 486 and Human Fertility Control. New York, NY: Plenum; 1985, pp. 249-258. 80. WHO, «Pregnancy termination with mifepristone and gemeprost: a multicenter comparaison betwen repeated doses and a eingle dose of mifepristone», Fert Steril, 1991, 56, pp. 32-34. 81. WHO, «Task Force on Post-Ovulatory Methods of Fertility Regulation. Menstrual regulation by mifepristone plus prostaglandin: results from a multicentre trial», Hum Reprod, 1995 Feb, 10(2), pp. 308-314. 82. WHO, «Task Force on Post-ovulatory Methods of Fertility Regulation. Termination of pregnancy with reduced doses of mifepristone», BMJ, 1993 Aug, 307, pp. 532-57. 83. WHO, «Scientific Group report. Medical methods for termination of pregnancy», WHO Tech Rep Ser, 871 Geneva 1997, 871, pp. 1-110. 84. WHO, «Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial», Lancet, 1999, 353, pp. 697-702. 85. WHO, «World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial», BJOG, 2000 Apr, 107(4), pp. 524-530. 86. WHO, «Task Force on Post-ovulatory Methods for Fertility Regulation. Lowering the doses of mifepristone and gameprost for early abortion: a randomised controlled trial», BJOG, 2001 Jul, 108(7), pp. 738-742. 87. WHO, «World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial», BJOG, 2000 Apr, 107(4), pp. 524-530. 88. L. Say, «Medical versus surgical termination of pregnancy», Department of reproductive health and research, WHO, Aug 2000. 89. WHO, «Task Force on Post-ovulatory Methods of Fertility Regulation. Medical abortion at 57 to 63 days' gestation with a lower dose of mifepristone and gemeprost. A randomized controlled trial», Acta Obstet Gynecol Scand, 2001, 80(5), pp. 447-451. 90. WHO, «Task Force on Post-ovulatory Methods for Fertility Regulation. Lowering the doses of mifepristone and gemeprost for early abortion: a randomised controlled trial», BJOG, 2001 Jul, 108(7), pp. 738-742. 91. ACOG Practice Bulletin, «Clinical management guidelines for obstetrician-gynecologists. Medical management of abortion», Obstet Gynecol, 2001 Apr, 97(4), suppl 1-13. 92. RCOG guidelines, The care of women requesting induced abortion, Guideline No 7. Rgog bookshop. 2000. 93. ANAES Guidelines Department. Induced abortion up to 14 weeks. English version. Marzo 2001.

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ce, per l'aborto con mifepristone e misoprostolo fino a 56 giorni e nel secondo trimestre e per quello del secondo trimestre. Lo stesso fa il RCOG, secondo lo schema per i livelli di evidenza raccomandato dal NHS Executive, dando il grado A e B per l'aborto medico con il mifepristone in tutte le epoche gestazionali, ritenendo appropriata una dose di 200 mg. L'ANAES, per conto della Direction Génerale de Santé, attribuisce un grado A di evidenza all'aborto medico fino a 49 giorni sia in ospedale che a casa, e anche per quello tra 50 e 63 giorni con la prescrizione che dovrebbe svolgersi in un ambiente ospedaliero. Il protocollo prevede la somministrazione del mifepristone, seguita due giorni dopo da quella orale o vaginale di una prostaglandina, ma si è osservato che il risultato è sovrapponibile se la somministrazione avviene da uno a tre giorni dopo.94 A tale scopo la prostaglandina più usata è il misoprostol, disponibile a basso costo in compresse termostabili e somministrata per via orale o endovaginale, sebbene alcuni autori preferiscono utilizzare il gemeprost, più costoso e disponibile in candelette vaginali da conservare in frigorifero. Il mifepristone e il misoprostol sono farmaci con altre indicazioni mediche. Il misoprostol, registrato come un antiulcera in più di 70 paesi, può essere utilizzato per indurre un travaglio abortivo nel primo e nel secondo trimestre, per indurre un travaglio di parto a termine con feto vivo o morto, completare un aborto incompleto, preparare la cervice per l'aborto chirurgico e trattare un'emorragia post partum. Gli effetti collaterali sono generalmente minori di quelli delle altre prostaglandine, dipendono dalla dose, sembrano diminuire con la via vaginale e aumentano con l'epoca gestazionale. Sono state sperimentate anche le vie sublinguale95,96 e rettale.97 In Italia il costo al dettaglio di una compressa di misoprostol da 200 mcg è di circa 0,33 euro. Il mifepristone è registrato anche per preparare l'aborto chirurgico, per accelerare l'aborto nel secondo trimestre e per favorire l'espulsione di

94. E. A. Schaff, S. L. Fielding, C. Westhoff, C. Ellertson, S. H. Eisinger, L. S. Stadalius, L. Fuler, «Vaginal misoprostol administered 1-3 days after mifepristone for early medical abortion: a randomized trial», JAMA, 2000, 284, pp. 1948-1953. 95. P T. Wagaarachchi, P W. Ashok, N. C. Smith, A. Templeton, «Medical management of early . . fetal demise using sublingual misoprostrol», Br J Obstet Gynaecol, 2002 apr, 109(4), pp. 462-465. 96. «Pilot study on the use of sublingual misoprostol with mifepristone in termination of first trimester pregnancy up to 9 weeks gestation», Hum Reprod, 2002, 17(7), pp. 1738-1740. 97. A. A. Bamigboye, G. J. Hofmeyr, D. A. Merrell, «Rectal misoprostol in the prevention of postpartum hemorrhage: a placebo-controlled trial», Am J Obstet Gynecol, 1998, 179, pp. 1043-1046.

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un feto morto. Vi sono poi altre indicazioni ostetriche, come l'aborto interno, l'aborto incompleto, il trattamento medico delle gravidanze extrauterine e l'induzione del travaglio di parto con feto vivo. A basse dosi è efficace come contraccettivo di emergenza. Sono però sempre più interessanti le indicazioni in campo medico e oncologico, che sfruttano le caratteristiche ormonali per il trattamento dei leiomiomi uterini, dell'endometriosi, del meningioma, della sindrome di Cushing, della depressione e dei tumori della prostata, dell'ovaio, dell'endometrio e della mammella. In alcuni casi, come nel meningiona, nella depressione, nei fibromiomi e in tutte quelle situazioni dove è utile un potente antiprogestinico-antiglucorticoide, si è gia nella fase di sperimentazione clinica. In Europa il costo al dettaglio di una compressa di 200 mg di mifepristone è di circa 20 euro.

Meccanismo dell'aborto

Il mifepristone promuove un'azione di down-regulation, compromettendo i vasi endometriali, aumentando l'eccitabilità delle cellule endometriali e dilatando la cervice, con conseguente necrosi deciduale e possibile distacco del prodotto del concepimento. Prepara il terreno alla prostaglandina, che viene somministrata 36-48 ore dopo e favorisce l'espulsione dell'embrione, la cui dimensione a 6-7 settimane e circa un centimetro, e della mucosa, provocando una emorragia mestruale abbondante. Dopo l'assunzione per via orale del mifepristone il 30-50 per cento delle donne potrà avere delle perdite ematiche, ma un aborto si verificherà solo nel 2-3 per cento dei casi. L'espulsione avviene dopo la somministrazione per via orale del misoprostol, entro 3-4 ore nel 50-60 per cento dei casi, entro 24 ore nel 20 per cento, e successivamente nel 10 per cento, mentre in un 10 per cento rimane indeterminato98,99 Una seconda dose di misoprostol dopo 3 ore aumenta la percentuale di successo al 98,5 per cento.100 Circa il 2-5 per cento delle donne avrà una revisione della cavità uterina per sanguinamento eccessivo o per il persistere in utero di materiale

98. E. Aubèny, R. Peyron, C. L. Turpin, M. Renault, V Targosz, L. Silvestre, et al., «Termination . of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol», Int J Fertil Menopausal Stud, 1995, 40, Suppl 2, pp. 85-91. 99. R. Peyron, E. Aubèny,V Targosz, L. Silvestre, M. Renault, F. Elkik, et al., «Early termination . of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol», N engl J Med, 1993 May, 328, pp. 1509-1513. 100. A. Bureau, I. Dagousset, «IVG medicamentouse: possible chez la plupart des femmes», Rev Prat Med Gen, 2000 Sep, 14(506), pp. 1377-1381. French.

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ovulare, nei giorni successivi o alla visita di controllo 10 giorni dopo. In una metanalisi si è visto che la percentuale di aborti incompleti, fino a 49 giorni, è del 3,6 per cento, mentre le gravidanze che proseguono sono l'uno per cento, che con una seconda dose di prostaglandina queste percentuali si riducono all'1,8 e allo 0,9 per cento e che i tassi di insuccesso raddoppiano a 50-56 giorni e triplicano 57-63 giorni.101 In pratica con l'aborto medico viene provocato un aborto spontaneo, nel senso che la dinamica e il corteo sintomatologico sono indistinguibili da quelli di un aborto spontaneo. Si tratta in pratica di un flusso mestruale percepito come più abbondante con perdita di «coaguli», che persiste più a lungo, più doloroso nelle fasi culminanti che precedono l'espulsione. Negli aborti fino a 49 giorni non si vede l'embrione, al massimo si percepisce un agglomerato di mucosa gravidica.

Effetti colaterali, complicazioni e controindicazioni

A parte il fallimento completo, o parziale, dell'aborto medico, che è una complicazione, perché espone la donna a quella revisione della cavità uterina che voleva evitare, gli effetti collaterali e le complicazioni sono minori di quelle dell'aborto chirurgico e di quelle che la donna potrebbe andare potenzialmente incontro con il proseguimento della gravidanza. Infatti la mortalità e la morbosità per la gravidanza sono almeno dieci volte maggiori a quelle dell'aborto, anche dove l'aborto è illegale. Questa considerazione è necessaria perché l'argomentazione di un maggiore rischio per la salute della donna è uno degli argomenti che si tenta di utilizzare, quando il fronte antiabortista si avventura in argomentazioni mediche. Negli Stati Uniti un ricorso alla FDA di tre gruppi pro-life, la Concerned Women for America, la Christian Medical Association e la American Association of Pro-Life Obstetricians and Gynecologist, non ha avuto seguito.102 Nel complesso gli effetti collaterali non implicano grosse problematiche, le complicazioni sono scarse e, a parte le perdite ematiche, dipendono dalle prostaglandine. Le perdite ematiche durano 9-10 giorni (limiti 1-32 giorni), ma possono prolungarsi in modo ridotto anche fino al successivo flusso mestruale. Di solito non necessitano di alcun trattamento,100 il rischio di una tra101. J. G. Kahn, B. J. Becker, L. MacIsaac, et al., «The efficacy of medical abortion: a metaanalysis», Contraception, 2000, 61, pp. 29-40. 102. «Washington in Brief: groups urge abortion pill withdrawn», Washington Post, 22 agosto 2002.

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sfusione è 0,1-0,2 per cento103 e non è riportato alcun intervento di isterectomia. Uno studio su oltre 4.000 casi ha concluso che il rischio di un curettage è basso, 2,6 per cento, distribuito nel tempo come conseguenza del persistere delle perdite ematiche, essendo il rischio di un sanguinamento acuto estremamente raro.104 In due studi comparativi tra aborto medico e chirurgico è stato osservato come, nonostante il più lungo periodo di sanguinamento e una differente percezione soggettiva, non vi siano differenze tra gli indicatori clinici dei due gruppi e raramente avvengano cambiamenti significativi nel valore dell'emoglobina.105,106 Nello storico trial francese la riduzione dell'emoglobina fu di 2 g/dl nel 6 per cento dei casi,98 una quantità che di norma non viene considerata preoccupante in medicina. Il dolore, crampiforme, accompagna il periodo espulsivo, aumenta con l'epoca gestazionale, è abbastanza sensibile agli analgesici, e varia moltissimo in relazione alla tolleranza e alle esperienze personali. In letteratura l'uso di analgesici è riportato dallo 0 al 73 per cento con una media del 27 per cento.74,107 Negli Stati Uniti è riportato l'uso dell'ipobrufene e dell'acetomifene, quest'ultimo in associazione con oppioidi minori,103 in Francia una associazione paracetamolo-oppioide-belladonna e nell'1-2 per cento un'iniezione di nefopan,100 in Gran Bretagna un'associazione paracetamolocodeina e in una buona percentuale di casi la morfina.108 Sembra che il bisogno di analgesia sia minore per l'aborto chirurgico, dal 2 al 37 per cento, nonostante il dolore sia costante, ma probabilmente è più accettabile, perché collegato a un momento considerato concluso, mentre nell'aborto medico l'evoluzione dell'aborto è più indefinita. In ogni caso il dolore è gestibile perfettamente con antidolorifici. Sintomi gastrointestinali sono presenti in quasi la metà delle donne,

103. B. Kruse, S. Poppema, M. D. Creinin, M. Paul, «Maagement of side effects and complications in medical abortion», Am J Obstet Gynecol, 2000 (2 suppl), 183, pp. S65-S75. 104. R. H. Allen, C. Westhoff, L. De Nono, S. L. Fielding, E. A. Schaff, «Curettage after mifepristone-induced abortion: frequency, timinh and indications», Obstet Gynecol, 2001, 98, pp. 101-106. 105. J. T. Jensen, S. M. Harvey, L. J. Beckman, «Acceptability of suction curettage and mifepristone abortion in the United States: a prospective comparison study», Am J Obstet Gynecol, 2000 Jun, 182(6), pp. 1292-1299. 106. C. Harper, B. Winikoff, C. Ellertson, K. Coyaji, «Blood loss with mifepristone-misoprostol abortion: measures fron a trial in China, Cuba and india», Int J Gynecol Obstet, 1998, 63, pp. 39-49. 107. C. Westhoff, R. Dasmahapatra, B. Winifoff, S. Clarke and the Mifepristone Clinical Trials Group, «Predictors of analgesia use during supervised medical abortion», Contraception, 2000, 61, pp. 225-229. 108. P W. Ashok, A. Kidd, M. M. Flett, A. Fitzmaurice, W. Graham, A. Templeton, «A randomi. zed comparison of medical abortion and surgical vacuum aspiration at 10-13 weeks gestation», Hum Reprod, 2002, 17(1), pp. 92-98.

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dipendono dalla prostaglandina, sono autolimitanti e si risolvono senza bisogno di terapia. La nausea è il sintomo più frequente, presente nel 34-72 per cento dei casi, il vomito nel 12-41 per cento e la diarrea nel 3-26 per cento. Per la nausea e il vomito può essere necessario un trattamento nel 3 per cento dei casi, mentre per la diarrea non vi è alcun bisogno di trattamento.100 Altri sintomi transitori presenti in percentuali minime possono essere cefalea, vertigini e stanchezza. Un'elevazione della temperatura corporea, che non desta preoccupazione, è presente nel 4-37 per cento dei casi. L'endometrite è una complicazione limitata, più frequente nell'aborto chirurgico.164 Le vere controindicazioni sono poche ed elencate dal produttore: il sospetto di gravidanza extrauterina, una spirale in utero, un'insufficienza surrenalica cronica, un trattamento in corso da tempo con corticosteroidi, l'allergia al mifepristone, al misoprostol o verso altre prostaglandine, coagulopatie e trattamenti in corso con anticoagulanti. Una grave anemia (Hb < 7g/dl) suggerisce il trattamento chirurgico per la maggiore facilità di verifica dell'entità del sanguinamento.103 La gravidanza extrauterina deve essere esclusa prima della somministrazione del misoprostol. Una spirale deve essere rimossa prima del trattamento. Occorre tenere presente che il mifepristone riduce l'efficacia della terapia con corticosteroidi, che la rifampicina, il desametazone e gli anticonvulsivanti possono accelerare il metabolismo del mifepristone, riducendone l'efficacia, che è meglio non assumere acido acetilsalicico nei giorni precedenti e successivamente.109 Inoltre l'uso delle prostaglandine deve indurre a valutare la presenza di patologie cardiovascolari di natura ischemica. Il fumo non è una controindicazione, ma le donne di età superiore a 35 anni, che fumano più di 10 sigarette sono state generalmente escluse dai trial clinici. Si tratta di una misura eccessivamente prudenziale, che non è rispettata per le interruzioni del secondo trimestre, eseguite con dosi ben maggiori di prostaglandine. La donna deve essere informata della teratogenicità del misoprostol nel primo trimestre;110 il rischio di malformazioni è certamente sovrastimato, per cui non è indicata la sistematica interruzione della gravidanza se

109. Note informative allegate alla confezione di Mifegyne®, approvate dall'autorità sanitaria francese il 15 dicembre 1999. 110. In Brasile e in America centrale, dove il misoprostol è ampiamente utilizzato come abortivo, sono state osservate che i bambini la sindrome di Möbius (paralisi congenita del sesto nervo cranico e di altri nervi cranici) e una frequenza superiore all'attesa di idrocefalia, oloprosencefalia, estrofia della vescica, briglie amniotiche, difetti di riduzione terminale traversa degli arti e artrogriposi.

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la donna non vuole più interrompere la gravidanza dopo un fallimento.100 Il mifepristone invece non è teratogeno, per cui se la donna cambia idea dopo la sua assunzione e la gravidanza dovesse proseguire non vi sarebbe un rischio aggiuntivo di malformazioni, oltre quello normale di ogni gravidanza.

Accettabilità

Si tratta di un metodo che impegna attivamente la donna per alcuni giorni, anche se la fase espulsiva si risolve in poche ore nella maggioranza dei casi, e che la responsabilizza maggiormente, perché è lei che compie il gesto abortivo, che ne controlla il decorso dell'aborto e che può vedere il materiale espulso. Nonostante questo in tutti gli studi l'80-90 per cento delle donne lo sceglierebbe ancora e quando possono scegliere la maggioranza lo preferisce. In uno studio la durata delle perdite ematiche è stata maggiore di quella attesa nel 42 per cento, come la quantità 37 per cento, mentre il dolore lo è stato nel 20 per cento, con valori simili sia nel gruppo che ha abortito, che in quello che ha fallito. Ma l'esperienza complessiva veniva giudicata peggiore di quella attesa solo dal 12 per cento delle donne che avevano abortito con successo, e non andava oltre il 45 per cento tra le donne che invece avevano incontrato un fallimento.111 In realtà l'indice di soddisfazione è sempre alto sia per l'aborto medico che per quello chirurgico112 e, per entrambi i metodi, la percentuale di donne che lo raccomanderebbe a una amica è sempre alta. Questo probabilmente perché la maggioranza delle donne si sente comunque sollevata dopo l'aborto. Tutto ciò dimostra che entrambi sono metodi accettati e che la scelta del metodo dipende dalle informazioni ricevute e dal profilo della donna.113 Emergono infatti due profili significativamente diversi di donne. Quelle che scelgono l'aborto chirurgico sottolineano la velocità del metodo e la necessità di un numero minore di visite, temono i sintomi dell'aborto medico, preferiscono sapere esattamente quando l'aborto avviene e sono rassicurate dal delegare al medico l'esecuzione. Quelle che invece scelgono l'aborto medico danno molta importanza al fatto di evitare

111. B. Winikoff, C. Ellertson, B. Elul, I. Sivin, «Acceptability and feasibility of early pregnancy termination by mifepristone-misoprostol. Results of a large multicenter trial in the United States. Mifepristone Clinical Trials Group», Arch Fam Med, 1998, 7, pp. 360-366. 112. C. Westhoff, L. Picardo, E. Morow, «Quality of life following early medical o surgical abortion», Contraception, 2003, 67, pp. 41-47 113. S. M. Harvey, L. J. Beckman, S. J. Satre, «Choice of and satisfaction with methods of medical and surgical abortion among U.S. clinic patients», Fam Plann Perspect, 2001 SepOct, 33(5), pp. 212-216.

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l'intervento chirurgico, sono soddisfatte che l'aborto avvenga in modo più naturale e lo considerano più intimo, accettando di essere coinvolte. In entrambi i gruppi un 20 per cento sceglie il metodo, medico o chirurgico, perché lo considera meno doloroso. Dove l'aborto medico è realmente offerto, la percentuale di donne che sceglie l'aborto medico è in crescita; nella cattolica Scozia è il 61 per cento, in Francia il 56 per cento e in Svezia il 51 per cento. In Inghilterra è solo l'8 per cento, ma il Ministero della sanità ha deciso di promuoverlo, autorizzandolo anche nei centri territoriali.

Un imperativo etico

Sul piano politico quella per il mifepristone è una battaglia di civiltà, sul piano medico è un imperativo etico. Con il mifepristone l'interruzione della gravidanza può avvenire più precocemente, riducendo i rischi di maggiori complicazioni successive ed evitando un'attesa spesso psicologicamente e fisicamente difficile. Il fatto che l'aborto avvenga prima di quanto accada oggi con l'aborto chirurgico permette di percepirlo come più accettabile e non vi è peraltro nessuna ragione, etica o medica, che giustifichi l'esposizione di una donna ai maggiori rischi di un aborto in epoca successiva. In altre parole l'anticipazione dell'aborto permette di considerarlo meno un aborto, poiché è naturale che il valore etico della gravidanza, dell'embrione o della vita sia percepito diversamente durante la sua evoluzione, sia da parte dei laici che dalle persone di fede religiosa. Se è comprensibile che la coscienza di ognuno ponga un limite cronologico assoluto (il concepimento, lo sviluppo del sistema nervoso, il primo trimestre, una qualsiasi settimana o la vitalità del feto) occorre prendere atto che vi è anche un valore relativo alle diverse situazioni evolutive della gravidanza. E' naturale quindi che a un «flusso» di materiale indefinito sia attribuito un valore etico diverso di quello di un embrione, o di un feto, di un'epoca successiva, più formato e più visibile, come è esperienza quotidiana vedere come la sacralità della vita si infranga nell'aborto di un feto Down nel secondo trimestre, nella soppressione di un gemello di una gravidanza plurigemellare o nella pietosa decisione di sopprimere una gravidanza con feto sofferente prima che superi il limite gestazionale che la legge consente.

114. H. von Hertzen, «Research on regimens for early medical abortion», J Am Med Womens Assoc, 2000, 55(3 Suppl), pp. 133-136, 150.

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Io, che non credo al concetto assoluto di vita embrionale, non ammazzo un handicappato dal momento cronologico in cui lo considero una persona, cosa che accade regolarmente da parte di chi considera l'embrione una persona, quando scopre la malformazione. Lo stesso vale per la citoriduzione embrio-fetale o per la presenza di una sofferenza fetale in periodo pre-vitale. Da queste considerazioni ne consegue l'obbligo morale di fornire tutte le possibilità di scelta per tutte le sensibilità etiche individuali e collettive, diventando irrilevante la disputa sui vantaggi del metodo medico o del metodo chirurgico, essendo entrambi ampiamente nei binari della compatibilità con la pratica medica. Le linee guida delle associazioni mediche, che si sono poste il problema, hanno sempre affermato la necessità di permettere la possibilità di scelta tra metodo medico e chirurgico ed è ora che la questione del mifepristone sia affrontata dalle associazioni professionali dei ginecologi e dei medici italiani sotto il profilo etico, scientifico e professionale. Vi è poi l'aspetto, non meno importante, che è la donna stessa ad assumere il farmaco, sotto la supervisione medica, ma è lei che compie consapevolmente l'atto abortivo, senza delegarlo a un altro. E' un'assunzione di responsabilità piena e consapevole da parte della donna, che è l'unica persona chiamata a decidere per se stessa, in quanto è colei che subisce le conseguenze dell'interruzione o del proseguimento della gravidanza, con tutte le possibili implicazioni mediche, psicologiche e sociali. Trasformare il medico in semplice supervisore può favorire un impegno di molti medici che non vogliono eseguire direttamente l'atto abortivo, per cui l'introduzione di un metodo clinicamente meno impegnativo e potenzialmente extraospedaliero può permettere una più diffusa e omogenea applicazione territoriale della 194, ma non sono questi gli aspetti principali e non sarà certo la RU 486 che risolverà le questioni aperte sull'obiezione di coscienza. Proprio la tutela «dell'obiezione di coscienza in rapporto alle pratiche abortive» è stata ampiamente trattata da Medicina e morale, ponendo la questione delle «fasi successive all'assunzione del mifepristone e del misoprostolo senza che ancora si sia realizzata l'espulsione dell'embrione», «prima del completo effetto abortivo». Tralasciando ogni considerazione sulle conseguenze di un'obiezione di coscienza di tipo premiale, è chiaro che tale legittima preoccupazione non è affatto una controindicazione all'introduzione del metodo. Il medico obiettore, come nei confronti dell'assistenza di chi tenta un aborto illegale, dovrà semplicemente assumersi le proprie responsabilità deontologiche e legali, valutando la fase del procedimento abortivo, il qua-

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dro clinico della paziente e la sopravvenuta interruzione della gravidanza. A tale proposito l'avvenuta interruzione della gravidanza, con l'inizio della fase della «assistenza conseguente», non coincide con l'espulsione del prodotto abortivo, difficilmente individuabile, ma viene diagnosticata con la constatazione di un quadro clinico di aborto interno, di aborto in atto o di aborto inevitabile, la diagnosi deve essere fatta mediante la visita ginecologica, la valutazione delle perdite ematiche e l'esecuzione di un'ecografia, non potendo rifiutarsi di fornire una prestazione diagnostica, per la presunzione di una gravidanza in evoluzione con attività cardiaca presente. Se la questione dell'obiezione di coscienza, specificamente considerata dal progetto di sperimentazione del S. Anna, non è un ostacolo per l'introduzione dell'aborto medico, le altre obiezioni sollevate sono considerabili dei pretesti per una obiezione politica. Un pretesto è la questione della pericolosità del mifepristone: non superiore a quella dell'intervento chirurgico e i cui potenziali rischi extraospedalieri sono minori a quelli di molti condizioni in cui i pazienti sono dimessi a domicilio dopo un intervento chirurgico o gravi condizioni patologiche. Un pretesto è anche la questione del «presso», le cui problematiche interpretative sembrano essere sollevate ad arte per prendere tempo e indurre il Comitato etico piemontese a ritardare la conclusione degli ultimi adempimenti. La questione dei costi è paradossale. Il punto è che in Italia il mifepristone è solo l'ultimo tabù. Si può reagire, come propone Medicina e morale, sostenendo che non si dovrebbe «rendere l'aborto più facile, quanto impegnarsi a favore della vita, cercando di offrire valide alternative a una scelta, l'aborto, che causa la morte di migliaia di individui umani e determina persistenti danni psicologici alla donna». Oppure si può ribadire, che l'aborto è un intervento sanitario, che deve essere eseguito nel modo più semplice e sicuro, che deve essere rispettato il diritto della donna di scegliere, compreso quello di potere valutare le possibili alternative, ma che l'intervento deve essere garantito anche il giorno in cui il 100 per cento dei medici fosse obiettore, e che ogni opinione sul significato dell'embrione non può essere imposta per legge, non esistendo più una religione di stato. Si deve avere il coraggio di aiutare le donne sostenendole, se lo desiderano, durante tutto il percorso e anche dopo, perché se è vero che una minima parte può avere problemi di rimorso, la stragrande maggioranza supera l'evento con normali meccanismi di reazione psicologica e comportamentale. La cosiddetta «sindrome post-aborto», esclusivamente osservata nei circoli antiabortisti, è comunque di gran lunga meno diffusa della «sindro-

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me depressiva post-parto», per scongiurare la quale nessuno si è mai sognato di vietare la gravidanza. Non bisogna temere di ricordare che la disponibilità legale dell'aborto, l'incremento dei metodi contraccettivi, la disponibilità della contraccezione di emergenza (senza prescrizione medica), l'educazione sessuale e riproduttiva sin dall'adolescenza sono tanti tasselli di un percorso di prevenzione primaria per rendere la donna più libera e più consapevole delle proprie scelte. Vi è l'imperativo etico di rompere questo ultimo tabù per recuperare un ritardo decennale nella registrazione del mifepristone, commercializzato come Mifegyne dall'Exelgyn di Parigi.

BIOETICA 3/2003 549

GUIDELINE

Royal College of Obstetricians and Gynaecologists

Setting standards to improve women's health

The Care of Women Requesting Induced Abortion

Evidence-based Clinical Guideline Number 7

September 2004

The Care of Women Requesting Induced Abortion

Evidence-based Clinical Guideline Number 7

September 2004

Royal College of Obstetricians and Gynaecologists

Setting standards to improve women's health

First published 2000 This revision published September 2004 © Royal College of Obstetricians and Gynaecologists 2004 ISBN 1-904752-06-3 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the Publisher (Royal College of Obstetricians and Gynaecologists). The RCOG consents to the copying of this guideline for the purpose of producing local protocols/guidelines in the United Kingdom, provided that RCOG is cited as the source. The use of registered names, trademarks etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulation and therefore free for general use. Product liability: the RCOG can give no guarantee for information about drug dosage and application thereof contained in this guideline. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.`

Published by the RCOG Press at the Royal College of Obstetricians and Gynaecologists Registered Charity No. 213280

Copies of the Guideline Summary and a version for women and their families can be obtained from the website at www.rcog.org.uk All correspondence with regard to this guideline should be addressed to: Clinical Governance and Standards Department Royal College of Obstetricians and Gynaecologists 27 Sussex Place Regent's Park London NW1 4RG Telephone: +44 (0) 20 7772 6369 Email: [email protected] Website: www.rcog.org.uk

Design and setting by FiSH Books, London. Printed by Manor Press, Unit 1, Priors Way, Maidenhead, Berks. SL6 2EL

Contents

Abbreviations Development of the guideline Peer reviewers Acknowledgements v vii viii viii

1.

Introduction and methodology 1.1 The guideline topic 1.2 Aim of the guideline 1.3 For whom is this guideline intended? 1.4 Local protocol development 1.5 Methods used in the development of this guideline 1.6 Implementation and review Summary of recommendations 2.1 Organisation of services 2.2 Information for women 2.3 Pre-abortion management 2.4 Abortion procedures 2.5 Aftercare Legal and ethical aspects of abortion 3.1 The Abortion Act 3.2 Good professional practice 3.3 Confidentiality 3.4 Professionals' rights: conscientious objection to abortion 3.5 Issues relating to consent to treatment 3.6 Abuse of children and vulnerable people 3.7 Rights of the spouse or partner 3.8 Disposal of fetal tissue Organisation of services 4.1 Access and referral to abortion services 4.2 Waiting times in abortion services 4.3 Settings for abortion care Information for women Pre-abortion management 6.1 The abortion decision 6.2 Blood tests

1 1 3 3 4 4 6 7 7 8 9 10 13 14 14 16 16 16 17 19 20 20 22 22 23 24 28 36 36 37

2.

3.

4.

5. 6.

The Care of Women Requesting Induced Abortion

6.3 6.4 6.5 6.6 7. Cervical cytology Ultrasound scanning Prevention of infective complications Feticide prior to late abortions 38 39 40 43 44 45 51 56 57 59 59 60 60 63 63 63 63 63 64 65 65 66 66 66 67 68 69 70 70 71 74 76 78 80 86 87 101

Abortion procedures 7.1 Surgical methods of abortion 7.2 Medical methods of abortion 7.3 Analgesia for abortion care 7.4 Histopathology Aftercare 8.1 Rhesus prophylaxis 8.2 Post-abortion information and follow-up 8.3 Contraception following abortion Standards for audit and service accreditation 9.1 Organisation of services 9.2 Information for women 9.3 Pre-abortion management 9.4 Abortion procedures 9.5 Aftercare

8.

9.

Appendix: Evidence tables 1 Relative safety of abortion at increasing gestations 2 Rate of uterine perforation during termination of pregnancy 3 Incidence of cervical injury during first-trimester abortion by vacuum aspiration 4 Incidence of cervical injury during second-trimester abortion by dilatation and evacuation in illustrative large case series 5 Induced abortion and subsequent breast cancer risk 6 Future reproductive outcomes 7 Induced abortion and subsequent mental health 8 Studies relating to local versus general anaesthesia 9 Studies comparing manual with electric vacuum aspiration 10 Cervical priming randomised controlled trials 11 Cervical priming prior to surgical abortion 12 Combined early medical abortion regimens 13 Comparisons of regimens used in first-trimester abortions 14 Studies comparing various agents used in second-trimester medical abortions 15 Use of oxytocic agents to reduce blood loss at the time of surgical abortion References Index

iv

Abbreviations

ACOG hCG BMA bpas CEMD CI CMO COC COG D&C D&E DARE DH DSH EP FFPRHC FHPM FIGO fpa GMC GP GUM hCG HFEA HIV HTA IUD IUS KCl MDU MVA NCI NCSC NHS NMC NSAID OR OOR PCO PID American College of Obstetricians and Gynecologists beta human chorionic gonadotrophin British Medical Association British Pregnancy Advisory Service Confidential Enquiries into Maternal Deaths in the UK confidence interval Chief Medical Officer combined oral contraceptive Clinical Outcomes group dilatation and curettage dilatation and evacuation Cochrane Library Database of Reviews of Effectiveness Department of Health deliberate self harm ectopic pregnancy Faculty of Family Planning and Reproductive Health Care Faculty of Public Health Medicine International Federation of Gynecology and Obstetrics Family Planning Association General Medical Council general practitioner genitourinary medicine human chorionic gonadotrophin Human Fertilisation and Embryology Authority human immunodeficiency virus Health Technology Assessment intrauterine device intrauterine system potassium chloride Medical Defence Union manual vacuum aspiration National Cancer Institute National Care Standards Commission National Health Service Nursing and Midwifery Council nonsteroidal anti-inflammatory drug odds ratio overall odds ratio primary care organisation pelvic inflammatory disease

v

The Care of Women Requesting Induced Abortion

POP RCN RCOG RCT Rh RR UKCC VAS WHO WHOMEC progestogen-only pill Royal College of Nursing Royal College of Obstetricians and Gynaecologists randomised controlled trial rhesus relative risk United Kingdom Central Council for Nursing, Midwifery and Health Visiting visual analogue scale World Health Organization World Health Organization medical eligibility criteria

vi

Development of the guideline

This guideline on abortion care was first developed in 2000 by a multi-professional working group (referred to here as the Guideline Development Group). The group was convened by the Royal College of Obstetricians and Gynaecologists (RCOG) and supported by funding awarded by the Department of Health (DH). Members included nominees of the RCOG, the Faculty of Family Planning and Reproductive Health Care (FFPRHC), the Royal College of General Practitioners, the Faculty of Public Health, the British Pregnancy Advisory Service (bpas), a nurse counsellor and a consumer representative nominated by the RCOG Consumers' Forum. All members of the group made formal declarations of interest at the outset and these were recorded. This record is kept on file at the RCOG. The College was of the opinion that the interests declared did not conflict with the guideline development process. The development of this updated version of the guideline was led by Dr Gillian Penney FRCOG, who chaired the Guideline Development Group and is Honorary Director of the Clinical Effectiveness Unit of the FFPRHC. Funding was again provided by the Department of Health. The development process incorporated a single meeting of an expert advisory group (referred to here as the Guideline Update Group) in December 2003. The members were: Dr Gillian Penney (Chair), Scottish Programme for Clinical Effectiveness in Reproductive Health, RCOG nominee. Dr Susan Brechin, FFPRHC Clinical Effectiveness Unit Dr Ken Bidgood, RCOG nominee Ms Ann Furedi, bpas, charitable sector representative Mrs Susie Marwood, RCOG Consumers' Forum representative Dr Kate Guthrie, FFPRHC nominee Dr Sharon Hopkins, Faculty of Public Health Medicine nominee Dr Hilary McDermott, Royal College of General Practitioners nominee Ms Hazel McBain, Nurse Counsellor Mr Sam Mirando, FFPRHC nominee Mr Anthony Parsons, RCOG nominee Dr Connie Smith, FFPRHC nominee Dr Sam Rowlands, bpas, charitable sector representative Dr Helen Ribbans, FFPRHC nominee Mr Michael Bowen, Department of Health observer Miss Gillian Stephen, Research Assistant

vii

The Care of Women Requesting Induced Abortion

The development of this updated guideline was supported by the RCOG Guidelines and Audit Committee. The members were: Miss MC Davies MRCOG (Chair) Dr RA Anderson MRCOG Ms T Belfield (Consumer's Forum representative), Family Planning Association Mrs C Dhillon, Head of Clinical Governance and Standards, RCOG Miss K Duckitt MRCOG Miss LMM Duley FRCOG Professor NM Fisk FRCOG, Chairman of the RCOG Scientific Advisory Committee Mr JM Jenkins FRCOG Professor WL Ledger FRCOG Dr G Lewis FRCOG, Department of Health Dr MCM Macintosh MRCOG, Confidential Enquiries into Maternal and Child Health Dr D Rajasingam MRCOG (Trainees' representative) Ms W Riches, National Institute for Clinical Excellence observer Mr IV Scott FRCOG Mr MI Shafi MRCOG Mr CR Stewart FRCOG, co-opted member Miss JM Thomas MRCOG, National Collaborating Centre for Women's and Children's Health

Peer reviewers

Comments were received from the following individuals during the peer review stage. A summary table of comments received and actions taken is available on request from the RCOG. Sheila Adam Vincent Argent Lucy Caird Kay Ellis Kathy French Sunanda Gupta Lesz Lancucki CJ McNicholas Victoria Pickles

Acknowledgements

The Guideline Update Group and the Guidelines and Audit Committee would like to thank Gill Roberts, Writer/Editor, RCOG Clinical Governance and Standards Department, and Elaine Garrett, RCOG Reader Services Librarian, for their assistance with this revision.

viii

Chapter 1

Introduction and methodology

1.1 The guideline topic

Induced abortion is one of the most commonly performed gynaecological procedures in Great Britain, with around 186 000 terminations performed annually in England and Wales1 and around 11 500 in Scotland.2 The Abortion Act does not apply in Northern Ireland and no official abortion statistics are collected. At least one-third of British women will have had an abortion by the time they reach the age of 45 years.3 Over 98% of induced abortions in Britain are undertaken because of risk to the mental or physical health of the woman or her children.1,2 This guideline has been developed in relation to the care of women seeking abortion on such grounds. Separate RCOG publications address legal, ethical and service issues relating to the minority of abortions undertaken because of fetal abnormality.4,5,6 The recommendations in this guideline do not address the special issues relating to abortion for fetal abnormality.

97 78

97 88 77

99.8

Highest PCO 46 Lowest PCO % overall NHS

ENGLAND

WALES

SCOTLAND

Figure 1.1 Range of NHS-funded abortion provision among individual PCOs in England and Wales, and in Scotland; for each country, the bars show the percentage of abortions which are NHS-funded. Primary Care Organisations (PCOs) with the highest, mean and lowest levels of provision are shown (data for England and Wales from Abortion Statistics.1 Scottish data not routinely published at PCO-equivalent level)2

1

The Care of Women Requesting Induced Abortion

There are large geographical variations in access to NHS-funded abortion. In Scotland in 2002, 99.8% of abortions took place in NHS hospitals.2 In England and Wales in 2002, of a total of 175 569 abortions for residents of England and Wales, 73 053 (42%) took place in NHS hospitals, 64 045 (36%) were funded by the NHS under agency arrangements with charitable sector providers, and 38 471 (22%) were obtained privately.1 In England in 2002, women resident in 83 of 304 (27%) primary care organisations (PCO) had less than 75% of their abortions NHS-funded.1 Figure 1.1 summarises 2002 figures on levels of NHS-funded abortion provision among individual primary care organisations. Gestation at abortion represents an indicator of accessibility and responsiveness of services. Figure 1.2 summarises the proportions of all abortions performed in different gestation bands for England, Wales and Scotland. Because of these varying arrangements for provision, the clinical management of women requesting abortion spans a number of care sectors and involves a range of professionals. Abortion care was therefore considered by the RCOG to be a particularly appropriate topic for multidisciplinary guideline development. The groups which have developed this guideline view induced abortion as a healthcare need and reiterate the recommendation of the RCOG Working Party on Unplanned Pregnancy (1991)7 that "health authorities should accept responsibility for the abortions needed by women resident in their districts". Although this guideline addresses the discrete topic of abortion care, the guideline developers strongly support the concept that abortion care should be provided as an integral part of broader sexual health services.

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% ENGLAND WALES SCOTLAND

20 + 14­19 13­19 10­13 10­12 < 10 weeks

Figure 1.2 Proportion of legal abortions carried out in different gestation bands, 2002

2

Introduction and methodology

In 2001, the Department of Health published The National Strategy for Sexual Health and HIV.8 This document highlighted inequalities in access to abortion and reiterated the waiting time targets included within the 2000 edition of this guideline. The RCOG is encouraged by the fact that "addressing the disparities that exist in abortion services" is listed among the targets for the strategy. The provision of abortion as an integral part of broader sexual health services is reflected in the proposal within the strategy to "develop managed networks for sexual health services with a broader role for those working in primary care settings and with providers collaborating to plan services jointly so that they deliver a more comprehensive service to patients".8 Sexual health strategies developed by the National Assembly of Wales and by the Scottish Executive include similar targets for abortion care. In 1999, the International Federation of Gynecology and Obstetrics (FIGO) published eight recommendations regarding induced abortion for `non-medical' reasons. The summary recommendation was that "after appropriate counselling, a woman has the right to have access to medical or surgical induced abortion, and that healthcare services have an obligation to provide such services as safely as possible".9 In 2003, the World Health Organization (WHO) published Technical and Policy Guidance on Safe Abortion10 to assist health systems in making legal abortion safe and accessible. Again, the RCOG is encouraged by the support voiced by FIGO and WHO for the concept of safe abortion care. Unwanted pregnancies occur because women are unable to regulate their fertility by contraception alone. The complexities of managing sexual behaviour and the fallibility of contraception mean that some unwanted pregnancies are inevitable. The causes of unwanted pregnancies and the reasons why legal abortion remains a healthcare need were clearly summarised by the Birth Control Trust in their document, Abortion Provision in Britain,3 published to mark the 30th anniversary of the 1967 Abortion Act.

1.2 Aim of the guideline

Clinical guidelines have been defined as systematically developed statements which assist clinicians and patients in making decisions about appropriate treatment for specific conditions.11 The aim of this guideline is to ensure that all women considering induced abortion have access to a service of uniformly high quality. It is hoped that the guideline will be implemented across all relevant healthcare sectors and will promote a consistent standard, regardless of the sectors in which an individual woman is managed.

1.3 For whom is the guideline intended?

The guideline has been developed under the auspices of the RCOG for its Fellows and Members practising in the United Kingdom. The guideline may also be of interest to other professional groups who share in caring for women considering abortion: primary care teams, family planning clinic staff, gynaecology nurses, staff participating in non-NHS assessment centres and clinics, and all those professionals providing abortion counselling. Those with responsibilities for planning abortion services, for example directors of public health, NHS trust managers and managers of primary care groups, may also find the guideline helpful. In this guideline, the term `clinician' is used to refer to all healthcare professionals who participate in direct clinical patient care. Thus, the term includes doctors, nurses and midwives.

3

The Care of Women Requesting Induced Abortion

The guideline has been developed in relation to abortion legislation and available resources in England, Wales and Scotland. The different issues surrounding induced abortion in countries with different legislation and with different levels of resources and facilities are not considered.

1.4 Local protocol development

It is anticipated that this national guideline will be used as the basis for the development of local protocols or guidelines which will take into account local service provision and the needs and preferences of the local population. Such local adaptation should take place in a similar multidisciplinary group in consultation with all stakeholders affected by the recommendations. It is essential that commissioners of health care, as well as general practitioners, specialists and service users take part in such a process.12

1.5 Methods used in the development of the guideline

Literature search strategy

The aim of the literature review was to identify and synthesise relevant evidence within the published literature, thus enabling clinical practice recommendations to be based on evidence wherever possible. In developing the earlier version of this guideline in 2000, searches were carried out for each topic of interest. The electronic database, MEDLINE (Ovid version), was searched for the period January 1966 to 1999, including foreign language publications. The searches were performed using relevant MeSH (medical subject headings) terms and text words. In addition, the electronic database EMBASE was searched between 1974 to 1999, to identify publications, usually European, not indexed on MEDLINE. The Cochrane Library, up to Issue 2 (1999), was searched to identify systematic reviews, meta-analyses and controlled clinical trials. Reference lists of non-systematic review articles and studies obtained from the initial search were trawled and journals in the RCOG library were hand-searched to identify articles not yet indexed. There was no systematic attempt to search the `grey literature' (conferences, abstracts, theses and unpublished trials). In developing this edition, similar literature searches were carried out covering the period 1999 to September 2003. Details of all literature searches are available on application to the FFPRHC Clinical Effectiveness Unit. The 2000 guideline included a short section on managing the complications of abortion. The Guideline Update Group considered that this topic had been addressed somewhat superficially. It lay outwith the main scope of the guideline and would be better omitted. Recommendations on complications of abortion have therefore been restricted to those included in information for women (Chapter 5).

Sifting and reviewing the literature

For both the original and updating literature searches, a preliminary scrutiny of titles and abstracts was undertaken and full papers were obtained if they were relevant to the topic. Articles not relevant to the subject in question were rejected, as were articles where relevant outcomes were not reported. For all the subject areas, published systematic reviews or meta-analyses were used, if available. If these did not exist, randomised controlled trials were sought. For subject areas where

4

Introduction and methodology

a body of systematic review or randomised trial evidence was available, studies of less robust designs were not systematically sought. Where there were no relevant published randomised controlled trials, other appropriate experimental or observational studies were sought.

Synthesising the evidence

Identified articles were assessed methodologically and the best available evidence was used to form and support the recommendations. If a good systematic review, meta-analysis or randomised controlled trial existed in relation to a topic, studies of a weaker design were ignored. The evidence was synthesised using qualitative methods. These involved summarising the content of identified papers in the form of evidence tables and agreeing brief recommendation statements that accurately reflected the relevant evidence. Quantitative techniques (meta-analysis) were not performed by the guideline development team because of time constraints and the difficulty of combining studies of various designs.

Forming and grading the recommendations

The definitions of the types of evidence used in this guideline originate from the US Agency for Health Care Policy and Research (Table 1.1).13 Recommendations were based on, and explicitly linked to, the evidence that supports them. Recommendations were derived from available research evidence using consensus methods. Where there were areas without available research evidence, consensus was again used. As part of the consensus process, members of the Guideline Development Group were circulated with questionnaires on which draft recommendations were listed. For each recommendation, members were asked to indicate if they thought that the recommendation should be included as it stood, included with modifications or excluded. This questionnaire approach ensured that all group members, not just the more vocal, had an equal opportunity to express their views on recommendations. Examination of the questionnaire responses enabled the more contentious recommendations to be identified for more detailed discussion at subsequent group meetings. The Update Group used an informal consensus process to agree modified recommendations. The recommendations were then graded according to the level of evidence upon which they were based. The grading scheme used was formulated by the Clinical Outcomes Group and recommended by the NHS Executive.13 The strength of the evidence on which each recommendation is based is shown in Table 1.2. It is accepted that, in this grading system, the evidence itself is not graded according to quality, although

Table 1.1 Levels of evidence

Level Evidence Ia Ib IIa IIb III IV Evidence obtained from meta-analysis of randomised trials Evidence obtained from at least one randomised controlled trial Evidence obtained from at least one well-designed controlled study, without randomisation Evidence obtained from at least one other type of well-designed quasi-experimental study Evidence obtained from well designed non-experimental descriptive studies, correlation studies and case studies Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

5

The Care of Women Requesting Induced Abortion

Table 1.2 Forming recommendations

Grade of recommendation A B C Evidence level Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia, Ib) Requires the availability of well-conducted clinical studies, but no randomised clinical trials on the topic of the recommendation (evidence levels IIa, IIb, III) Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality (evidence level IV)

Good practice points Recommended best practice based on the clinical experience of the Guideline Development Groups

it is discussed narratively in the text supporting each recommendation. It is also accepted that randomised controlled trials may not always be the most appropriate study design (for example, to investigate diagnostic tests).13 Similarly, there may be clinical questions that cannot easily be answered by experiment but nevertheless represent good practice. Such recommendations will automatically be graded C or . The validity of some grade C and recommendations may be questionable, as they are not based upon incontrovertible evidence. However, the views of the 2000 Guideline and Update Groups combined with comments from extensive peer review, as detailed below, suggest that the recommendations with this grading are acceptable to a wide body of expert opinion.

Scope and methods of peer review

Successive drafts of the original guideline were written and discussed by the Guideline Development Group. At the fourth draft stage, a formal peer review process was undertaken. Each member of the group suggested names of individuals or organisations from the area of practice that they represented. The draft guideline was submitted to these individuals or organisations with a request for appraisal and comment. The comments made by the peer reviewers were taken into consideration by the Guideline Update Group before the final guideline was generated. Under the independent guideline appraisal system approved by the NHS Executive, the guideline was sent to a further group of reviewers who particularly concentrated on the methodology used in its development. For this edition, the second draft of the guideline was circulated for peer review to relevant individuals chosen by the Department of Health and the RCOG. The draft was also posted on the RCOG website and comments invited from any Member or Fellow. Comments received were reviewed by the development team and changes were made to the document where necessary. A final draft was then approved by the RCOG Guidelines and Audit Committee.

1.6 Implementation and review

This updated guideline was published in 2004. The RCOG will maintain a watching brief on the need to review recommendations in the light of new research evidence.

6

Chapter 2

Summary of recommendations

2.1 Organisation of services

1. Abortion services should have local strategies in place for providing information to both women and healthcare professionals on the choices available within the service and on routes of access to the service. Access to services should be ensured for women with special needs. For example, as appropriate, special arrangements should be made for non-English-speaking women and a woman doctor should be available. It is helpful if the referring doctor is able to provide the first signature on Certificate A. If a woman refers herself, or if the referring doctor is not willing to support the abortion, it must be possible for the woman to be assessed by a second doctor within the abortion service. Any woman considering induced abortion should have access to clinical assessment. Appropriate information and support should be available for those who consider but do not proceed to abortion. The earlier in pregnancy an abortion is performed, the lower the risk of complications. Services should therefore offer arrangements that minimise delay (for example, a telephone referral system and a formal care pathway with arrangements for access from a wide range of referral sources, not just general practitioners). Service arrangements should be such that: · ideally, all women requesting abortion are offered an assessment appointment within 5 days of referral. · as a minimum standard, all women requesting abortion are offered an assessment appointment within 2 weeks of referral. · ideally, all women can undergo the abortion within 7 days of the decision to proceed being agreed. · as a minimum standard, all women can undergo the abortion within 2 weeks of the decision to proceed being agreed. · as a minimum standard, no woman need wait longer than 3 weeks from her initial referral to the time of her abortion. · women should be seen as soon as possible if they require termination for urgent medical reasons.

2.

3.

B

4. 5. 6.

7.

C

7

The Care of Women Requesting Induced Abortion

8. 9. The assessment appointment should be within clinic time dedicated to women requesting abortion. In the absence of specific medical, social or geographical contraindications, induced abortion may be managed on a day case basis.

C

10. An adequate number of staffed inpatient beds must be available for those women who are unsuitable for daycase care. In a typical abortion service, up to 5% of women will require inpatient care. 11. As far as possible, women admitted for abortion should be cared for separately from other gynaecological patients. 12. Women having second-trimester abortions by medical means must be cared for by an appropriately experienced midwife or nurse. Ideally, they should have the privacy of a single room.

2.2 Information for women

B 13. Verbal advice should be supported by accurate, impartial printed information that the woman considering abortion can understand and may take away to consider further before the procedure. 14. The use of nationally developed patient information (such as that produced by the RCOG or fpa) ensures accuracy and readability. Services are encouraged to adapt national information to reflect local circumstances or to supplement a national leaflet with a sheet summarising local details. 15. Information for women and professionals should emphasise the duty of confidentiality by which, as for any form of health care, all concerned with the provision of induced abortion are bound. 16. Clinicians providing abortion services should possess accurate knowledge about possible complications and sequelae of abortion. This will permit them to provide women with the information they need in order to give valid consent. 16.1 The risk of haemorrhage at the time of abortion is low. It complicates around 1 in 1000 abortions overall. The risk is lower for early abortions (0.88 in 1000 at less than 13 weeks; 4.0 in 1000 at more than 20 weeks). 16.2 The risk of uterine perforation at the time of surgical abortion is moderate. The incidence is of the order of 1­4 in 1000. The risk is lower for abortions performed early in pregnancy and those performed by experienced clinicians. 16.3 Uterine rupture has been reported in association with mid-trimester medical abortion. However, the risk is very low, at well under 1 in 1000. 16.4 Cervical trauma: the risk of damage to the external cervical os at the time of surgical abortion is moderate (no greater than 1 in 100). The risk is lower when abortion is performed early in pregnancy and when it is performed by an experienced clinician.

B

B

B B

8

Summary of recommendations

16.5 Failed abortion and continuing pregnancy: all methods of first-trimester abortion carry a small risk of failure to terminate the pregnancy, thus necessitating a further procedure. The risk for surgical abortion is around 2.3 in 1000 and for medical abortion between 1 and 14 in 1000 (depending on the regimen used and the experience of the centre). 16.6 Post-abortion infection: genital tract infection, including pelvic inflammatory disease of varying degrees of severity, occurs in up to 10% of cases. The risk is reduced when prophylactic antibiotics are given or when lower genital tract infection has been excluded by bacteriological screening. 16.7 Breast cancer: induced abortion is not associated with an increase in breast cancer risk. 16.8 Future reproductive outcome: there are no proven associations between induced abortion and subsequent ectopic pregnancy, placenta praevia or infertility. Abortion may be associated with a small increase in the risk of subsequent miscarriage or preterm delivery. 16.9 Psychological sequelae: some studies suggest that rates of psychiatric illness or self-harm are higher among women who have had an abortion compared with women who give birth and to nonpregnant women of similar age. It must be borne in mind that these findings do not imply a causal association and may reflect continuation of pre-existing conditions.

B

B

B B

B

2.3 Pre-abortion management

The abortion decision

C 17. Clinicians caring for women requesting abortion should try to identify those who require more support in decision making than can be provided in the routine clinic setting (such as those with a psychiatric history, poor social support or evidence of coercion). Care pathways for additional support, including access to social services, should be available.

Blood tests

C 18. Pre-abortion assessment should include: · measurement of haemoglobin concentration · determination of ABO and rhesus blood groups with screening for red cell antibodies · testing for other conditions such as haemoglobinopathies, HIV, and hepatitis B and C if indicated in the light of clinical features, individual risk factors or local prevalence. 19. It is not cost effective routinely to crossmatch women undergoing induced abortion.

B

Cervical cytology

20. Assessment prior to induced abortion may be viewed as an opportunity to ascertain each woman's cervical cytology history. Women who have not had a cervical smear within the interval recommended in their local programme may be offered one within the abortion service.

9

The Care of Women Requesting Induced Abortion

21. If a cervical smear is taken within the abortion service, then mechanisms are essential to ensure that the smear result is communicated to the woman, acted on appropriately and recorded within the local cervical cytology programme.

Ultrasound scanning

B 22. All services must have access to scanning, as it can be a necessary part of pre-abortion assessment, particularly where gestation is in doubt or where extrauterine pregnancy is suspected. However, ultrasound scanning is not considered to be an essential prerequisite of abortion in all cases. 23. When ultrasound scanning is undertaken, it should be in a setting and manner sensitive to the woman's situation. It is inappropriate for pre-abortion scanning to be undertaken in an antenatal department alongside women with wanted pregnancies.

C

Prevention of infective complications

A B C 24. Abortion care should encompass a strategy for minimising the risk of post-abortion infective morbidity. As a minimum, services should offer antibiotic prophylaxis. Ideally, services should offer testing for lower genital tract organisms with treatment of positive cases. 25. The following regimens are suitable for periabortion prophylaxis: · metronidazole 1 g rectally at the time of abortion plus · doxycycline 100 mg orally twice daily for 7 days, commencing on the day of abortion OR · metronidazole 1 g rectally at the time of abortion plus · azithromycin 1 g orally on the day of abortion.

2.4 Abortion procedures

B 26. As a minimum, all services should be able to offer abortion by one of the recommended methods for each gestation band. 27. Ideally, abortion services should be able to offer a choice of recommended methods for each gestation band.

Surgical methods

B B 28. Conventional suction termination should be avoided at gestations below 7 weeks. 29. Early surgical abortion using a rigorous protocol (which includes magnification of aspirated material and indications for serum hCG follow-up) may be used at gestations below 7 weeks, although data suggest that the failure rate is higher than for medical abortion. 30. Conventional suction termination is an appropriate method at gestations of 7­15 weeks, although, in some settings, the skills and experience of practitioners may make medical abortion more appropriate at gestations above 12 weeks.

B

10

Summary of recommendations

31. During suction termination, the uterus should be emptied using the suction curette and blunt forceps (if required) only. The procedure should not be completed by sharp curettage. 32. Suction termination is safer under local anaesthesia than under general anaesthesia. Consideration should be given to making this option available, particularly for lowgestation procedures. 33. If conscious sedation is used in place of general anaesthesia to reduce the pain and anxiety associated with surgical abortion, it should be undertaken only by trained practitioners and in line with Department of Health guidance. 34. For first-trimester suction termination, either electric or manual aspiration devices may be used, as both are effective and acceptable to women and clinicians. Operating times are shorter with electric aspiration. 35. For gestations above 15 weeks, surgical abortion by dilatation and evacuation (D&E), preceded by cervical preparation, is safe and effective when undertaken by specialist practitioners with access to the necessary instruments and who have a sufficiently large caseload to maintain their skills. 36. Cervical preparation is beneficial prior to surgical abortion and should be routine if the woman is aged under 18 years of age or at a gestation of more than 10 weeks. 37. Abortion regimens containing misoprostol are not licensed within manufacturers' summaries of product characteristics. European Community regulations permit doctors to prescribe unlicensed regimens and permit pharmacists to dispense and nurses to administer medicines prescribed outside of a product licence. Women should be informed if a prescribed treatment is unlicensed. 38. Based on available evidence, the following regimen appears to be optimal for cervical preparation prior to first- or second-trimester surgical abortion. This advice is based on considerations of efficacy, adverse-effect profile and cost: * misoprostol 400 micrograms (2 x 200-microgram tablets) administered vaginally, either by the woman or a clinician, 3 hours prior to surgery. The following regimens are licensed within manufacturers' summaries of product characteristics and are also appropriate for cervical preparation prior to first- or secondtrimester surgical abortion: · gemeprost 1 mg vaginally, 3 hours prior to surgery · mifepristone 600 mg orally 36­48 hours prior to surgery.

B

C

A

A

B C

B

Medical methods

B A 39. Medical abortion using mifepristone plus prostaglandin is the most effective method of abortion at gestations of less than 7 weeks. 40. Medical abortion using mifepristone plus prostaglandin continues to be an appropriate method for women in the 7­9 week gestation band.

* This regimen is unlicensed.

11

The Care of Women Requesting Induced Abortion

41.* For early medical abortion a dose of 200 mg of mifepristone in combination with a prostaglandin is appropriate. 42.* Misoprostol (a prostaglandin E1 analogue) is a cost-effective alternative for all abortion procedures for which the E1 analogue gemeprost is conventionally used (that is, early medical abortion, cervical priming, mid-trimester medical abortion). 43. Based on available evidence, the following regimen appears to be optimal for early medical abortion up to 9 weeks (63 days) of gestation. This advice is based on considerations of efficacy, adverse-effect profile and cost: * mifepristone 200 mg orally followed 1­3 days later by misoprostol 800 micrograms vaginally. The misoprostol may be administered by a clinician or self-administered by the woman. For women at 49­63 days of gestation, if abortion has not occurred 4 hours after administration of misoprostol, a second dose of misoprostol 400 micrograms may be administered vaginally or orally (depending upon preference and amount of bleeding). The following regimen is licensed within manufacturer's summary of product characteristics and is also appropriate for early medical abortion up to 9 weeks (63 days) of gestation: * mifepristone 600 mg orally followed 36­48 hours later by gemeprost 1 mg vaginally. A 44. Medical abortion using the following regimen is a safe, effective and acceptable alternative to surgical abortion for women between 9 and 13 weeks of gestation: * mifepristone 200 mg orally followed 36­48 hours later by misoprostol 800 micrograms vaginally. A maximum of four further doses of misoprostol 400 micrograms may be administered at 3-hourly intervals, vaginally or orally (depending on the amount of bleeding). B 45. For mid-trimester abortion (13­24 weeks of gestation) medical abortion with mifepristone followed by prostaglandin is an appropriate method and has been shown to be safe and effective. 46. For mid-trimester medical abortion, a dose of *200 mg of mifepristone is adequate. 47. Surgical evacuation of the uterus is not required routinely following mid-trimester medical abortion. It should only be undertaken if there is clinical evidence that the abortion is incomplete. 48. Based on available evidence, the following regimen appears to be optimal for midtrimester medical abortion. This advice is based on considerations of efficacy, adverseeffect profile and cost: * mifepristone 200 mg orally, followed 36­48 hours later by misoprostol 800 micrograms vaginally, then misoprostol 400 micrograms orally, 3-hourly, to a maximum of four oral doses. The following regimen is licensed within manufacturer's summary of product characteristics and is also appropriate for mid-trimester medical abortion. * mifepristone 600 mg orally, followed 36­48 hours later by gemeprost 1 mg vaginally every 3 hours, to a maximum of five pessaries. * This regimen is unlicensed.

A A

B

A B

A

12

Summary of recommendations General

B 49. Some women will require analgesia after surgical abortion or during and after medical abortion. Requirements for analgesia vary and there is no benefit in routine administration of prophylactic analgesics. Services should make available a range of oral and parenteral analgesics in order to meet women's needs. 50. Routine histopathological examination of tissue obtained at abortion procedures is unnecessary.

B

2.5 Aftercare

Rhesus prophylaxis

B 51. Anti-D immunoglobulin G (250 iu before 20 weeks of gestation and 500 iu thereafter) should be given, by injection into the deltoid muscle, to all nonsensitised RhD negative women within 72 hours following abortion, whether by surgical or medical methods.

Post-abortion information and followup

52. Following abortion, women must be given a written account of the symptoms they may experience and a list of those that would make an urgent medical consultation necessary. They should be given a 24-hour telephone helpline number to use if they feel worried about pain, bleeding or high temperature. Urgent clinical assessment and emergency gynaecology admission must be available when necessary. 53. Each woman should be offered, or advised to obtain, a follow-up appointment (either within the abortion service or with the referring clinician) within 2 weeks of the abortion. 54. On discharge, each woman should be given a letter that includes sufficient information about the procedure to allow another practitioner elsewhere to deal with any complications. 55. Referral for further counselling should be available for the small minority of women who experience long-term post-abortion distress. Risk factors are ambivalence before the abortion, lack of a supportive partner, a psychiatric history or membership of a cultural group that considers abortion to be wrong.

C

C

Contraception following abortion

B 56. Before she is discharged following abortion, future contraception should have been discussed with each woman and contraceptive supplies should have been offered if required. The chosen method of contraception should be initiated immediately following abortion. 57. Intrauterine contraception can be inserted immediately following a first- or secondtrimester termination of pregnancy. 58. Sterilisation can be safely performed at the time of induced abortion. However, combined procedures are associated with higher rates of failure and of regret on the part of the woman.

B B

13

Chapter 3

Legal and ethical aspects of abortion

3.1 The Abortion Act

Current abortion legislation in Great Britain is based on the Abortion Act 1967,14 the modifications introduced by the Human Fertilisation and Embryology Act 199015 and, for England and Wales, on further amendments made in 2002 (summarised in Statutory Instrument 2002 No. 887).16 Legal requirements apply to certification and notification of abortion procedures. A certificate signed by the two medical practitioners authorising the abortion must be retained for a period of at least 3 years and the operating practitioner must complete a notification form and forward it to the Chief Medical Officer for the relevant UK country. Within the terms of the Abortion Act, only a registered medical practitioner can terminate a pregnancy: the notification form must be signed by the doctor taking responsibility for the procedure. In practice, a nurse or midwife may administer the drugs used for medical abortion once these have been prescribed by the doctor concerned. For England, the 2002 amendments to the Abortion Act16 changed the content of the HSA4 form through which medical practitioners notify the Chief Medical Officer of every abortion performed. Guidance notes on completing the amended form have been published.17 Wales has also adopted the amended HSA4. Key features of the 2002 amendment are: · to increase the timescale for notification from 7 to 14 days · to include the General Medical Council (GMC) registration number of the practitioner terminating the pregnancy · to allow the option of identifying the woman only by her hospital or clinic or NHS reference number, rather than by her full name · to include data on ethnicity · to specify if feticide was undertaken as part of the abortion procedure · to specify if Chlamydia screening was offered. The Abortion Act does not apply in Northern Ireland. Some abortions are performed there and categorised as therapeutic. Abortion is available if the woman has a serious medical or psychological problem that would jeopardise her life or health if the pregnancy continued, if she has severe learning difficulties or if a fetal abnormality is detected. It is unclear at what gestations such abortions may be performed and no official abortion statistics are collected.18 A judicial review of medical practices relating to abortion services in Northern Ireland, initiated by the fpa, is currently under appeal. This review may result in clarification of the status of abortion in Northern Ireland.

14

Legal and ethical aspects of abortion Statutory grounds for termination of pregnancy

Abortion is legal in Great Britain if two doctors decide in good faith that a particular pregnancy is associated with factors that satisfy one or more of five grounds specified in the Regulations of the Abortion Act14,16 and Section 37 of the Human Fertilisation and Embryology Act 1990:15 A B C The continuance of the pregnancy would involve risk to the life of the pregnant woman greater than if the pregnancy were terminated. The termination is necessary to prevent grave permanent injury to the physical or mental health of the pregnant woman. The pregnancy has not exceeded its 24th week and the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman. The pregnancy has not exceeded its 24th week and the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the existing child(ren) of the family of the pregnant woman. There is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped.

D

E

The Regulations also permit abortion to be performed in an emergency on the basis of the signature of the doctor performing the procedure, which may be provided up to 24 hours after the termination. The emergency grounds are: F G To save the life of the pregnant woman. To prevent grave permanent injury to the physical or mental health of the pregnant woman.

Most abortions are undertaken on grounds C or D: that the pregnancy has not exceeded its 24th week and that continuance would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the woman or of the existing children of her family. As an illustration, in England and Wales in 2002, the vast majority (94%) of abortions were undertaken under ground C and 4% under ground D. Grounds A and B together accounted for just over 1% of abortions and a similar proportion were under ground E. The proportion of ground C abortions has risen steadily since 1992, with a corresponding reduction in grounds B and D cases. Abortions are rarely performed under grounds F or G: in 2002 there was one case reported.1 Similarly, in Scotland in 2002, 98.5% of abortions were undertaken on grounds C or D, 0.2% on grounds A or B and 1.2% on ground E. No abortions on the emergency grounds (F or G) have been notified in Scotland during the last three years.2 The WHO definition of health is "a state of physical and mental wellbeing, not merely an absence of disease or infirmity".19 Most doctors apply this broad definition of health in interpreting the Abortion Act. Thus, to meet the terms of the Act, a woman need not have a psychiatric illness when she makes her abortion request but there must be factors that would involve risk to her mental health if the pregnancy were to continue. Thus, the abortion is not carried out for social reasons, although a woman's social circumstances may be taken into account in assessing the risks to her health. The requirements of the Abortion and Human Fertilisation and Embryology Acts are discussed further within Chapter 4, Organisation of services.

15

The Care of Women Requesting Induced Abortion

3.2 Good professional practice

Doctors providing abortion care are bound by the same duties of a doctor, as laid down by the GMC,20 as for all other aspects of their clinical practice. These principles of good practice bear repetition here: · · · · · · · · · · · · make the care of your patient your first concern treat every patient politely and considerately respect patients' dignity and privacy listen to patients and respect their views give patients information in a way they can understand respect the right of patients to be fully involved in decisions about their care keep your professional knowledge and skills up to date recognise the limits of your professional competence be honest and trustworthy respect and protect confidential information make sure that your personal beliefs do not prejudice your patients' care act quickly to protect patients from risk if you have good reason to believe that you or a colleague may not be fit to practice · avoid abusing your position as a doctor · work with colleagues in the ways that best serve patients' interests.

The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) (now the Nursing and Midwifery Council) published a Code of Professional Conduct21 and Guidelines for Professional Practice22 equivalent to the GMC's Duties of a Doctor. The guidance provided in these documents is similar in spirit and in actual wording to the Duties of a Doctor summarised above (the content of these two documents has now been combined in the Nursing and Midwifery Council's Code of Professional Conduct).23

3.3 Confidentiality

All women seeking abortion have the right to confidentiality from all clinical and ancillary staff. Only in exceptional circumstances, where the health, safety or welfare of a minor, or other persons, is at risk should information be disclosed to a third party. Similarly, if a minor is a ward of court or in care disclosure may be considered appropriate.24 Data on all women undergoing abortion must be collected on the HSA4 form or other relevant form, for the Chief Medical Officer. These data are not anonymised and, although names and addresses are not generally recorded, date of birth, postcode and reference number may allow the woman to be identified. Forms are held securely and only individuals authorised by the Chief Medical Officer have access. Information can be disclosed in rare instances, within the terms of the Abortion Regulations. Women should be informed that abortion procedures are notified centrally, but can be reassured as to the confidentiality and security of the data.

3.4 Professionals' rights: conscientious objection to abortion

The Abortion Act14 has a conscientious objection clause which permits doctors to refuse to participate in terminations. The scope of the Act's conscientious objection clause was clarified in a Department of Health Parliamentary answer25 and in a circular, Health Service Guidance

16

Legal and ethical aspects of abortion

HSG(94)39.26 The British Medical Association (BMA) has produced a helpful overview on the law and ethics of abortion, based on a comprehensive review of relevant legal documents.27 The following represents a summary of the BMA's conclusions relating to interpretation of the conscientious objection clause: · Doctors may refuse to participate in terminations but are obliged to provide necessary treatment in an emergency, when the woman's life may be jeopardised. · Doctors with a conscientious objection may not impose their views on others, but may explain their views to a patient if invited to do so. · The Parliamentary answer25 clarifies that the conscientious objection clause was only intended to be applied to participation in treatment. Subsequently, however, hospital managers have been asked to apply the principle, at their discretion, to those ancillary staff involved in handling fetuses and fetal tissue. · Refusal to participate in paperwork or administration connected with abortion procedures lies outside the terms of the conscientious objection clause. · Practitioners cannot claim exemption from giving advice or performing the preparatory steps to arrange an abortion where the request meets the legal requirements. Such steps include referral to another doctor, as appropriate. · The conscientious objection clause may be used by medical students to opt out of witnessing abortions. In law, nurses have similar rights to conscientious objection. These are summarised in the NMC Code of Professional Conduct.23 Like doctors, nurses have the right to refuse to take part in abortion but not to refuse to take part in emergency treatment.

3.5 Issues relating to consent to treatment

The 2000 guideline contained advice on patient consent based on the following sources: the Medical Defence Union's Consent to Treatment,28 the BMA's Law and Ethics of Abortion,27 and the GMC's guidance Seeking Patients' Consent.29 In 2001, the Department of Health published comprehensive guidance in its Reference Guide to Consent for Examination or Treatment.30 The advice which follows has been updated with reference to the latter document.

Competent adults

In the case of an adult woman (that is, aged over 18 years), for consent to be valid it must be given voluntarily, on the basis of appropriate information, and the woman must have the capacity to consent to the intervention in question. The GMC has summarised criteria for valid consent:29 · the woman must have sufficient capacity to understand the procedure and its alternatives · the consent must be voluntary · the decision must be based on sufficient and accurate information. A good working test for assessing capacity to consent to or refuse medical treatment was outlined by Mr. Justice Thorpe31 and has been reiterated in the BMA document.27 This test is based on the patient having the ability: · to take in and retain treatment information · to believe the information · to weigh the information, balancing risks and needs.

17

The Care of Women Requesting Induced Abortion Non-competent adults

Under English law, no one can consent to treatment on behalf of another adult (that is, someone over the age of 18 years) who is unable to give consent for herself (an `incapable' adult). Parents, relatives or healthcare professionals, therefore, cannot consent on behalf of such an adult. An authoritative text32 provides reassurance that provided the terms of the Abortion Act are complied with, a High Court declaration is not required. Rather, the professional's assessment of the woman's best interests should be the basis of the decision where the woman lacks the capacity to give valid consent. The Medical Defence Union's Consent to Treatment28 provides similar reassurance that while certain procedures (such as sterilisation or donation of organs or bone marrow) would require application to court before being undertaken on a non-competent adult, this does not apply to abortion. The document does advise, however, that if a practitioner is in any doubt about what constitutes the best interests of a non-competent adult patient, then a second opinion should be sought from `another appropriate doctor'. In Scotland, the Adults with Incapacity (Scotland) Act 200033 provides a framework for medical treatment of incapacitated adults (that is, those aged 16 years or more). The Act works alongside common law, which allows treatment in an emergency to people who are unable to give consent. If an adult lacks the capacity to make healthcare decisions and no proxy decision maker is appointed, a certificate of incapacity must be issued in order to provide care or treatment. Once a certificate has been issued, doctors can act under the general authority to treat. There are provisions within the Incapacity (Scotland) Act on the treatment of patients with mental disorder. Under the Incapacity (Scotland) Act, in addition to meeting the requirements of the Abortion Act, approval of a practitioner appointed by the Mental Welfare Commission is required before abortion can be performed. Guidance on interpretation and application of the Adults with Incapacity (Scotland) Act has been provided by the BMA.32

Competent minors

Young people aged 16­17 years By virtue of Section 8 of the Family Law Reform Act 1969, people aged 16 or 17 years are entitled to consent to their own medical treatment. However, unlike adults, the refusal of a competent person aged 16 or 17 years may, in certain circumstances, be overridden by a person with parental responsibility or by a court. In order to establish whether a young person aged 16 or 17 years has the requisite capacity to consent to an intervention, the same criteria as for adults should be used. If the requirements for valid consent are met, it is not legally necessary to obtain consent from a person with parental responsibility. However, it is good practice to involve the young person's family in decision making, unless the young person specifically wishes to exclude them. Young people aged under 16 years The House of Lords ruling in the Gillick case was followed by the issuing of guidance by the Department of Health in the form of a Health Circular [HC(FP)(86)1].35 The legal position was stated as "any competent young person, regardless of age, can give valid consent to medical treatment". The same working test for assessing capacity to consent to treatment outlined by Mr. Justice Thorpe31 and described above in relation to the competent adult can be applied in the case of a young person. Following the Gillick case, Lord Fraser provided the Fraser criteria28 to guide doctors asked

18

Legal and ethical aspects of abortion

to provide contraception for girls aged under 16 years who refuse to involve their parents. These criteria are worded to apply only to provision of contraception, but provide guidance similar to that provided by Mr Justice Thorpe. A doctor is justified in proceeding without the parent's consent or knowledge if: · the girl will understand his advice · he cannot persuade her to inform her parents or to allow him to inform the parents that she is seeking contraceptive advice · she is likely to begin or to continue having sexual intercourse with, or without, contraceptive advice · unless she receives contraceptive advice or treatment her physical or mental health, or both, are likely to suffer · her best interests require him to give her contraceptive advice, treatment, or both, without parental consent. Doctors have an obligation to encourage a young person to involve her parents but generally should not override the patient's views. Only in the most exceptional cases, perhaps where the pregnancy is thought to have resulted from child abuse, incest or exploitation, may a breach of confidentiality be justifiable. In such cases, the patient must be informed that confidentiality cannot be guaranteed and offered all necessary help and support. Legislation in Scotland relating to consent for medical, surgical and dental procedures is based on the Age of Legal Capacity (Scotland) Act 1991. Under the terms of this Act, the situation regarding age of consent (16 years) and the rights of a competent minor to give their own consent are the same as for the rest of the UK. Wards of court The main exception to this general guidance is if the young woman is a ward of court. In such cases, the courts would need to approve a termination. It is therefore particularly important that medical records make it clear if a child is a ward of court. Similarly, if a young woman seeking abortion is in the care of a local authority she should be encouraged to involve the local social services. If, in such a case, the young woman refuses consent to such sharing of information, then individual legal advice should be sought. Again, the advice of the BMA27 and MDU28 is similar on this issue.

Non-competent minors

Only a holder of `parental responsibility', or the court, can give consent to treatment on behalf of a minor. Adults who do not hold parental responsibility cannot give such consent. In rare cases, where a young person seeking abortion is not felt to be competent to provide valid consent and where a parent (or other holding parental responsibility) cannot give consent on the child's behalf, then it may be wise to obtain a court order. Similar advice is provided in both the BMA27 and MDU28 publications.

3.6 Abuse of children and vulnerable people

There are special difficulties in managing suspected child abuse, incest or abuse of the very vulnerable in abortion services. The need for a decision on a termination may be urgent because of

19

The Care of Women Requesting Induced Abortion

advanced gestation and both the girl and any accompanying adult usually conceal the truth from assessing staff. The girl may have travelled away from her home area to assist with the concealment. Staff must be alert to the possibility of abuse, particularly when the girl refuses to involve her parents or general practitioner, or is accompanied by a controlling adult such as a male relative who wishes to remain particularly close to her. When abuse is suspected, the primary concern must be the wellbeing of the girl and any siblings. Clear protocols must be in place for all assessors, medical staff, nurses and counsellors on action to be taken should abuse be suspected. It is suggested that all services should designate a small number of doctors and counsellors to assess all girls under 16 years. Within the terms of confidentiality, it would be their responsibility to liaise with the appropriate social services child protection group when there is strong evidence that a girl has been abused or when other children are likely to be at risk. Further guidance has been issued as an addendum to Working Together ­ Under the Children Act 1989.36 Similar considerations can arise in the case of vulnerable women (perhaps because of mental handicap). The duty of a doctor who learns of such an allegation or has other reason to suspect abuse is to protect the child and secure the best possible outcome for that child. The accepted professional, ethical view is that where a doctor believes that a patient (whether or not that patient is a child) may be the victim of abuse or neglect, the patient's interests are paramount, and will usually require a doctor to disclose information to an appropriate responsible person or officer of a statutory agency. In the case of children, the responsibilities of doctors are set out in the document, Child Protection: Medical Responsibilities. Guidance for Doctors Working with Child Protection Agencies.36 Disclosure is not invariably required but it is usual in order that the interests of the child, which are paramount, may be protected. A doctor may be called upon to justify before the court or the statutory professional body, the GMC, the action that he or she has taken. When such concerns arise in the context of abortion, whether during counselling or subsequently, the duty of the doctor is clear, and those who practise in this field should ensure that they are familiar with the procedures to be observed. A doctor should also bear in mind that other children in a family may be in need of protection. The report of the Climbie Enquiry37 includes healthcare recommendations which clarify the actions which individual clinicians and NHS trusts should take in cases where deliberate harm of a child is identified.

3.7 Rights of the spouse or partner

The decision to terminate a pregnancy rests with the woman and her doctors. Legally, the woman's spouse and/or the putative father of the child has no rights to demand or refuse a termination.38 In individual cases which attracted much media attention (Kelly, 1997; Hansell, 2001) male partners brought unsuccessful legal actions in attempts to prevent women obtaining abortions.

3.8 Disposal of fetal tissue

For fetuses born dead at or before 24 weeks of gestation, Department of Health guidance HSG(91)19 on the disposal of fetal tissue applies.39 It states that "all fetuses and fetal tissue from termination of pregnancy must be incinerated" but also that "full account should be taken of any personal wishes that have been expressed about disposal which require some other method to be used". The Royal College of Nursing (RCN) published guidance for nurses and midwives on Sensitive Disposal of All Fetal Remains in 1991.41

20

Legal and ethical aspects of abortion

Other methods of disposal chosen by the woman or couple may include a privately arranged cremation or burial. The opportunity to do this will vary, depending on the policies of the local crematoria and burial authorities, who can exercise discretion. Alternatively, the woman or couple may decide to bury the fetus themselves. The Department of Health has advised that there is no legal prohibition on where the fetus is buried, provided that no danger is caused to others and there is no interference with any rights that other people may have over the land used. In general, abortion service providers arrange for fetal material to be incinerated but some have chosen to have a contract with the local crematoria or burial authorities for cremation or burial. However, if a woman requests that she be allowed to make alternative private arrangements as set out above, there is no legal obstacle to this. Among women who have an early medical abortion (up to 63 days), a small minority choose to pass the products of conception outside of hospital or clinic premises. The Department of Health advises that abortion service providers should make provision for a woman to return products of conception to the provider for disposal if she so wishes. A woman or couple should be made aware that information on disposal options is available if they wish to have access to it. If they then decide not to receive any information about, or take part in, the disposal of the fetal tissue, their wishes should be respected. Further information on the disposal of fetal tissue from pregnancies lost before 24 weeks will soon be available from the Department of Health. Terminations carried out after 24 weeks of gestation are required by law to be registered as stillbirths and for the body to be buried or cremated. However, these circumstances lie outwith the scope of this guideline, which focuses on abortions undertaken on Grounds `C' and `D', restricted to pregnancies under 24 weeks.

21

Chapter 4

Organisation of services

In the view of the Guideline Development Group and the Update Group, the aim of an abortion service is to provide high-quality, efficient, effective and comprehensive care, which respects the dignity, individuality and rights of women to exercise personal choice over their treatment. Ideally, an abortion service should be an integral component of a broader service for reproductive and sexual health, encompassing contraception and management of sexually transmitted infections.

4.1 Access and referral to abortion services

RECOMMENDATION 1

Abortion services should have local strategies in place for providing information to both women and healthcare professionals on the choices available within the service and on routes of access to the service.

RECOMMENDATION 2

Access to services should be ensured for women with special needs. For example, as appropriate, special arrangements should be made for non-English-speaking women and a woman doctor should be available.

RECOMMENDATION 3

It is helpful if the referring doctor is able to provide the first signature on Certificate A. If a woman refers herself, or if the referring doctor is not willing to support the abortion, it must be possible for the woman to be assessed by a second doctor within the abortion service.

RECOMMENDATION 4

Any woman considering induced abortion should have access to clinical assessment.

RECOMMENDATION 5

Appropriate information and support should be available for those who consider but do not proceed to abortion.

22

Organisation of services Evidence supporting recommendations 1 to 5

Recommendations based on group consensus.

RECOMMENDATION 6

B The earlier in pregnancy an abortion is performed, the lower the risk of complications. Services should therefore offer arrangements that minimise delay (for example, a telephone referral system and a formal care pathway with arrangements for access from a wide range of referral sources, not just general practitioners).

Evidence supporting recommendation 6

The absolute risk of complications at the time of abortion is low. For example, a retrospective cohort study of 83 469 procedures42 reported 571 immediate complications (0.7%). The complications included haemorrhage (greater than 500 ml), cervical laceration, uterine perforation, retained products, infection and maternal death. Against this background of low absolute risk, level IIb evidence (from large cohort studies)42­45 suggests that increasing gestational age is associated with an increasing relative risk of complications of abortion. For example, the study of Ferris et al. from Ontario42 found odds ratios for immediate complications of 1.3 (95% CI 1.02­1.63) at 9­12 weeks of gestation and of 3.3 (95% CI 2.23­5.00) at 17­20 weeks, compared with procedures at or below 9 weeks. Similarly, a US cohort study of over 82 000 women showed that the relative risk of serious complications increased by 1.42 (95% CI 1.30­1.55) for every 2-week increment in gestation beyond 12 weeks.45 Below this gestation, there was no significant overall increase in serious complications but there was an increase specifically for haemorrhage requiring transfusion: the relative risk for each 2-week gestation increment was 2.0 (95% CI 1.10­3.64) below 12 weeks and 1.48 (95% CI 1.33­1.65) beyond this age. A MEDLINE search covering the years 1976­2003 revealed only one study suggesting that later abortion is as safe as that undertaken earlier (15­20 weeks versus less than 15 weeks). This was a relatively small cohort study of 3772 women.46 Level III evidence, in the form of a before-and-after study, is available to show that organisational change (in the form of a telephone referral service with the provision of dedicated outpatient appointment time) is reflected in earlier abortion.47 The supporting evidence cited in this section is summarised in Evidence table 1 in the Appendix.

4.2 Waiting times in abortion services

RECOMMENDATION 7

Service arrangements should be such that: · ideally, all women requesting abortion are offered an assessment appointment within 5 days of referral. · as a minimum standard, all women requesting abortion are offered an assessment appointment within 2 weeks of referral.

23

The Care of Women Requesting Induced Abortion

· ideally, all women can undergo the abortion within 7 days of the decision to proceed being agreed. · as a minimum standard, all women can undergo the abortion within 2 weeks of the decision to proceed being agreed. · as a minimum standard, no woman need wait longer than 3 weeks from her initial referral C to the time of her abortion. · women should be seen as soon as possible if they require termination for urgent medical reasons.

Evidence supporting recommendation 7

The Birth Control Trust48 suggested 5 and 7 days as appropriate targets for referral to assessment and assessment to procedure intervals, respectively. These same targets were endorsed by a consensus survey of Scottish gynaecologists.49 The Guideline Development Group supported these target intervals as an ideal towards which services might aspire. The National Strategy for Sexual Health,8 published in 2001, reiterated the RCOG minimum standard that women should "have access to an abortion within 3 weeks of the first appointment with a GP or other referring doctor". The Guideline Update Group emphasised that these targets refer to the offer of an appointment for assessment or an abortion procedure. Some women will choose not to take up the first appointment either because they wish to have more time to reach a decision or for a range of individual reasons. The Update Group also emphasised the importance of services working towards waiting times shorter than these targets. A report from the fpa advocates a target of 72 hours for the assessment to procedure interval, with 1 week as the minimum standard.50

4.3 Settings for abortion care

Approval of independent sector places to undertake termination of pregnancy

The Abortion Act (Subsection 3) requires that termination of pregnancy is carried out in an NHS hospital or in a place approved by the Secretary of State. Before giving approval to a non-NHS place, the Secretary of State must be satisfied that the proprietor will comply with certain conditions. Since 1 October 1999, the document, Procedures for the Approval of Independent Sector Places for the Termination of Pregnancy,51,52 has governed approval of non-NHS places in England wishing to undertake abortion procedures. The aims of the procedures51,52 are to ensure that there is compliance with the legal requirements, that places provide the best quality of care for women, and that they have sound management and organisational arrangements. The documents highlight the importance of authoritative professional standards of care, supported by guidelines to assist in achieving them, complemented by arrangements for audit of the service and of clinical practice. It is expected that this guideline on induced abortion will be adopted by independent sector providers, alongside the NHS, in support of these aims. Until April 2002, the Department of Health undertook regular inspections of independent sector abortion establishments to ensure adherence with the procedures. In April 2002, the National Care Standards Commission (as of 1 April 2004, the Healthcare Commission) became fully operational and, for England, now includes these Department of Health inspection responsibilities within its remit. The Commission is a national, independent body established under the Care Standards Act

24

Organisation of services

2000. It is responsible for regulating a wide range of services including care homes, children's homes, private hospitals and clinics. National minimum standards have been published which apply to all settings for independent health care.53 This document contains a specific section on termination of pregnancy establishments, which includes five individual standards. In brief, these standards cover: · adherence to the Healthcare Commission core and acute services standards53 and to the procedures for the approval of independent sector places for the termination of pregnancy51,52 · provision of appropriate information for patients both before and after the procedure · confidentiality of consultations and records · sensitive disposal of fetal tissue · emergency transfer arrangements for complications of abortion.

Medical abortion in settings other than NHS hospitals or places approved by the Secretary of State

The 1990 amendment to the Abortion Act introduced a subsection 1(3a)16 which indicated that the Secretary of State has power "in relation to treatment consisting primarily in the use of such medicines as may be specified in the approval and carried out in such manner as may be so specified, to approve a class of places". This subsection acknowledges that medical abortion might appropriately be carried out in places different from those approved for surgical abortion. Thus, a mechanism exists within the law for places to be approved specifically for medical abortion. To date, no places in England have been approved under Subsection 1(3a). However, two early medical abortion pilots, which will be run from non-traditional settings that meet the legal requirements, will enable the Department of Health to define a `class of place'. Since publication of the first edition of this guideline in 2000, reports have appeared in the international literature on the effectiveness54­59 and acceptability60­62 of `home medical abortion'. These publications describe regimens for early medical abortion where, following hospital or clinic administration of mifepristone, the abortion is completed by use of the prostaglandin, misoprostol, self-administered at home. Studies in a number of settings, including the USA, Vietnam, Tunisia and Guadeloupe, indicate that a `home' regimen is both effective and acceptable. To date, there are no published reports of experience in UK settings and no recommendation on home medical abortion can be made for UK practice. Currently, Department of Health advice is that, for medical abortion to be undertaken within the law, both components of the treatment regimen (mifepristone and a prostaglandin) must be administered in an NHS hospital or in an approved private-sector place. In some settings, a family planning or sexual health clinic has been regarded as comprising part of an NHS hospital and mifepristone has been administered there.

RECOMMENDATION 8

The assessment appointment should be within clinic time dedicated to women requesting abortion.

Evidence supporting recommendation 8

Recommendation based on group consensus.

25

The Care of Women Requesting Induced Abortion RECOMMENDATION 9

In the absence of specific medical, social or geographical contraindications, induced abortion may be managed on a day case basis.

RECOMMENDATION 10

C An adequate number of staffed inpatient beds must be available for those women who are unsuitable for daycase care. In a typical abortion service, up to 5% of women will require inpatient care.

Evidence supporting recommendations 9 and 10

Daycase care is recognised as a cost effective model of service provision. The availability of abortion as a daycase procedure can minimise disruption to the lives of women and their families. Before 1999, under the Abortion Act the set of requirements known as the Assurances restricted daycase abortion in non-NHS settings to procedures performed before 14 weeks of gestation. Within the NHS, however, the introduction of treatment with mifepristone prior to mid-trimester abortion with prostaglandin reduced induction to abortion intervals to an extent such that many women undergoing these procedures may also be managed as day cases. In a series of 500 women undergoing mid-trimester prostaglandin abortion, over two-thirds were managed as day cases.63 Reasons why women might need to undergo induced abortion as inpatients rather than day cases include: · · · · · medical problems requiring assessment prior to anaesthetic social indications, such as lack of an adult companion at home geographical factors, such as distance or transport problems patient choice planned day case requiring overnight stay because of surgical or medical problems.

The Guideline Development Group suggested that up to 10% of women managed in a typical abortion service would require inpatient care for medical, social or geographical reasons (or a combination of these). As an illustrative guide, unpublished daycase figures for women managed during 1998 in the population-based abortion service in Aberdeen were presented. The overall daycase rate was 90%. The Aberdeen service serves a geographically scattered population, including women resident in Orkney and Shetland. It would be expected, therefore, that services in other settings might have a lower requirement for inpatient care on geographical grounds. The abortion charity bpas has provided figures for the percentage of women undergoing abortion within their service requiring an overnight stay. Of 45 241 women, 4.9% required an overnight stay. All 42 243 women who underwent abortion at gestations of less than 16 weeks were managed as day cases. On the basis of these data, the Update Group felt that 5% was a more realistic figure for overnight stay requirement in a typical service. The availability of beds for those women who require an overnight stay must be agreed locally to reflect local circumstances.

RECOMMENDATION 11

As far as possible, women admitted for abortion should be cared for separately from other gynaecological patients.

26

Organisation of services RECOMMENDATION 12

Women having second-trimester abortions by medical means must be cared for by an appropriately experienced midwife or nurse. Ideally, they should have the privacy of a single room.

Evidence supporting recommendations 11 and 12

These recommendations are based on the consensus view of the Guideline Development Group.

27

Chapter 5

Information for women

RECOMMENDATION 13

B Verbal advice should be supported by accurate, impartial printed information that the woman considering abortion can understand and may take away to consider further before the procedure.

RECOMMENDATION 14

The use of nationally developed patient information (such as that produced by the RCOG or fpa) ensures accuracy and readability. Services are encouraged to adapt national information to reflect local circumstances, or to supplement a national leaflet with a sheet summarising local details.

Evidence supporting recommendations 13 and 14

It is important that all information shared in the initial consultation is backed up by good-quality, accurate, impartial, written information that is well presented and easy to understand. It has generally been found that patients want to receive written information about medical and surgical interventions and that patients given written information are more likely to express satisfaction with the patient­health professional relationship.64­66 A 2002 study examined the quality of information relating to medical abortion available to the public on the Internet.67 Incorrect and inappropriate information was common. The ease with which women can access such information reinforces the importance of provision by abortion care professionals of accurate, locally relevant information. The RCOG report, Communication Standards in Gynaecology: Surgical Procedures,68 endorses the use of information leaflets and recommends that: "it should become part of the culture that people are given the appropriate leaflets". A randomised controlled trial has shown that providing leaflets improves knowledge of contraception in relation to oral contraceptive pill use.69 In one study, a formal content analysis was undertaken on 44 patient leaflets used by NHS and private providers of abortion services in England and Wales.70 Adequacy of information was low in relation to medical abortion, surgical abortion and aftercare. Readability scores were also poor. The RCOG produced information for women (About Abortion Care)71 based on the 2000 edition of this guideline and the fpa also developed a leaflet72 in a format to match its other patient information. The RCOG's updated information is published in 2004. Clinicians are advised to access the most recent patient information from the RCOG website (www.rcog.org.uk) and to base local leaflets on this information. A local supplement could be used alongside RCOG or fpa information.

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Information for women

In addition to providing written information, the needs of women who cannot read must be taken into account. The same information may need to be available on an audiotape for those who are blind or visually impaired, or who have limited literacy skills. Consideration should also be given to providing the information in a range of languages to suit local racial representation.

RECOMMENDATION 15

Information for women and professionals should emphasise the duty of confidentiality by which, as for any form of health care, all concerned with the provision of induced abortion are bound.

Evidence supporting recommendation 15

This recommendation was based on the consensus view of the 2000 Guideline Development Group. In November 2003, the Department of Health published an NHS Code of Practice on Confidentiality.73 This document provides clarity and transparency regarding the responsibilities of NHS staff regarding patient confidentiality.

RECOMMENDATION 16

Clinicians providing abortion services should possess accurate knowledge about possible complications and sequelae of abortion. This will permit them to provide women with the information they need in order to give valid consent.

Evidence supporting recommendation 16

In the view of the Guideline Development Group and of the Update Group, clinicians involved in abortion care should be equipped to provide women with accurate information relating to the following topics: · that abortion is safer than continuing a pregnancy to term and that complications are uncommon. · description of the method(s) of abortion available within the local service for particular gestations. · immediate complications including: haemorrhage, uterine perforation, cervical lacerations and anaesthetic complications. Women must be informed that, should one of these complications occur, further treatment in the form of blood transfusion, laparoscopy or laparotomy may be required. · complications in the early weeks following abortion, including: incomplete abortion requiring re-evacuation, continuing pregnancy requiring a further abortion procedure, pelvic infection, and short-term emotional distress. · long-term effects which may, rarely, be associated with abortion, including: miscarriage or preterm birth and psychological problems. · conditions where an association with abortion has been postulated but where evidence provides reassurance (such as breast cancer and infertility). The following represents a summary of currently available evidence relating to significant sequelae of, and postulated associations with, induced abortion. In summarising the degree of risk of the various complications and sequelae associated with abortion, we have used the scheme proposed by Calman in 1996, outlined in Table 5.1.74 While preparing this guideline update, we identified a review article on long-term physical and psychological health consequences of induced abortion, published in 2002.75 This section of the guideline draws heavily on that review.

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The Care of Women Requesting Induced Abortion

Table 5.1 Calman scheme describing degree of risk of complications and sequelae associated with abortion

Term Negligible Minimal Very low Low Moderate High Degree of risk < 1 in 1 000 000 1 in 1 000 000 to 1 in 100 000 1 in 100 000 to 1 in 10 000 1 in 10 000 to 1 in 1000 1 in 1000 to 1 in 100 > 1 in 100

RECOMMENDATION 16.1

B The risk of haemorrhage at the time of abortion is low. It complicates around 1 in 1000 abortions overall. The risk is lower for early abortions (0.88 in 1000 at less than 13 weeks; 4.0 in 1000 at more than 20 weeks).

Evidence supporting recommendation 16.1

The above rates of haemorrhage at the time of abortion are taken from National Office for Statistics abortion statistics76 and represent reports from practitioners in England and Wales via the notification process. Criteria for reporting are ill-defined and it is not known whether or not all these cases required transfusion. Unpublished data from independent abortion providers in the UK suggest overall rates of haemorrhage requiring transfusion of the order of 0.5 in 1000 procedures. In a Danish cohort study, heavy bleeding was registered as a complication in 4.4 in 1000 abortions.77

RECOMMENDATION 16.2

B The risk of uterine perforation at the time of surgical abortion is moderate. The incidence is of the order of 1­4 in 1000. The risk is lower for abortions performed early in pregnancy and those performed by experienced clinicians.

Evidence supporting recommendation 16.2

Evidence table 2 summarises rates of uterine perforation reported in case series that were identified during the development of the previous edition of this guideline. Series for inclusion were selected on the basis of study size (more than 4000 subjects). The more recent Danish cohort study77 (56 117 subjects), published in 2002, reported a rate of uterine perforation of 2.3 in 1000 abortions. A 1999 Australian report78 on 13 907 abortions found a perforation rate of 0.86 in 1000.

RECOMMENDATION 16.3

B Uterine rupture has been reported in association with mid-trimester medical abortion. However, the risk is very low, at well under 1 in 1000.

30

Information for women Evidence supporting recommendation 16.3

Case reports79­82 have described uterine rupture in women undergoing mid-trimester medical abortion. The regimens used varied: mifepristone and misoprostol,79 vaginal misoprostol alone,82 laminaria and misoprostol,80 or misoprostol and oxytocics.81 A retrospective review of over 600 women having mid-trimester abortion, by postaglandin E2, oxytocin, or a combination, suggested that caesarean section is a risk factor for rupture, with an almost 20-fold increase in risk (OR 20.8, 95% CI 14.1­104.00).83 More recent retrospective reviews of women undergoing first and second trimester medical abortion with various regimens have not identified any cases of uterine rupture.84,85

RECOMMENDATION 16.4

B Cervical trauma: the risk of damage to the external cervical os at the time of surgical abortion is moderate (no greater than 1 in 100). The risk is lower when abortion is performed early in pregnancy and when it is performed by an experienced clinician.

Evidence supporting recommendation 16.4

Evidence table 3 summarises incidences of cervical injury during first-trimester surgical abortion, as reported in large case series identified during development of the earlier edition of this guideline. The report from Schulz86 (rate 10.3 in 1000) is based on carefully collected and clearly defined data. The findings are typical of practice in large hospitals in the USA in the mid-1970s and of the results obtained when a significant proportion of the operators were trainees. The rate observed by Ferris42 (0.7 in 1000) is also based on well-organised data collection and may be more typical of today's practice. The 100-fold range in the evidence in Evidence table 3 reflects the lack of an agreed definition of cervical injury and substandard data collection. Cervical injury is more frequent with D&E in the second trimester. The 2002 Danish cohort study77 identified 50 cases of cervical injury among 56 117 abortions (0.89 in 1000).

RECOMMENDATION 16.5

B Failed abortion and continuing pregnancy: all methods of first-trimester abortion carry a small risk of failure to terminate the pregnancy, thus necessitating a further procedure. The risk for surgical abortion is around 2.3 in 1000 and for medical abortion between 1 and 14 in 1000 (depending on the regimen used and the experience of the centre).

Evidence supporting recommendation 16.5

The quoted rate of failure from the Kaunitz study of 33 090 cases when suction termination was performed at 12 weeks or below was 2.3 per 1000 abortions.87 The rate was increased for multiparous women, for abortions at 6 weeks or below, or when small cannulae were used. Other risk factors were: if the procedure was performed by a junior, or if the woman had uterine abnormalities. In the 2002 Danish series of surgical abortions, the rate of `re-evacuation not caused by bleeding' was 5.3 in 1000 (no information was provided as to the proportion of these required for continuing pregnancy).77 For mifepristone and misoprostol medical abortions at gestations up to 63 days, a series of 2000 cases quoted surgical intervention being needed in 2.5% (1.4% for incomplete abortion, 0.4% for

31

The Care of Women Requesting Induced Abortion

missed abortion, 0.6% for continuing pregnancy and 0.2% to exclude ectopic pregnancy).88 An update on this series (4132 cases) was published in 2002.89 Overall, the continuing pregnancy rate was 0.3% but was only 0.1% in 2131 women managed using a modified regimen (discussed in Chapter 7 of this guideline). A series of 3161 mifepristone and gemeprost medical abortions at gestations up to 63 days had a continuing pregnancy rate of 1.4%.90 Kahn et al.91 have published a meta-analysis on efficacy of medical abortion. They provide `viable pregnancy' rates for various medical abortion regimens and various gestation bands. For the midgestation band (50­56 days) the summary viable pregnancy rate for the mifepristone and misoprostol regimens is calculated as 2.6% and for mifepristone with other prostaglandins regimen 2.9%. A comparative review of medical and surgical methods for early abortion quoted continuing pregnancy rates of 0.9% for mifepristone/misoprostol abortion and 0.5% for vacuum aspiration.92

RECOMMENDATION 16.6

B Post-abortion infection: genital tract infection, including pelvic inflammatory disease of varying degrees of severity, occurs in up to 10% of cases. The risk is reduced when prophylactic antibiotics are given or when lower genital tract infection has been excluded by bacteriological screening.

Evidence supporting recommendation 16.6

Genital tract infection, including pelvic inflammatory disease, is a recognised complication of abortion. Incidence rates among the control groups in trials of prophylactic antibiotics for abortion suggest that infective complications occur in up to 10% of cases.93­98 Post-abortion infection may result in the long-term sequelae of tubal infertility or ectopic pregnancy,93 as well as causing morbidity in the immediate post-abortion period. Studies have shown that the presence of Chlamydia trachomatis, Neisseria gonorrhoea99­101 or bacterial vaginosis102,103 in the lower genital tract at the time of abortion is associated with an increased risk. The 2002 Danish cohort study on short-term complications of surgically induced abortions reported a rate of infective complications of only 12 in 1000.77 However, this study included only those complications evident before the woman left hospital following her abortion.

RECOMMENDATION 16.7

B Breast cancer: induced abortion is not associated with an increase in breast cancer risk.

Evidence supporting recommendation 16.7

The evidence considered by the Guideline Development Group regarding breast cancer risk focused on two carefully conducted meta-analyses.104,105 These two reviews reached different conclusions about the nature of any association. The first systematic review, by Wingo et al.,104 was included in the Cochrane Database of Reviews of Effectiveness and met the quality criteria required by the Cochrane group. The review included 28 case­control and cohort studies. Although four studies found that the association between breast cancer and induced abortion reached statistical significance, the authors felt that a definitive conclusion could not be reached because of inconsistent findings across studies. The conflicting review by Brind et al.105 examined the same studies and concluded that induced abortion was a significant, independent risk factor for breast cancer, with an odds ratio of 1.3. (95% CI 1.2­1.4) These two meta-analyses were independently

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Information for women

assessed for the previous edition of this guideline. The methodological assessor concluded that both were carefully conducted reviews and that the Brind et al. study105 had no major methodological shortcomings and could not be disregarded. The subsequent review on long-term physical and psychological consequences of induced abortion by Thorp et al.75 included consideration of breast cancer risk. This review summarised four previous reviews,104­107 including those by Wingo et al.104 and Brind et al.105 While acknowledging the methodological shortcomings of the studies included and the potential influence of the moral values of individual reviewers, Thorpe et al.75 concluded that a significant positive association between induced abortion and breast cancer could not easily be dismissed because the only quantitative review (by Brind et al.105) found a significant positive association (OR 1.3, 95% CI 1.2­1.4). In August 2003, the American College of Obstetricians and Gynecologists (ACOG) published a Committee Opinion Paper on induced abortion and breast cancer risk.108 ACOG summarised the findings of the most methodologically rigorous of the previously reviewed studies (cohort rather than case­control studies and those based on linkage of registry data, rather than women's selfreports) and showed a slight reduction in breast cancer risk associated with past abortion. ACOG also reviewed four studies published since 2000109­112 and the summary report of a National Cancer Institute workshop on early reproductive events and breast cancer, held in March 2003.113 The National Cancer Institute concluded that "induced abortion is not associated with an increase in breast cancer risk", giving this statement a `strength of evidence' rating of 1 (well established). The ACOG Committee on Gynecologic Practice concluded, "Rigorous recent studies argue against a causal relationship between induced abortion and a subsequent increase in breast cancer risk". Evidence table 5 summarises studies relating to induced abortion and breast cancer published since 1999. The table includes those studies reviewed by ACOG in reaching its committee opinion. NOTE: As this guideline was going to press, a major systematic review was published which lent further support to these conclusions.114

RECOMMENDATION 16.8

B Future reproductive outcome: there are no proven associations between induced abortion and subsequent ectopic pregnancy, placenta praevia or infertility. Abortion may be associated with a small increase in the risk of subsequent miscarriage or preterm delivery.

Evidence supporting recommendation 16.8

Studies relating to abortion and future reproductive outcomes identified during development of the previous edition of this guideline are summarised in Evidence table 6. Women with a previous induced abortion appeared to be at an increased risk of infertility in countries where abortion is illegal but not in those where abortion is legal. Published studies strongly suggested that infertility is not a consequence of uncomplicated induced abortion.115­117 There are some discrepancies among studies118 but none of these studies was of sufficient power to detect a small association. There was a similar lack of consensus over the effect of previous induced abortion on rates of preterm delivery. Two studies119,120 found an association, while two others121,122 failed to do so. Most studies focusing on complications associated with abortion by dilatation and evacuation assessed the safety of the procedure, and none looked at the effect on future reproductive outcome. The earlier edition of this guideline stated that there was no conclusive evidence to support an association between induced abortion and infertility or preterm delivery. However, it may be that there is an association between

33

The Care of Women Requesting Induced Abortion

induced abortion complicated by pelvic infection and tubal infertility. Such an association is more likely in cases complicated by uterine perforation or abdominal surgery to repair uterine injury, which may result in peritubal adhesions (or the loss of the uterus). The 2002 review on long-term physical and psychological consequences of induced abortion by Thorp et al.75 provides an update on relationships between abortion and a range of subsequent adverse reproductive outcomes. Miscarriage Thorp et al. reviewed two cohort and three case­control studies examining associations between induced abortion and miscarriage. None found a significant association. Moreover, those that analysed data according to the number of abortions found no dose­response effect. More recent studies identified during development of this updated guideline have, however, reported less reassuring findings. A Danish study showed an increased risk of miscarriage among women who became pregnant within three months of an abortion.123 A cohort study from Shanghai included 2953 pregnant women: 1502 whose previous pregnancy was terminated by vacuum aspiration and a reference cohort of 1451 primigravidae.124 After adjustment, the odds ratio for first-trimester miscarriage between the `abortion' and `reference' cohorts was 1.72 (95% CI 1.09­2.72). Preterm birth Thorp et al. appraised ten case­control and 14 cohort studies relating to abortion and subsequent preterm birth or low birth weight. Twelve of the studies showed a positive association and seven showed a dose­response effect. Thorp et al. highlighted the fact that large, recent cohort studies based on register linkage consistently show a positive association. More recent studies identified during development of this guideline update have reported mixed findings. A French cohort study125 involving 12 432 women suggested that "a history of induced abortion increases the risk of preterm delivery, particularly for women who have had repeated abortions". A small Swedish case­control study126 involved 312 cases of preterm birth and 424 controls who delivered at term. A history of two or more induced abortions was not associated with preterm birth, whereas a history of two or more miscarriages was. Among those studies that suggest a significant association between abortion and preterm birth, the elevation in risk ratio is between 1.3 and 2.0. Placenta praevia Thorp et al. reviewed one cohort and two case­control studies examining associations between induced abortion and subsequent placenta praevia. All found a positive association. They also appraised a meta-analysis of observational studies on abortion and placenta praevia. These studies were of variable quality and showed substantial heterogeneity but again showed a positive association. More recent studies identified during development of this guideline update have, however, reported more reassuring findings. A Danish cohort study based on national registry data linkage involved 15 727 women whose first pregnancy was terminated and a reference cohort of 46 026 women.127 No association with placenta praevia was seen. A case­control study from the USA involved 192 cases of placenta praevia and 622 controls.128 The investigators concluded that risk of placenta praevia might have increased in a dose­response fashion with sharp curettage abortions, but that vacuum aspiration did not confer an increased risk.

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Information for women

Ectopic pregnancy Thorp et al. reviewed seven case­control and two cohort studies relating to abortion and subsequent ectopic pregnancy. Only two of the nine studies reported a positive association; these were relatively small case­control studies which relied on self-report of previous abortion. Large studies based on record linkage showed no association. Subfertility Thorp et al. appraised three case­control and four cohort studies relating to abortion and subfertility. Two relatively small case­control studies, both from Greece, showed a positive association. Other studies found no association. Thorp et al. commented on methodological limitations of all studies. All studies reviewed by Thorp et al. date from before 1999. No relevant new studies were identified during the update literature search.

RECOMMENDATION 16.9

B Psychological sequelae: some studies suggest that rates of psychiatric illness or self-harm are higher among women who have had an abortion compared with women who give birth and to nonpregnant women of similar age. It must be borne in mind that these findings do not imply a causal association and may reflect continuation of pre-existing conditions.

Evidence supporting recommendation 16.9

The view of the Guideline Development Group on this topic was largely based on a review undertaken by Dagg.129 He reviewed the existing literature in relation to both the psychological sequelae of abortion and the sequelae for the mother and the child when abortion was denied. He concluded: "Adverse sequelae occur in a minority of women, and when such symptoms occur, they usually seem to be the continuation of symptoms that appeared before the abortion and are on the wane immediately after the abortion. Many women denied abortion show ongoing resentment that may last for years". In preparing this update, we studied a more recent review by Thorp et al.75 We independently reviewed the studies cited in that paper and also more recently published studies. The most robust and sizeable of these studies are summarised in Evidence table 7. Note, however, that four of these six studies were undertaken in countries with much higher underlying suicide rates than those seen in the UK.

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Chapter 6

Pre-abortion management

6.1 The abortion decision

RECOMMENDATION 17

C Clinicians caring for women requesting abortion should try to identify those who require more support in decision making than can be provided in the routine clinic setting (such as those with a psychiatric history, poor social support, or evidence of coercion). Care pathways for additional support, including access to social services, should be available.

Evidence supporting recommendation 17

This guideline has been developed for clinicians working in abortion services and relates to the care of women requesting induced abortion. Women will have received varying degrees of pregnancy counselling and support prior to attendance at an abortion service and will vary in their degree of certainty about the abortion decision. All women attending an abortion service will require discussion of the implications of their intended course of action and will require support in reaching their final decisions and choices. Abortion service professionals must be sensitive to the different stages of decision making that individual women have reached, and must be able to provide the degree of support and counselling required by each individual. The Guideline Development Group favoured the use of the term `support' rather than `counselling' to describe these routine responsibilities of an abortion service, but acknowledged that any of three recognised forms of counselling may be required by women considering or undergoing induced abortion. For the minority of women who require formal, therapeutic counselling, services should have formal care pathways in place with access to trained counsellors with appropriate expertise. A review from the American Psychological Association130 has summarised the literature on factors associated with negative responses to abortion and with difficulties in decision making. Counselling has been defined as, "the process of enhancing a subject's ability to assess and understand the index situation, evaluate options and make an informed choice or decision. This entails sensitive provision of comprehensive information in a nondirective or nonjudgmental manner".131 The provision of counselling is viewed as an essential element of fertility regulation services.131 The HFEA Code of Practice132 identifies three different types of counselling, all of which are to be regarded as distinct from simple information exchange: Implications counselling: Support counselling: aims to enable the person concerned to understand the implications of the proposed course of action for themselves and for their family. aims to give emotional support at times of particular stress.

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Pre-abortion management

Therapeutic counselling: aims to help people with the consequences of their decision and to help them resolve problems which may arise as a result.

6.2 Blood tests

RECOMMENDATION 18

C Pre-abortion assessment should include: · measurement of haemoglobin concentration · determination of ABO and rhesus blood groups with screening for red cell antibodies · testing for other conditions such as haemoglobinopathies, HIV, and hepatitis B and C if indicated in the light of clinical features, individual risk factors or local prevalence.

Evidence supporting recommendation 18

A Health Technology Assessment systematic review,133 looking at routine preoperative testing, found that haemoglobin was lower than 10.0­10.5 g/dl in less than 5% of patients. In 2003, NICE published a guideline on the use of routine preoperative tests for elective surgery.134 Recommendations relating to full blood count were consensus-based, in view of a lack of directly relevant evidence. NICE did not recommend routine full blood count for adults undergoing `intermediate' surgical procedures. Nevertheless, due to the nature of surgical abortion and the possibility of excessive blood loss, routine haemoglobin estimations are recommended by both the Guideline Development Group and the Update Group. The `group and screen' procedure undertaken by the blood transfusion service laboratories should include not only ascertainment of the woman's ABO and rhesus blood groups, but also screening for IgG antibodies that can damage red blood cells at 37°C. Ascertainment of rhesus group is required in order that Anti-D prophylaxis can be instituted as appropriate. Screening for red cell antibodies is required to alert staff to any difficulties that may be encountered should subsequent crossmatching and blood transfusion be required. In the previous edition of this guideline, screening for hepatitis and HIV were recommended on a selective basis, as was testing for haemoglobinopathies. The routine offer of testing for HIV as part of antenatal care was introduced in 1999 and the offer of HIV testing to all new attenders at genitourinary medicine clinics is a component of the 2001 National Strategy for Sexual Health and HIV.8 These initiatives have prompted discussion in a number of quarters about the appropriateness of offering HIV testing routinely to abortion attenders. A study published in 1999 examined patients' attitudes to HIV testing in five north London abortion clinics.135 Data were cited indicating that HIV prevalence was up to three times higher in women seeking abortion, compared with women seeking antenatal care (2002 data from the Department of Health relating to inner London showed an HIV prevalence of 1 in 108 among abortion attenders and of 1 in 171 among antenatal attenders). An attitude survey indicated that around 70% of abortion attenders would welcome discussion about HIV and counselling regarding testing. Local abortion service protocols should include policies on the offering of HIV tests. Local policies should take account of local prevalence of HIV and resource constraints. Where services choose to offer HIV testing in the context of abortion care, local protocols must ensure that valid consent is obtained for this specific element of care.

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The Care of Women Requesting Induced Abortion

It may be appropriate to offer immunisation to women at high risk of hepatitis B, regardless of the results of pre-abortion testing. High-risk groups include intravenous drug users and sex workers. When managing such patients, abortion service staff should seek guidance from their local virology department regarding the need for immunisation and the appropriate vaccine course.

RECOMMENDATION 19

B It is not cost effective routinely to crossmatch women undergoing induced abortion.

Evidence supporting recommendation 19:

Figures supplied by the abortion charity bpas indicated that in 1998 only 0.2% of clients required blood transfusion. The Guideline Development Group was of the view that this rate of transfusion was of the same order as that found in the NHS sector. The group concluded that it is not cost effective to request crossmatched blood routinely for women undergoing abortion. In most NHS abortion services, a blood bank is available on site and it was felt that the most cost effective strategy for those instances where blood transfusion is required is simply to initiate crossmatching on the basis of a newly submitted specimen of the woman's blood, as and when the need arises. When abortion is undertaken in settings that are remote from a blood bank, policies of saving women's serum at the blood bank and the availability of O Rh-negative blood at the abortion centre may be considered for inclusion in local protocols. In developing local protocols, services must include contingency plans for the very small number of women, usually at 15 weeks of gestation or beyond, experiencing life-threatening haemorrhage. In about 50% of these, haemorrhage will be associated with disseminated intravascular coagulation. For independent abortion clinics, these protocols must include arrangements for transfer to a specialist acute hospital.

6.3 Cervical cytology

RECOMMENDATION 20

Assessment prior to induced abortion may be viewed as an opportunity to ascertain each woman's cervical cytology history. Women who have not had a cervical smear within the interval recommended in their local programme may be offered one within the abortion service.

RECOMMENDATION 21

If a cervical smear is taken within the abortion service, then mechanisms are essential to ensure that the smear result is communicated to the woman, acted on appropriately and recorded within the local cervical cytology programme.

Evidence supporting recommendations 20 and 21

Within a spirit of providing holistic care, clinicians may view a woman's attendance within an abortion service as an opportunity to review broader aspects of her reproductive health care. Offering to undertake cervical cytology for any woman who has not had a cervical smear taken

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Pre-abortion management

within the interval recommended within her local programme represents one such aspect of health care (it should be noted that women aged under 20 years need not be offered screening, as national cytology programmes begin at age 20 years). The Guideline Development Group were of the view that, particularly where abortion care is provided within the NHS in the woman's local gynaecology unit, then expansion of the role of the abortion service to embrace these broader aspects of care is appropriate. However, the group also felt that offering cervical cytology should not be considered an essential function of an abortion service. Indeed, where abortion services are provided through agency arrangements with charitable sector providers, the service might lack appropriate mechanisms for ensuring that results of cytology are followed up appropriately.

6.4 Ultrasound scanning

RECOMMENDATION 22

B All services must have access to scanning, as it can be a necessary part of pre-abortion assessment, particularly where gestation is in doubt or where extrauterine pregnancy is suspected. However, ultrasound scanning is not considered to be an essential prerequisite of abortion in all cases.

RECOMMENDATION 23

C When ultrasound scanning is undertaken, it should be done in a setting and manner sensitive to the woman's situation. It is inappropriate for pre-abortion scanning to be undertaken in an antenatal department alongside women with wanted pregnancies.

Evidence supporting recommendations 22 and 23

During the triennium 1994­96, one death as a direct consequence of a legal abortion was reported through the Confidential Enquiries into Maternal Deaths in the UK (CEMD).136 On the basis of this one case, the CEMD report recommends: "Ideally, all women should undergo ultrasound examination before termination of pregnancy to establish gestational age, viability and site". In the 1997­99 triennium, two deaths followed termination of pregnancy. Neither was directly attributable to the surgical procedure and no recommendations were made relating to the care of women undergoing induced abortion.137 The Guideline Development Group was of the view that, while ultrasound may be useful in preabortion assessment, its use was not mandatory in all cases. However, abortion services must have access to appropriate ultrasound facilities for those women for whom scanning is clinically indicated. A literature search by the Guideline Development Group failed to identify any randomised trials relating to the value of ultrasound prior to abortion. The recommendations were therefore based on evidence from the observational studies summarised here. Goldstein et al.138 studied 250 consecutive pregnancies at 12 weeks of gestation or less. In 1.6% (four cases) the gestational age assessed by ultrasound was greater than 12 weeks and the women were referred for alternative methods of abortion. The study does not demonstrate whether or not clinical examination would have also detected the discrepancies. Kaali et al.139 reported a before-and-after study to evaluate the benefits of adding routine ultrasonography to their abortion protocol. These authors concluded that adding ultrasonography (plus semiquantitative serum hCG testing) to their earlier protocol streamlined care and reduced the number of clinic visits. Burnhill and Armstead140

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The Care of Women Requesting Induced Abortion

reported on their experience with over 7000 first-trimester abortions and concluded that routine use of ultrasound `when gestational age is unclear' is an essential measure in reducing the incidence and severity of abortion complications. Two studies identified during development of this guideline update compared ultrasound assessment with clinical examination in the context of abortion care. A study from the USA141 included 1016 women seeking medical abortion. Before women underwent ultrasound scanning, experienced clinicians assessed gestation using a combination of clinical history and bimanual pelvic examination. Clinicians correctly assessed gestational age as no more than 63 days in 87% of women. In only 1% of their assessments did clinicians underestimate gestational age (that is, assess women as under 63 days when they were actually greater than 63 days), which might have increased the woman's chance of failure of medical abortion and requirement for surgical intervention. The investigators concluded that "medical abortion can be safely performed without sonography". A second US study compared clinical gestation assessments by both experienced (faculty) and inexperienced (resident) clinicians with ultrasound assessments in 245 women.142 Even when examined by the faculty gynaecologist, 8% of women had clinical estimates that differed by more than 2 weeks from the ultrasound assessment (clinical gestation was an overestimate in 3.7% and an underestimate in 4.5%). The authors argued that a discrepancy in either direction might cause problems during surgical abortion in terms of unnecessarily excessive or inadequate cervical dilatation. The 2000 guideline recommendation that "when ultrasound scanning is undertaken, it should be done in a setting and manner which are sensitive to the woman's situation" was based on previous guidance documents and the consensus view of the Guideline Development Group. A study from South Africa, published in 2002, examined the clinical usefulness of ultrasound before termination and the consequences for women of visualisation or non-visualisation of ultrasound images.143 Five hundred women being scanned prior to abortion were randomly allocated to having the ultrasound screen turned away or in its normal position. This study had a number of methodological problems, but indicated that the scan produced `clinically useful' information in only 3% of cases. However, when asked about their preferences both immediately after the abortion and 6­12 weeks later, the majority of women (over 90% immediately post-abortion) favoured having a scan prior to an abortion. The majority of these women favoured a scan `with visualisation' of the image. Thus, in trying to provide ultrasound `in a manner which is sensitive to the woman's situation', clinicians should not assume that the image should be concealed.

6.5 Prevention of infective complications

RECOMMENDATION 24

A B Abortion care should encompass a strategy for minimising the risk of post-abortion infective morbidity. As a minimum, services should offer antibiotic prophylaxis. Ideally, services should offer testing for lower genital tract organisms with treatment of positive cases.

40

Pre-abortion management RECOMMENDATION 25

C The following regimens are suitable for periabortion prophylaxis: · metronidazole 1 g rectally at the time of abortion plus · doxycycline 100 mg orally twice daily for 7 days, commencing on the day of abortion OR · metronidazole 1 g rectally at the time of abortion plus · azithromycin 1 g orally on the day of abortion.

Evidence supporting recommendation 24 and 25

Genital tract infection, including pelvic inflammatory disease, is a recognised complication of abortion. Incidence rates among the control groups in trials of prophylactic antibiotics for abortion suggest that infective complications occur in up to 10% of cases.93­98 Post-abortion infection may result in the long-term sequelae of tubal infertility or ectopic pregnancy,93 as well as causing morbidity in the immediate post-abortion period. Studies have shown that the presence of C. trachomatis, N. gonorrhoea99­101 or bacterial vaginosis102,103 in the lower genital tract at the time of abortion is associated with an increased risk. Level Ia evidence from a meta-analysis of randomised trials published by Sawaya et al.144 demonstrated that the use of antibiotic prophylaxis at the time of abortion was associated with a reduction in the risk of subsequent infective morbidity by around 50%. Other authors have argued that bacteriological screening of the lower genital tract before abortion, with treatment of those found to be carrying genital tract organisms, would be a more appropriate strategy.94,99­103 In England and Wales at present, some regions are participating in Chlamydia screening programme rollout exercises. In these regions, all women aged under 25 years should be offered Chlamydia screening as part of the programme. Blackwell et al.145 advocate a third strategy, a `belt and braces' approach, whereby all women undergoing abortion receive a prophylactic regimen effective against bacterial vaginosis and Chlamydia but are also screened for sexually transmitted infections (gonorrhoea and Chlamydia). This strategy combines the benefits of the other two approaches ­ but also combines the costs. Penney et al.146 compared prophylaxis and a 'screen and treat' strategy in terms of both clinical and cost effectiveness in a randomised trial. Using a formal costing methodology, they quantified the relevant costs to the NHS of instituting one or other strategy. The primary outcomes measured were the prevalence of post-abortion infective morbidity as assessed by the general practitioner, prescription rates and hospital reattendances. 1672 women were recruited. The prevalence of C. trachomatis was 5.6%, N. Gonorrhoea, 0.19%, and bacterial vaginosis, 17.5%. The results indicated that universal prophylaxis can be provided at a cost of less than 50% that of screening with treatment and follow-up of positive cases. This study suggested that universal prophylaxis was at least as effective as a policy of `screen and treat' in minimising short-term infective sequelae of abortion and could be provided at less cost. The Guideline Development Group was of the view that all abortion services should have in place some form of strategy for reducing the risk of post-abortion infective sequelae. As a minimum, this should comprise antibiotic prophylaxis effective against both C. trachomatis and bacterial vaginosis. The group also considered that, where resources permit and provided that it is acceptable

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The Care of Women Requesting Induced Abortion

to women and their partners, services may offer screening for sexually transmitted infections, with follow-up and partner notification for positive cases. In developing this guideline update, we identified seven studies directly addressing the prevention of infective complications of abortion. Three publications described clinical trials of prophylactic antibiotic regimens. A Scandinavian randomised, double-blind, placebo-controlled trial involving 1655 women evaluated the efficacy of preoperative treatment with clindamycin cream in reducing post-abortion infective morbidity.147 Based on microscopy of vaginal smears, 20% of subjects had bacterial vaginosis and a further 13% had `intermediate flora'. In these two groups combined, treatment with clindamycin cream reduced the incidence of infective morbidity by a factor of four. A UK randomised, double-blind, placebo-controlled trial evaluated the efficacy of rectal metronidazole in reducing post-abortion infective morbidity in women with bacterial vaginosis.148 Based on microscopy of vaginal smears, 29% of women attending this abortion service had bacterial vaginosis. The trial involved 273 women who tested positive. The study indicated that perioperative metronidazole might reduce the risk of infective morbidity by a factor of two; however, the study had limited power and the finding was not statistically significant. A randomised trial involving 800 women compared regimens of 7 days and 3 days of doxycycline (100 mg twice daily) for peri-abortion prophylaxis.149 The investigators concluded that shortening oral doxycycline prophylaxis from 7 to 3 days had no adverse effect on the incidence of post-abortal infection. In this trial, 44% of subjects were lost to followup, the study had limited power and the authors concluded that further trials were needed to enable their findings to be applied more generally. Four publications described case series or local experience relating to the implementation of `screen and treat' strategies in clinical practice. A UK (Stevenage) study aimed to assess the relative benefits of testing for C. trachomatis or universal antibiotic prophylaxis in an abortion service.150 The investigators describe a series of 100 women tested for C. trachomatis prior to abortion. Six were positive. Nine sexual partners were identified, of which four were positive for C.trachomatis. On the basis of this series, the investigators argued that prophylaxis would be a waste of resources, as 94% of women would have been treated unnecessarily, and women positive for C. trachomatis would be reinfected by their untreated partners. A broadly similar UK (Sheffield) study assessed the value of a `screen and treat' policy by review of 100 consecutive Chlamydia-positive women identified within an abortion service.151 Of these, 72 attended a follow-up genitourinary clinic appointment; 89 sexual partners were notified and 62 attended for treatment. The investigators concluded that their experience showed the relative success of a `screen and treat' policy, which may confer greater benefit for women and make a significant impact on the reservoir of infection in the community. A further UK (Nottingham) study described experience with implementing a `screen and treat' policy.152 The investigators described the journey of care for 40 women testing positive for C. trachomatis or N. gonorrhoeae managed by their local strategy. Within this model of care, the genitourinary medicine service is notified of positive cases directly by the microbiology laboratory, women are contacted directly by the genitourinary medicine service and treatment instituted, ideally prior to the abortion. Only two of 31 women who proceeded to abortion had been treated adequately before or at the time of abortion. The investigators concluded that it was essential to organise services so that treatment could be given before surgical intervention. The final UK (Edinburgh) publication was entitled Can a busy abortion service cope with a screen-and-treat policy for chlamydia trachomatis infection?.153 In a series of 2058 patients, the prevalence of C. trachomatis was 6%. Positive results were available before surgical abortion for 97% and before medical abortion for 76%. Most women (94% surgical; 84% medical) were seen at the genitourinary medicine clinic but only 25% of notified partners attended. The authors reflected on the deficiencies of their current strategy and on the resource implications of possible solutions.

42

Pre-abortion management

Evidence to support specific antibiotic regimens for periabortion prophylaxis remains scant. The Guideline Update Group considers that the chosen regimen should cover both anaerobic vaginosis and C. trachomatis. The doxycycline and azithromycin regimens suggested here are those recommended in manufacturers' summaries of product characteristics for treatment (rather than prophylaxis) of uncomplicated chlamydial infections.154,155 An updated guideline from the US National Abortion Federation recommends antibiotics at the time of surgical abortion but does not suggest a specific regimen.156 Recent UK157 and US158 guidelines on the management of victims of sexual assault recommend either the 7-day doxycycline regimen or the immediate-dose azithromycin regimen for prophylaxis in that context. The recommended regimens suggested here are those with which the guideline developers have experience. Other regimens may be equally appropriate.

6.6 Feticide prior to late abortions

The RCOG's 1996 guidance on termination of pregnancy for fetal abnormality emphasised that a legal abortion must not be allowed to result in a live birth.4 Theoretically, such an event could result in a doctor being accused of murder if a `deliberate act' (that is, legal abortion) were to be followed by a live birth and the subsequent death of the child because of immaturity. The same document included the guidance that for "terminations after 21 weeks, the method chosen should ensure that the fetus is born dead". Very few abortions on grounds `C' or `D' are undertaken at such gestations. Those few are, for the most part, undertaken within the specialist independent sector. When the method of abortion chosen is surgical (D&E) by a specialist practitioner, the nature of the procedure ensures that there is no risk of a live birth. When medical abortion is chosen, then special steps are required to ensure that the fetus is dead at the time of abortion. An Appendix to the RCOG's Termination of Pregnancy for Fetal Abnormality report summarises the available methods.4 A more recent RCOG Statement has summarised additional sources of information on late abortion and feticide.6 A retrospective case series from the USA is of interest. It demonstrated that feticide with potassium chloride significantly reduced the prostaglandin requirement for mid-trimester medical abortion, compared with similar procedures conducted without feticide.159

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Chapter 7

Abortion procedures

Abortion on grounds relating to the physical or mental health of the mother or of her existing children can be performed within the law at gestations up to 24 weeks. At all gestations up to this limit, abortion can be performed by either surgical or medical (that is, by means of drugs) methods. Depending on the gestation at which a woman presents for abortion, different abortion techniques are appropriate. Figure 7.1 summarises those abortion methods considered by the Guideline Update Group to be appropriate for use in UK abortion services for women presenting in different gestation bands. As this guideline focuses on abortion for maternal health reasons, methods for abortion beyond 24 weeks are not discussed. Such procedures would usually be undertaken on the grounds of fetal abnormality, and lie outwith the scope of this guideline. General recommendations about abortion procedures are discussed first, followed by recommendations relating to specific techniques.

RECOMMENDATION 26

As a minimum, all services should be able to offer abortion by one of the recommended methods for each gestation band.

RECOMMENDATION 27

B Ideally, abortion services should be able to offer a choice of recommended methods for each gestation band.

Evidence supporting recommendations 26 and 27

The Guideline Development and Update Groups view induced abortion as a healthcare need. They therefore consider that services for a population should be able to provide abortion, by at least one recommended method, for women at any gestation at which abortion is permitted within the law. Abortion late in the second trimester is uncommon and requires special expertise and particular staff attitudes. For many services, it may be appropriate for late abortions to be provided through agency arrangements with the specialist charitable sector providers. Level III evidence from a number of patient surveys confirms that women value being offered a choice of methods appropriate to the gestation at which they present.160­162

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Abortion procedures

7.1 Surgical methods of abortion

Surgical abortion in very early pregnancy RECOMMENDATION 28

B Conventional suction termination should be avoided at gestations below 7 weeks.

Gestation (weeks from date of last menstrual period)

4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Medical abortion using 1 mifepristone and prostaglandin

Medical abortion using mifepristone and multiple doses of prostaglandin 2

Surgical abortion by dilatation and evacuation by specialist practitioners 5 Early aspiration abortion to strict protocol 3

Suction termination under general or local anaesthetic 4

1 Medical abortion using a single oral dose of the anti-progesterone, mifepristone, followed by a single dose (vaginal or oral) of prostaglandin (also known as pharmacological or non-surgical abortion). 2 Medical abortion using a single oral dose of the anti-progesterone, mifepristone, followed by multiple doses (vaginal or oral) of prostaglandin (also known as pharmacological or nonsurgical abortion). 3 Surgical abortion by means of suction aspiration (using electric or manual suction) at gestations below 7 weeks. To increase confidence that the gestation sac has been removed, protocols include safeguards such as magnification of aspirate and follow-up serum hCG estimation. 4 Conventional suction termination using electric or manual suction, under general or local anaesthetic. The uterus is emptied using a suction curette. Sharp curettage with metal instruments is not employed. 5 Surgical abortion at later gestations using a combination of suction (usually electric) curettage and specialised forceps.

Figure 7.1 Summary of abortion methods appropriate for use in UK abortion services for women presenting in different gestation bands

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The Care of Women Requesting Induced Abortion Evidence supporting recommendation 28

Suction terminations performed at less than 7 weeks of gestation are three times more likely to fail to remove the gestational sac than those performed between 7 and 12 weeks (level IIb evidence).87 Thus, for women presenting at less than 7 weeks of gestation, an alternative recommended technique should be chosen. If conventional suction termination is the only method of abortion available within a service, then the procedure is better deferred until the pregnancy exceeds 7 weeks of gestation.

RECOMMENDATION 29

B Early surgical abortion using a rigorous protocol (which includes magnification of aspirated material and indications for serum hCG follow-up) may be used at gestations below seven weeks, although data suggest that the failure rate is higher than for medical abortion.

Evidence supporting recommendation 29

Creinin and Edwards have described a personal series (level III evidence) of early surgical abortions undertaken to a rigorous protocol developed at Planned Parenthood of Houston and Southeast Texas, USA.163 Their protocol included pre-abortion urinary pregnancy testing and ultrasound assessment, inspection under magnification of aspirated products and follow-up by serum hCG estimation in those women in whom no gestation sac is verified in the aspirate. Using this protocol, the authors reported a complete abortion rate of over 99% in 2399 procedures performed at less than six weeks of gestation. Both major UK abortion charities (bpas and Marie Stopes International) have introduced early surgical abortion techniques within their UK clinics. bpas has introduced a protocol that conforms to that described above, using local anaesthesia. Marie Stopes International has introduced manual vacuum aspiration (MVA) without anaesthesia. Low failure rates and high patient acceptability are reported (J Murty, oral presentation RCOG/FFPRHC Medical Gynaecology Meeting 1999). The Guideline Development Group was unable to identify any randomised controlled trials comparing such surgical techniques for very early abortion with contemporary methods of medical abortion. A number of randomised trials have compared historical prostaglandin-only medical abortion regimens with vacuum aspiration.164­168 The results of these studies did not strongly favour either method. In developing this edition of the guideline, the Guideline Update Group identified a randomised comparison of medical abortion using methotrexate and misoprostol versus manual vacuum aspiration under local anaesthesia for pregnancies up to 49 days of gestation.169 This small study of 50 women did not have the power to determine differences in efficacy. Among those women who did not initially have a strong preference between medical and surgical abortion, however, the side effect profile and acceptability were significantly better for surgical, compared to medical, abortion. The Planned Parenthood Federation of America has published a case series of 1132 surgical abortions undertaken at less than 6 weeks of gestation in three of their clinics.170 Among women who were followed up at 2 weeks, the continuing pregnancy rate was 2.3%. This is higher than the rate of 0.13% reported by Creinin and Edwards163 in their personal series of surgical abortions undertaken at less than 6 weeks of gestation, and higher than the rate of 0.1% among women at less than 49 days of gestation reported by Ashok et al. in a UK series of early medical abortions.89 In view of this finding, the Guideline Update Group advises that very early surgical abortion should be used only with caution in UK practice.

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Abortion procedures

A small randomised trial has investigated the usefulness of a specially lubricated cannula for early surgical abortion.171 Results were inconclusive and no recommendation can be made.

Suction termination RECOMMENDATION 30

B Conventional suction termination is an appropriate method at gestations of 7­15 weeks, although, in some settings, the skills and experience of practitioners may make medical abortion more appropriate at gestations above 12 weeks.

RECOMMENDATION 31

During suction termination, the uterus should be emptied using the suction curette and blunt forceps (if required) only. The procedure should not be completed by sharp curettage.

Evidence supporting recommendations 30 and 31

In current UK practice, suction termination of pregnancy is the standard method at gestations of 9­12 weeks. This was the only method the Guideline Development Group was able to recommend for this gestation band. However, a pilot study had indicated that medical abortion was also effective at these gestations.172 Subsequent studies, discussed below in Section 7.2, have confirmed that both surgical and medical methods are safe, effective and acceptable in this gestation band. It is accepted UK practice that suction curettage is preferable to sharp curettage for surgical abortion. A Cochrane review published in 2001 included only two trials (dating from the 1970s) comparing the two methods.173 There were few statistically significant differences between the methods, but vacuum aspiration was associated with shorter operating times. In routine practice, clinicians differ in the techniques they use to ensure that the uterus has been completely emptied at the end of a suction termination. In the experience of the Guideline Update Group, there is no need to undertake sharp curettage at the end of the suction evacuation. The `gritty' sensation resulting from the completely emptied uterus clamping down around the suction curette provides sufficient assurance. A report of a comparative trial highlighted the risks (including Asherman's syndrome) of sharp curettage and suggested routine intraoperative ultrasound as a means of obviating the need for sharp curettage.174 In the experience of the Update Group, neither procedure is required as a routine. The method of choice at gestations of 12­15 weeks varies according to the skills and experience of local clinicians. The Guideline Development and Update Groups were of the view that surgical abortion by conventional suction termination, without the need for specialised instruments, can be undertaken up to 15 completed weeks of gestation if local clinicians have gained experience with this method. Alternatively, medical abortion using mifepristone and prostaglandin is appropriate at all gestations. A cohort study from Oxford has shown that morbidity after first-trimester abortion is directly related to gestation and inversely related to the seniority of the surgeon.175 This finding suggests that abortion procedures, particularly those at 12 weeks and above, should not be delegated to the most junior team member.

47

The Care of Women Requesting Induced Abortion Anaesthesia for surgical abortion RECOMMENDATION 32

B Suction termination is safer under local anaesthesia than under general anaesthesia. Consideration should be given to making this option available, particularly for low-gestation procedures.

RECOMMENDATION 33

C If conscious sedation is used in place of general anaesthesia to reduce the pain and anxiety associated with surgical abortion, it should be undertaken only by trained practitioners and in line with Department of Health guidance.

Evidence supporting recommendations 32 and 33

In the 1970s, the relative safety of suction terminations performed with either local or general anaesthesia had not been clearly established. To compare the safety of these two anaesthetic techniques a number of observational and partially randomised studies were undertaken. The evidence from three relevant studies that were selected on quality grounds by the Guideline Development Group are shown in Evidence table 8. A more recent study from India examined women's preferences for general or local anaesthesia during first-trimester surgical abortion.176 Given the choice, 60 of 100 women chose general anaesthesia. Women in both local and general anaesthesia groups were satisfied but women who had local anaesthesia were more likely to recommend it to friends. The findings suggested that women see advantages in local anaesthesia and some are willing to accept additional short-term pain in exchange for these advantages. Women and clinicians in the UK are relatively unfamiliar with abortion under local anaesthesia. It is suggested that services choosing to introduce abortion under local anaesthersia might offer this for low-gestation procedures in the first instance. Paracervical block is accepted as standard local anaesthesia for first-trimester surgical abortion. However, the technique for paracervical block itself is not standardised. A randomised trial compared two-point and four-point injection techniques for chloroprocaine and found no difference in pain ratings.177 It has been argued that the use of a local anaesthetic agent is unnecessary and that tissue distension with an inactive agent such as saline would produce the same effect. However, in the same trial, women injected with chloroprocaine reported significantly less pain than others injected with saline. A further randomised trial compared two-point paracervical block with lignocaine and with water.178 Again, the placebo group experienced significantly more pain than the group treated with the active agent. A third trial compared reported pain in women undergoing abortion immediately after three-point paracervical block with lidocaine and in women with a 3­5 minute delay between the paracervical block and the procedure.179 There were no significant differences in pain or satisfaction between the groups. Conscious sedation is used in place of general anaesthesia by some abortion providers, particularly in the charitable sector. Conscious sedation regimens typically include an intravenous opioid (such as fentanyl) plus an intravenous sedative (such as midazolam or propofol). In 2002, the Department of Health published an Expert Group report180 on conscious sedation in termination of pregnancy and, in 2001, the Academy of Medical Royal Colleges published a report, Implementing and

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Abortion procedures

Ensuring Safe Sedation Practice for Healthcare Procedures in Adults.181 The recommendations in these reports must be followed closely by any service choosing to offer conscious sedation. A placebo-controlled, randomised trial evaluated the efficacy of intravenous fentanyl in reducing pain associated with first-trimester suction abortion under paracervical block.182 The use of fentanyl reduced immediate post-abortion pain by one point on an 11-point scale; the investigators questioned the clinical significance of a reduction of this magnitude. A further placebo-controlled randomised trial evaluated intravenous midazolam plus fentanyl for conscious sedation in conjunction with paracervical block for suction abortion up to 12 weeks of gestation.183 There were no statistically significant differences between study groups in pain scores; nevertheless, women in the conscious sedation group reported better satisfaction levels. A further trial, with both randomised and patient preference components, evaluated sedation with oral lorazepam prior to suction curettage under local anaesthetic.184 Use of lorazepam had no objective impact on anxiety or pain scores.

Electric or manual aspiration RECOMMENDATION 34

A For first-trimester suction termination, either electric or manual aspiration devices may be used, as both are effective and acceptable to women and clinicians. Operating times are shorter with electric aspiration.

Evidence supporting recommendation 34

Relevant randomised trials are summarised in Evidence table 9.

Mid-trimester surgical abortion RECOMMENDATION 35

A For gestations above 15 weeks, surgical abortion by dilatation and evacuation (D&E), preceded by cervical preparation, is safe and effective when undertaken by specialist practitioners with access to the necessary instruments and who have a sufficiently large caseload to maintain their skills.

Evidence supporting recommendation 35

In 2002, a retrospective cohort study of 297 women compared the complication rates of D&E and contemporary methods of medical abortion, specifically misoprostol.185 Overall, women who underwent medical abortion were significantly more likely to have a complication than women who underwent D&E (29% versus 4%). Women who underwent medical abortion with misoprostol were less likely to have complications than women who underwent medical abortion using other regimens, but still had more complications than those who underwent D&E (22% versus 4%). The most common complication of medical abortion was retained products of conception requiring surgical evacuation but, even when these were excluded, women who underwent medical abortion still had more complications, including one case of uterine rupture. The use of real-time ultrasound scanning during D&E can reduce the perforation rate. Darney and Sweet studied the value of intraoperative ultrasound between 16 and 24 weeks of gestation,

49

The Care of Women Requesting Induced Abortion

comparing 353 elective abortions performed without ultrasound with 457 in which ultrasound was routinely employed.186 All operations were carried out in the same clinic with the same technique, but subjects were not randomly allocated. The rate of uterine perforation was 0.2% in the scanned group compared to 1.4% in the unscanned. Historically, it has been considered that D&E is a risk factor for subsequent adverse pregnancy outcomes, including cervical weakness, pregnancy loss and preterm birth. A retrospective case series included 600 women who underwent mid-trimester D&E between 1996 and 2000.187 Interpretation of the findings is difficult, as no reference cohort of women who had not undergone D&E was described. Nevertheless, rates of adverse pregnancy outcomes appeared similar to those of unselected populations. The authors concluded that "second-trimester D&E is not a risk factor for mid-trimester pregnancy loss or spontaneous preterm birth". D&E is the standard method at gestations above 15 weeks in the non-NHS abortion service in England, although it has not found general favour among gynaecologists working in the NHS. D&E can be undertaken safely only by gynaecologists who have been trained in the technique, have the necessary instruments and have a caseload sufficient to maintain their skills. For gynaecologists lacking the necessary expertise and caseload, and for their patients, mid-trimester medical abortion using mifepristone plus prostaglandin is appropriate. Published evidence provides reassurance on the safety and efficacy in mid-trimester of both D&E and medical abortion using mifepristone plus prostaglandin. Other methods of mid-trimester abortion have been described. These include: · `intact D&X' (also termed partial birth abortion)188 · two-stage procedures involving two general anaesthetics (in which the membranes are ruptured and the umbilical cord divided, followed, some days later, by D&E) · medical abortion using instillation of various agents. There are scant published data on the safety of these methods and, to our knowledge, intact D&X has never been used in the UK. These mid-trimester abortion methods are not recommended for UK practice.

Cervical priming for surgical abortion RECOMMENDATION 36

B Cervical preparation is beneficial prior to surgical abortion and should be routine if the woman is aged under 18 years of age or at a gestation of more than 10 weeks.

RECOMMENDATION 37

C Abortion regimens containing misoprostol are not licensed within manufacturers' summaries of product characteristics. European Community regulations permit doctors to prescribe unlicensed regimens and permit pharmacists to dispense and nurses to administer medicines prescribed outside of a product licence. Women should be informed if a prescribed treatment is unlicensed.

RECOMMENDATION 38

B Based on available evidence, the following regimen appears to be optimal for cervical preparation prior to first- or second-trimester surgical abortion. This advice is based on

50

Abortion procedures

considerations of efficacy, adverse-effect profile and cost: · * misoprostol 400 micrograms (2 x 200-microgram tablets) administered vaginally, either by the woman or a clinician, 3 hours prior to surgery. The following regimens are licensed within manufacturers' summaries of product characteristics and are also appropriate for cervical preparation prior to first- or secondtrimester surgical abortion: B · gemeprost 1 mg vaginally, 3 hours prior to surgery189 · mifepristone 600 mg orally 36­48 hours prior to surgery.190

Evidence supporting recommendations 36­38

For surgical abortion, it is well established that young age is a risk factor for cervical damage86 and that increasing gestation (particularly among multiparae) is associated with increasing risk of uterine perforation.43 Use of a cervical priming technique reduces the risks of both these complications;86,43 it is therefore recommended, at least among these high-risk groups. The studies cited above relate to the use of mechanical priming agents (laminaria) that are favoured in the USA. There is less direct evidence to support the efficacy of the pharmacological priming favoured in the UK. However, one large multicentre randomised trial191 demonstrated that routine cervical priming with a prostaglandin significantly reduced the risk of short-term complications of first-trimester suction termination. Evidence table 10 summarises studies comparing various methods of cervical priming which were reviewed by the Guideline Development Group. More recent studies are summarised in Evidence table 11. The previous edition of this guideline recommended misoprostol, 400 micrograms, administered vaginally, 3 hours prior to abortion as the most cost-effective priming regimen. This recommendation was based principally on the trial of Singh et al.192 The balance of published evidence to date still suggests that this misoprostol regimen is cost effective and associated with a low incidence of adverse effects. Trials have shown that it is feasible for women to self-administer the vaginal tablets without loss of efficacy. Further studies have suggested that the sublingual route of administration results in a rapid onset of action. However, this route may be associated with increased adverse gastrointestinal effects. The use of other agents, such as nitric oxide donors and danazol for cervical priming, is the subject of current research but cannot yet be recommended in routine practice. The World Health Organization's Technical and Policy Guidance on Safe Abortion recommends "cervical preparation before surgical abortion for durations of pregnancy over 9 weeks for nulliparous women, for women younger than 18 years old, and for all women with durations of pregnancy over 12 weeks".10 This recommendation differs slightly from our own but is based on interpretation of similar data by a different group of experts. The use of misoprostol tablets for abortion procedures by the vaginal route constitutes an unlicensed indication and an unlicensed route of administration. However, the EC Pharmaceutical Directive 65/65/EEC specifically permits doctors to use "licensed medicines for indications or in doses or by routes of administration outside the recommendations given in the licence".193 This is endorsed in articles in Drug and Therapeutics Bulletin194 and Prescribers' Journal.195 The latter article emphasises that patients should be properly informed before a drug is prescribed for an unlicensed indication. Clearly, this would be of particular importance if there is even a small risk of continuing

* This regimen is unlicensed.

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The Care of Women Requesting Induced Abortion

pregnancy. Drugs prescribed by doctors outside the license can be dispensed by pharmacists and administered by nurses and midwives. In developing this guideline update, specific advice was sought from the Nursing and Midwifery Council on this point. The response from their Professional Advisory Service emphasised the necessity for signed local protocols or individual prescriptions in respect of any substance prescribed outside the terms of its product licence. It confirmed that, provided a medical practitioner has prepared and signed a local protocol or individual prescription, midwives, health visitors or nurses should comply with the request to administer the agent.

7.2 Medical methods of abortion

Early medical abortion (gestations up to 9 weeks) RECOMMENDATION 39

B Medical abortion using mifepristone plus prostaglandin is the most effective method of abortion at gestations of less than 7 weeks.

RECOMMENDATION 40

A Medical abortion using mifepristone plus prostaglandin continues to be an appropriate method for women in the 7­9 week gestation band.

RECOMMENDATION 41

A * For early medical abortion a dose of 200 mg of mifepristone in combination with a prostaglandin is appropriate.

RECOMMENDATION 42

A * Misoprostol (a prostaglandin E1 analogue) is a cost-effective alternative for all abortion procedures for which the E1 analogue gemeprost is conventionally used (that is, early medical abortion, cervical priming, mid-trimester medical abortion).

RECOMMENDATION 43

B Based on available evidence, the following regimen appears to be optimal for early medical abortion up to 9 weeks (63 days) of gestation. This advice is based on considerations of efficacy, adverse-effect profile and cost: · * mifepristone 200 mg orally followed 1­3 days later by misoprostol 800 micrograms vaginally. The misoprostol may be administered by a clinician or self-administered by the woman. For women at 49­63 days of gestation, if abortion has not occurred 4 hours after administration of misoprostol, a second dose of misoprostol 400 micrograms may be administered vaginally or orally (depending upon preference and amount of bleeding).

* This regimen is unlicensed.

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Abortion procedures

The following regimen is licensed within manufacturer's summary of product characteristics and is also appropriate for early medical abortion up to 9 weeks (63 days) of gestation: B · mifepristone 600 mg orally followed 36­48 hours later by gemeprost 1 mg vaginally.190

Evidence supporting recommendations 39­43

The Guideline Development Group summarised existing systematic reviews of the studies that resulted in the combined mifepristone plus prostaglandin regimens which are in current UK use for early medical abortion. Single agent regimens have been reviewed and found to have unacceptable failure rates. Bygdeman reviewed a number of single agents and recommended that they be abandoned in favour of combination therapies.196 In 2002, Jain et al. published the findings of a randomised trial directly comparing regimens of vaginal misoprostol alone and of mifepristone plus vaginal misoprostol in women up to 56 days of gestation.197 Complete abortion rates were 88% and 96%, respectively (P < 0.05). Single agent regimens are not considered to have a role in UK practice, where mifepristone is readily available, and are not considered further in this guideline. The literature search for the previous edition of this guideline identified no randomised controlled trials of methotrexate plus prostaglandin compared with mifepristone plus prostaglandin. Methotrexate alone and in combination with misoprostol had been investigated by a number of groups. Grimes reviewed a number of trials looking at the role of methotrexate alone or in combination with misoprostol for induced abortion.198 He concluded that methotrexate was effective when given in combination with misoprostol. Efficacy was optimal if the misoprostol was given 7 days after the methotrexate. Comparing the results of the methotrexate plus misoprostol regimens included in Grimes' review with those of mifepristone plus misoprostol discussed below, the poorer success rates, longer treatment to abortion intervals and higher continuing pregnancy rates are significant. In 2002 findings were published from a multicentre randomised trial comparing methotrexate plus misoprostol and mifepristone plus misoprostol regimens.199 Abortions induced with mifepristone completed faster than those induced with methotrexate but the overall success rates, adverse effects and complications were similar. Acceptance rates were slightly higher with mifepristone than methotrexate. In this study, the methotrexate regimen included an `optimal' dose of misoprostol (800 micrograms vaginally) whereas the mifepristone regimen included a `suboptimal' dose (400 micrograms orally). It would be expected that the advantage of the mifepristone regimen would have been more pronounced had comparable doses of misoprostol been used. Although methotrexate regimens may have a place in those countries where mifepristone is unavailable, they are not considered further in this guideline as it focuses on abortion care in the UK. Recommendation 39 is based on a systematic review of cohort studies of combined mifepristone plus prostaglandin regimens for early medical abortion, which concluded that the complete abortion rate falls as gestation advances.200 Thus, unlike the situation with conventional suction termination, medical abortion is at its most effective at the earliest stages of pregnancy (level IIb evidence). Evidence reviewed for the previous edition of this guideline indicated that medical and surgical abortion had similar efficacy and acceptability in the early first trimester. This evidence provided the basis for the recommendation that, wherever possible, women should be offered a choice of methods. Two authoritative reviews comparing options for early abortion have since been published.92,201 A Cochrane review included only five trials, some involving single-agent medical regimens.201 The reviewers concluded that more trials were needed to address efficacy and women's

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The Care of Women Requesting Induced Abortion

preferences. A comparative review by Bygdeman and Danielsson concluded: "Both methods are equally well accepted provided the woman is allowed to choose. It is not possible to state which method is best. Medical termination of early pregnancy will not replace, but is an alternative to, vacuum aspiration and ideally both methods should be available to give the woman a choice".92 The manufacturer's summary of product characteristics for mifepristone recommends a dose of 600 mg prior to prostaglandin administration for early medical abortion.190 However, evidence from a randomised trial (level Ib evidence) indicates that a dose of 200 mg has similar efficacy when compared with 400 mg or 600 mg.202 Level III evidence from large case series has confirmed that complete abortion rates as high as any described using the manufacturer's recommended regimen are achievable with a 200 mg mifepristone regimen.83,84 The WHO multicentre trial cited in the previous edition of this guideline used gemeprost as the prostaglandin.202 The WHO has since conducted a similar trial using misoprostol involving 1589 women in 17 centres internationally.203 At gestations up to 35 days, doses of 200 mg and 600 mg of mifepristone in combination with misoprostol 400 micrograms orally were compared. Both regimens had similar efficacy. The earlier WHO multicentre trial included women at gestations up to 56 days.202 The WHO has since conducted a similar trial involving 896 women at gestations of 57­63 days in ten centres internationally.204 Doses of 200 mg and 600 mg of mifepristone in combination with gemeprost 1 mg vaginally were compared. Again, both regimens had similar efficacy. The WHO has also conducted a further multicentre trial (1224 women at gestations of less than 57 days in 13 centres internationally) to investigate the effects of further reducing the dose of mifepristone.205 Four regimens were compared: · · · · mifepristone mifepristone mifepristone mifepristone 50 mg + gemeprost 0.5 mg 50 mg + gemeprost 1 mg 200 mg + gemeprost 0.5 mg 200 mg + gemeprost 1 mg.

The success rate was significantly related to the dose of mifepristone but not to the dose of gemeprost. Women receiving only 50 mg of mifepristone had a failure rate 1.6 times higher than women receiving 200 mg. A single centre trial (80 subjects) has evaluated a dose of 100 mg mifepristone in combination with misoprostol doses of 400 micrograms orally or 800 micrograms vaginally.206 The regimen including 800 micrograms vaginal misoprostol was significantly more effective than the oral regimen. In this study, the vaginal regimen achieved a complete abortion rate of 100%, suggesting that a dose of 100 mg mifepristone may be adequate. Verification from studies in other centres is required before this dose is adopted in routine practice. The conventional PGE1 analogue used for abortion procedures is gemeprost. A 1-mg pessary (used for early medical abortion, cervical priming and for each dose in mid-trimester abortion) costs approximately £20. A series of studies reviewed by the Guideline Development Group demonstrated that the alternative E1 analogue, misoprostol, which costs around £1 per dose, is also effective in all three contexts.207­213 Moreover, misoprostol is more effective if administered vaginally rather than orally.198,207,213 Data available in 2000, relating to the use of vaginal misoprostol for early medical abortion indicated that, at gestations up to 7 weeks, misoprostol is as effective as gemeprost.88 However, at gestations of 7­9 weeks, the continuing pregnancy rate may be higher when misoprostol is used.210

54

Abortion procedures

The Guideline Development Group advised that clinicians opting to substitute misoprostol for early medical abortion in the interests of economy might prefer to use gemeprost in the 7­9 week gestation band. A subsequent large case series89 has shown that using mifepristone in combination with two doses, rather than a single dose, of misoprostol abolishes this gestation effect. Evidence table 12 summarises studies relating to regimens for early medical abortion published since 1999. Together with the older studies reviewed by the Guideline Development Group in Evidence table 13, these form the basis for the regimens recommended above.

Medical abortion in the late first trimester (9­13 weeks) RECOMMENDATION 44

A Medical abortion using the following regimen is a safe, effective and acceptable alternative to surgical abortion for women between 9 and 13 weeks of gestation: · * mifepristone 200 mg orally followed 36­48 hours later by misoprostol 800 micrograms vaginally. A maximum of four further doses of misoprostol 400 micrograms may be administered at 3-hourly intervals, vaginally or orally (depending on amount of bleeding).

Evidence supporting recommendation 44

Gouk et al. described a case series of 253 women at 63­83 days of gestation.214 Women were managed using a regimen comprising mifepristone 200 mg followed 36­48 hours later by a single dose of misoprostol 800 micrograms vaginally. The complete abortion rate was 94.5%, rising to 95.7% after repeat misoprostol administration in three women. Ashok et al. described a randomised trial involving 368 women at 9­13 weeks of gestation.215 Subjects were randomly allocated to surgical abortion by vacuum aspiration under general anaesthesia or medical abortion with mifepristone 200 mg followed 36­48 hours later by up to three doses of misoprostol. The first dose comprised 800 micrograms vaginally. If abortion did not ensue, a maximum of two further doses (400 micrograms) of misoprostol were given at 3-hourly intervals either orally or vaginally depending on vaginal bleeding. The complete abortion rates (women not requiring a second procedure) were 94.6% in the medical group and 97.9% in the surgical group (difference not significant). Adverse effects were higher in the medical group but 70% indicated that they would opt for the same method in the future. The same group has subsequently reported a consecutive series of 483 women at 64­91 days of gestation managed using this regimen.216 In a routine clinical service in the UK, 54% of women in this gestation band opted for medical abortion. The complete abortion rate was 94.8% and was gestation-related. In this series, up to five doses of misoprostol were permitted, the mean number of doses being 2.3. Vyjayanthi and Piskorowsky have reported a small case series (25 women) at 9­12 weeks of gestation, managed using mifepristone 200 mg followed by gemeprost 1 mg to a maximum of five doses.217 The complete abortion rate was 96% and all but one of the women were managed as day cases.

* This regimen is unlicensed.

55

The Care of Women Requesting Induced Abortion Mid-trimester medical abortion RECOMMENDATION 45

B For mid-trimester abortion (13­24 weeks of gestation) medical abortion with mifepristone followed by prostaglandin is an appropriate method and has been shown to be safe and effective.

RECOMMENDATION 46

A For mid-trimester medical abortion, a dose of *200 mg of mifepristone is adequate.

RECOMMENDATION 47

B Surgical evacuation of the uterus is not required routinely following mid-trimester medical abortion. It should only be undertaken if there is clinical evidence that the abortion is incomplete.

RECOMMENDATION 48

A Based on available evidence, the following regimen appears to be optimal for mid-trimester medical abortion. This advice is based on considerations of efficacy, adverse-effect profile and cost: * Mifepristone 200 mg orally, followed 36­48 hours later by misoprostol 800 micrograms vaginally, then misoprostol 400 micrograms orally, 3-hourly, to a maximum of four oral doses. The following regimen is licensed within manufacturer's summary of product characteristics and is also appropriate for mid-trimester medical abortion: Mifepristone 600 mg orally, followed 36­48 hours later by gemeprost 1 mg vaginally every 3 hours to a maximum of five pessaries.190

Evidence supporting recommendations 45­48

Second-trimester medical abortion with mifepristone followed by a prostaglandin is effective and is associated with considerably shorter induction to abortion intervals than methods using prostaglandin alone or supplemented by oxytocin infusion.218­220 As discussed above, the dose of mifepristone recommended for first-trimester medical abortion is 200 mg.202 Likewise, evidence from a randomised trial resulted in a similar recommendation for the dose of mifepristone in second-trimester abortions.221 In a series of 500 cases of mid-trimester medical abortion63 only 9.4% of cases needed surgical evacuation following medical abortion. In a similar series of 956 women, the rate was 11.5%.274 The recommended regimens are based on evidence reviewed by the Guideline Development Group and summarised in Evidence table 14.

* This regimen is unlicensed.

56

Abortion procedures

Three studies published since 1999 relating to combined mifepristone and prostaglandin midtrimester regimens have been identified. Ngai et al. reported a randomised trial of 142 women at 14­20 weeks of gestation, comparing vaginal (200 micrograms, 3-hourly) and oral (400 micrograms, 3-hourly) misoprostol after mifepristone 200 mg.223 The efficacy of the two regimens was similar (complete abortion rate: 81% oral versus 75% vaginal). Although adverse effects were significantly higher in the oral group, this route was preferred by women. Tang et al. reported on a case series of 956 women at 12­24 weeks of gestation managed using a regimen comprising mifepristone 200 mg followed by gemeprost 1 mg vaginally 6-hourly for 24 hours, followed by gemeprost 1 mg 3-hourly for 12 hours, if required.222 Overall, 96.4% and 98.8% aborted within 24 and 36 hours, respectively. This combination was found to be safe and effective. Bartley and Baird reported on a randomised trial of 100 women at 12­20 weeks of gestation, comparing gemeprost and misoprostol regimens.224 All subjects received mifepristone 200 mg; the gemeprost group then received 1 mg vaginally every 6 hours for 18 hours; the misoprostol group then received one dose of 800 micrograms vaginally followed by 400 micrograms orally 3-hourly for 12 hours. Complete abortion rates, induction to abortion intervals, surgical evacuation rates and adverse-effect profiles were similar in the two groups.

7.3 Analgesia for abortion care

RECOMMENDATION 49

B Some women will require analgesia after surgical abortion or during and after medical abortion. Requirements for analgesia vary and there is no benefit in routine administration of prophylactic analgesics. Services should make available a range of oral and parenteral analgesics in order to meet women's needs.

Evidence supporting recommendation 49

In routine clinical practice, analgesia is offered to women following surgical abortion and both during and after medical abortion. There is little research evidence to guide the choice of analgesic regimens. In a large case series of early medical abortion, data on analgesic use were available for over 3000 women.89 Of these, 37% required no analgesia, 58% received oral analgesia only (paracetamol 500 mg plus dihydrocodeine 10 mg) and 5% received parenteral opiate (morphine 10 mg). Data on analgesic use63 were reported for 178 women undergoing mid-trimester medical abortion in the same centre. Of these, 26% required no analgesia, 36% received oral analgesia and 38% parenteral opiate (regimens as above). A case series of 2747 women from the USA includes data on analgesic use in a home abortion setting;225 79% of women used an oral narcotic analgesic on the day of misoprostol administration. This level of use was higher than the 27% reported by the same investigators in a series of 2121 women undergoing supervised medical abortion.226 A placebo-controlled, randomised trial evaluated the efficacy of ibuprofen or acetaminophen with codeine in the context of early medical abortion with methotrexate and misoprostol.227 The agents were taken at the time of misoprostol administration, prior to the onset of pain. Severe pain scores were reported by almost one-quarter of women. There were no significant differences in pain scores

57

The Care of Women Requesting Induced Abortion

between treatment groups. The authors concluded that pain experienced in medical abortion causes significant distress and more research is needed to reduce it. A further randomised trial evaluated prophylactic analgesia with rectal paracetamol and codeine prior to suction abortion under general anaesthesia.228 Women experienced relatively little postabortion pain and there were no significant differences between treatment groups. The authors concluded that preoperative prophylactic analgesia is unnecessary in this group of women. A similar trial evaluated the efficacy of paracetamol given rectally at the end of suction abortion under general anaesthesia.229 Again, it was concluded that routine prophylactic analgesia was not justified. A randomised trial published in 2003 evaluated the use of a nonsteroidal anti-inflammatory drug (NSAID), diclofenac, at the time of cervical priming with oral misoprostol prior to suction termination under sedation with sublingual lorazepam.230 Again, the authors concluded that the routine use of the analgesic resulted in no significant pain reduction. This study provided reassurance that cotreatment with a NSAID did not reduce the efficacy of misoprostol cervical priming (NSAIDs inhibit the production of endogenous prostaglandins and concerns have been expressed that they might attenuate the effects of exogenous prostaglandins). A randomised trial evaluated aromatherapy to reduce anxiety before abortion and found no benefit.231

7.4 Histopathology

RECOMMENDATION 50

B Routine histopathological examination of tissue obtained at abortion procedures is unnecessary.

Evidence supporting recommendation 50

Three prospective cohort studies have examined the usefulness of routine histopathological examination of tissue obtained at abortion.232­234 The first study232 included both induced (990) and spontaneous (475) pregnancy losses. The investigators found that the histological result was sometimes inconsistent with the clinical diagnosis and resulted in unnecessary investigation and treatment. They concluded that there was no obvious benefit from routine histological examination. The second study included 676 women undergoing surgical abortion at very early gestations (less than 6 weeks).233 These investigators found that surgeons' tissue inspection poorly predicted abnormal outcomes but that pathologists' examinations performed even less well. Again, the conclusion was that routine pathology examination confers no clinical benefit. The third study involved review of histological findings from 1000 consecutive induced abortions at 7­13 weeks of gestation.234 Pathological findings were reported in 5.6% of cases. These included one diagnosis of fetal polycystic kidney disease. The authors argued that this information enabled the woman to undergo prenatal diagnosis in future pregnancies. On this basis, they argued a case for routine histological examination of abortion material. However, in reality, none of the pathologies reported influenced the immediate care of the woman. In 2002, the Royal College of Pathologists published guidance on histopathology of limited or no clinical value.235 This document advised that for `social' termination of pregnancy, specimens should not be sent to the laboratory if fetal parts are visible.

58

Chapter 8

Aftercare

8.1 Rhesus prophylaxis

RECOMMENDATION 51

B Anti-D IgG (250 iu before 20 weeks of gestation and 500 iu thereafter) should be given, by injection into the deltoid muscle, to all nonsensitised RhD negative women within 72 hours following abortion, whether by surgical or medical methods.

Evidence supporting recommendation 51

The previous version of this guideline endorsed a 1999 recommendation from the Guidelines and Audit Committee of the RCOG that RhD negative women should be given anti-D IgG immunoprophylaxis following abortion.236 The recommended dose is 250 iu before 20 weeks of gestation and 500 iu thereafter. A 500-iu dose gives protection for fetomaternal haemorrhage of up to 4 ml. It is recommended that a test for the size of fetomaternal haemorrhage should be performed in the case of procedures undertaken after 20 weeks of gestation. This may be the traditional Kleihauer acid elution test or the more accurate flow cytometry, where available. If the test indicates a fetomaternal haemorrhage of greater than 4 ml, an additional 125 iu/ml of red cells should be administered.236 This RCOG guideline was updated in 2002, but the recommendations relating to anti-D after induced abortion were unchanged.237 The guideline specifically states that anti-D should be injected into the deltoid muscle, as injections into the gluteal region often reach only the subcutaneous tissues and absorption may be delayed. A structured review appraised ten published studies relating to the necessity for anti-D prophylaxis for early first-trimester abortion.238 This review concluded that, although evidence to support the use of prophylaxis in the first trimester is sparse, there is theoretical evidence of its necessity. Studies indicate that fetomaternal haemorrhage in the first trimester is of sufficient volume potentially to cause immunosensitisation. It should be noted that it is fruitless to administer anti-D IgG to RhD negative women who, on antibody screening, are found to be sensitised already. Anti-D should not therefore be administered to such women, as it is wasteful of anti-D and unnecessarily exposes women to any risks inherent in human blood products. Inadvertent administration of prophylactic anti-D IgG to an already sensitised woman, however, would not of itself cause any harm to her.

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The Care of Women Requesting Induced Abortion

8.2 Post-abortion information and followup

RECOMMENDATION 52

Following abortion, women must be given a written account of the symptoms they may experience and a list of those that would make an urgent medical consultation necessary. They should be given a 24-hour telephone helpline number to use if they feel worried about pain, bleeding or high temperature. Urgent clinical assessment and emergency gynaecology admission must be available when necessary.

RECOMMENDATION 53

C Each woman should be offered, or advised to obtain, a follow-up appointment (either within the abortion service or with the referring clinician) within 2 weeks of abortion.

RECOMMENDATION 54

On discharge, each woman should be given a letter that gives sufficient information about the procedure to allow another practitioner elsewhere to deal with any complications.

RECOMMENDATION 55

C Referral for further counselling should be available for the small minority of women who experience long-term post-abortion distress. Risk factors are ambivalence before the abortion, lack of a supportive partner, a psychiatric history or membership of a cultural group that considers abortion to be wrong.

Evidence supporting recommendations 52­55

A follow-up appointment within 2 weeks of the procedure is a requirement of early medical abortion (although it becomes optional if complete abortion is confirmed on the day of the procedure). The Birth Control Trust has advocated early follow-up as a routine for all women following abortion.239 The first 2 weeks is when immediate complications of abortion will present and when any problems with contraception should be resolved. The recent fpa publication, Early Abortions, includes similar recommendations on aftercare.50

8.3 Contraception following abortion

RECOMMENDATION 56

B Before she is discharged following abortion, future contraception should have been discussed with each woman and contraceptive supplies should have been offered if required. The chosen method of contraception should be initiated immediately following abortion.

RECOMMENDATION 57

B Intrauterine contraception can be inserted immediately following a first- or second-trimester termination of pregnancy.

60

After care RECOMMENDATION 58

B Sterilisation can be safely performed at the time of induced abortion. However, combined procedures are associated with higher rates of failure and of regret on the part of the woman.

Evidence supporting recommendations 56­58

The initiation of contraception immediately following induced abortion has advantages. The woman is known not to be pregnant, her motivation for effective contraception is high and she is already accessing health care. In addition, it has been shown that ovulation occurs within a month of first-trimester abortion in over 90% of women.240 Hormonal contraception The World Health Organization's Medical Eligibility Criteria for Contraceptive Use (WHOMEC) provides evidence-based recommendations on eligibility for contraceptive use.241 The combined oral contraceptive pill is the most common method of contraception by women aged 16­49 years, with 18% of those using any form of contraception choosing this method.242 WHOMEC recommends that benefits of the combined oral contraceptive pill immediately following first- or second-trimester termination of pregnancy outweigh any risks. Similarly, progestogen-only contraceptive pills, implants and injectables can be started immediately following termination of pregnancy. Ideally, these methods should be commenced at the time of termination, when contraceptive protection is immediate. If started after this time, additional barrier contraception is required for 7 days (combined) or for 2 days (progestogen-only).243 Two randomised trials have assessed the effects of combined oral contraception commenced immediately after early medical abortion.244,245 Both studies concluded that it is safe to offer combined oral contraception immediately after medical abortion, as it does not affect duration or amount of vaginal bleeding or the complete abortion rate. Intrauterine contraception Systematic reviews that included nine randomised trials and a total of 4476 woman years of data suggested that the insertion of a copper-bearing intrauterine contraceptive device (IUCD) at the time of surgical termination of pregnancy was safe and practical.246 However, these multicentre trials included IUCDs that are rarely used in current clinical practice (Lippes loop, Copper 7 and TCu 200). Expulsion rates were shown to be higher for insertions following second-trimester termination than for those following first-trimester termination. Delaying insertion following second-trimester termination was advised but no time frame was given. There was insufficient evidence available to compare the safety and efficacy of IUCDs inserted immediately after abortion versus delayed insertion. WHOMEC, however, recommends that there are benefits of intrauterine contraception immediately following first-trimester termination (unrestricted use) or second-trimester termination (benefits generally outweigh any risks).241 In one trial, no difference was found in the readmission rates for pelvic infection following termination in 229 women having an IUCD inserted at the time of first-trimester termination, compared with 594 women not having an IUCD inserted.247 No prophylactic antibiotics were used and IUCD continuation rates at 1 year were 72.8%. A small randomised trial investigated bleeding patterns associated with an IUCD or a levonorgestrel-releasing intrauterine system (LNG-IUS) inserted following termination of pregnancy or following menstruation.248 Results suggest that

61

The Care of Women Requesting Induced Abortion

bleeding patterns with IUCDs are similar whether inserted following termination or postmenstrually but the number of subjects lost to follow-up was high in both groups. Women having an LNG-IUS inserted following surgical termination described fewer bleeding problems compared with women having an LNG-IUS inserted postmenstrually. This was postulated to be due to an enhanced effect of levonorgestrel on the endometrium following removal of most of the superficial endometrium during the surgical procedure. Non-randomised comparative studies provide further evidence to support the safety, efficacy and acceptability of immediate post-abortion intrauterine contraception.249­251 There are few data specifically relating to IUCD insertion following medical termination of pregnancy. We suggest that an IUCD may be inserted immediately (within 48 hours) following firstor second-trimester medical abortion. Otherwise, insertion should be delayed until 4 weeks following medical abortion (as for postpartum insertions).241 Sterilisation The lifetime failure rate for sterilisation is approximately 1 in 200.252 The RCOG evidence-based guideline on male and female sterilisation highlighted that there is potentially a higher failure rate associated with sterilisation at the time of abortion.252 The Medico-legal Committee of the RCOG has commented: "In view of the increased failure rate of sterilisation procedures on those currently pregnant, it is questionable whether such operations should be carried out at all".253 Two cohort studies have shown that the immediate and short-term complications of sterilisation performed at the time of abortion are similar to the total morbidity associated with the two procedures when performed separately.254,255 Earlier reports, based on statutory notifications, overestimated complications, owing to most sterilisations being performed by laparotomy, as opposed to the laparoscopic techniques now favoured. Apart from the potential increased risk of failure, the possibility of feelings of regret has been voiced as a reason for performing sterilisation as an interval procedure. Regret associated with sterilisation may be hard to predict.256 In one randomised trial, where women had requested sterilisation at the time of abortion, they were randomised to a combination or interval procedure.254 Of women allocated to the `interval' group, 33% failed to attend for sterilisation, suggesting a change of mind once they had been able to distance themselves from the abortion itself. This study emphasises the need for careful counselling relating to sterilisation in association with abortion.

62

Chapter 9

Standards for audit and service accreditation

The Guideline Development Group and Update Group are committed to the concept of integrated clinical effectiveness activities. It is fundamental to this concept that guideline development is complemented by related audit activity. Abortion services at local level are encouraged to conduct regular audit of the care they provide. The recommendations within this guideline can serve as criteria for audit. Suggestions for audit of abortion services were provided within the RCOG document, Effective Procedures in Gynaecology Suitable for Audit.257 Some illustrative examples of these audit suggestions, with modifications in the light of this new guideline, are summarised below.

9.1 Organisation of services

The local primary/secondary care interface could be audited by assessing whether decision-toappointment intervals fall within guideline targets. The case notes of women undergoing abortion could be assessed to determine the percentage performed as day cases.

9.2 Information for women

Local services could audit the extent to which they provide accurate and unbiased information regarding induced abortion, especially with regard to potential sequelae. This could be assessed using a patient survey.

9.3 Pre-abortion management

Where neither antibiotic prophylaxis is given nor screening for sexually transmitted infections performed, the reasons should have been documented in the case notes. Case notes of women undergoing abortion could be scrutinised to determine the percentage in which antibiotic prophylaxis was given or screening for lower genital tract infection performed and positive results acted upon.

9.4 Abortion procedures

Case note review could be conducted to see which prostaglandin E1 analogue is being used for abortion procedures.

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The Care of Women Requesting Induced Abortion

The doses of mifepristone used for early and mid-trimester abortion could be audited in a case note review against the 200-mg standard. Women undergoing surgical abortion could have their case notes reviewed to determine the percentage prescribed cervical ripening agents. The percentage of women in the high-risk group (18 years or gestation under 10 weeks) prescribed cervical priming agents could be audited. The percentage of women offered and accepting local anaesthesia could be reviewed.

9.5 Aftercare

All Rh negative women undergoing induced abortion could have their case notes examined to determine the percentage who did not receive anti-D immunoglobulin or who received it but at an inappropriate dose.

64

Appendix: Evidence tables

Evidence table 1. Studies relating to the relative safety of abortion at increasing gestations

Authors Grimes et al. Ref. 43 Size of study 67 175 Study type Multicentre, prospective, observational cohort study (up to 13 weeks and later) Multicentre, prospective cohort study, observational with controls (up to 17 weeks) Outcome RR 1.4 (95% CI 1.2­1.7) associated with each 2-week increment in gestation Compared with abortion at < 9 weeks: · operations at 9­12 weeks had 5-x risk of haemorrhage · operations at > 12 weeks had 7-x risk of haemorrhage Increasing gestation was a factor in increasing the overall morbidity rate but did not reach statistical significance Fewer complications in later gestation group (P = 0.056): 5.1% < 15 weeks 2.9% 15­20 weeks Increased risk of serious complications if > 12 weeks; below 13 weeks, nonsignificant increase with gestation; after 12 weeks, RR for each 2-week increment in gestation 1.42 (95% CI 1.30­1.55) Increased risk of febrile morbidity at > 12 weeks: RR 1.43 (95% CI 1.21­1.69); RR for transfusion 2.00 (95% CI 1.10­3.64) for each 2-week gestation increment at < 12 weeks; RR for transfusion 1.48 (95% CI 1.33­1.65) for each 2-week gestation increment at > 12 weeks Complications at: 9 weeks: 1 9­12 weeks: 1.3 (95% CI 1.02­1.63) 17­20 weeks 3.3 (95% CI 2.23­5.00) Change of referral system in November 1988 Analysed notes for first half of 1989; only referrals from family planning service were compared in the before and after study (88 before and 71 after) Outcome of change in referral system: · reduction in wait to be assessed from 11 to 5 days · increase in proportion of abortions performed at early gestations (from 40% to 60% at 9 weeks and from 21% to under 10% at 12 weeks)

RCGP/RCOG

44

6105

Jacot et al.

46

3772

Buchler et al.

45

82 030

Retrospective cohort study; single centre (compared < 15 weeks with 15­20 weeks) Multicentre, prospective, observational cohort study (up to 24 weeks)

Ferris et al.

42

83 469

Retrospective database cohort study, multi-centre; abortions at all gestations

Glasier and Thong

47

1988: 2204; 1989: 2210

Surgical abortions up to 20 weeks; before-and-after study

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The Care of Women Requesting Induced Abortion

Evidence table 2. Studies relating to the rate of uterine perforation during termination of pregnancy

Authors Andolsek et al. Lindell et al. Hakim-Elahi et al. Kaali et al. Ref. 258 259 260 139 Size of study 3004 in Ljublijana 1466 in Singapore 84 850 170,000 (a) 6408 (b) 706 b = at time of laparoscopic sterilisation Gestation 7­12 weeks < 18 weeks First trimester First trimester Perforation rate 1.3 in 1000 in Ljublijana 1.4 in 1000 in Singapore 145 (1.7 in 1000) 16 (0.09 in 1000) Before direct visualisation: (a) 8 (1.3 in 1000) (b) 2 (2.8 in 1000) Unsuspected perforations: 12 (15.6 in 1000) True incidence in the laparoscopic group was 14 (2 + 12) in 706 or 19.8 in 1000 10 (0.4 in 1000) 12 (0.3 in 1000) 22 (0.4 in 1000) 22 (3.6 in 1000) Women treated in private sector had one-third the risk of trauma compared with NHS 0.9 in 1000 9 perforations ? all first trimester if so 1.1 in 1000 perforation rate 10 (1.1 in 1000) 36 (1.4 in 1000) 18 (1.2 in 1000) 13 (0.4 in 1000)

Heisterberg et al.

262

5851

RCGP/RCOG

44

6105

9 weeks 10­12 weeks All gestations 9­12 weeks

Grimes et al. King

286 263

67 175 11 885

Up to 24 weeks (86% < 13 weeks) 8238 in first trimester 3647 in second < 14 weeks First trimester Up to 12 weeks

Hodgson et al. Nathanson et al. Beric et al.

264 265 266

104 453 26 000 14 261 by curettage 22 905 by vacuum aspiration

Evidence table 3. A summary of the incidence of cervical injury during first-trimester abortion by vacuum aspiration reported in illustrative large case series

Study Andolsek et al. Ferris et al. RCGP/RCOG Jacot et al. Hakim-Elahi et al. Heisterberg et al. Schulz et al. Ref. 258 42 44 46 260 262 86 Gestation 7­12 weeks 87% < 13 weeks 88% < 13 weeks 5­14 weeks Up to 14 weeks First trimester 12 weeks Abortions (n) 6655 83 460 6105 3225 170 000 5851 15 438 Cervical injury 4 63 11 1 18 5 159 Rate/1000 0.6 0.7 1.8 0.3 0.1 0.8 10.3

Evidence table 4. A summary of the incidence of cervical injury during second-trimester abortion by dilatation and evacuation in illustrative large case series

Authors Jacot et al. Schulz et al. Peterson et al. Ref. 46 86 267 Gestation 15­26 weeks 13­20 weeks 14­16 weeks Abortions (n) 547 6213 9916 Cervical injury 0 72 109 Rate/1000 11.6 11.6

66

Evidence tables

Evidence table 5. Studies relating to induced abortion and subsequent breast cancer risk

Authors Thorp et al. Tavani et al. Marcus et al. Fioretti et al. Newcomb and Mandelson Lasovich et al. Tang et al. Robertsona et al. Sanderson et al. Goldacre et al. Ye et al. Mahue-Giangreco et al. Becher et al. Erlandsson et al. Paoletti et al. Year 2002 1999 1999 1999 2000 2000 2000 2001 2001 2001 2002 2003 2003 2003 2003 Ref. 75 268 269 270 271 112 111 272 109 110 273 274 275 276 277 Study design Narrative review Case­control Case­control Case­control Case­control Cohort Case­control Case­control Case­control Case­control Cohort and case­control Case­control Case­control Case­control Cohort Subjects (n) Conclusions

Cannot exclude a significant association; OR 1.3 (95% CI 1.2­1.4) 579 cases Abortion was not related to risk of breast cancer at age 668 controls < 40 years; OR 0.87 (95% CI 0.63­1.22) 862 cases Abortion during adolescence does not influence breast 790 controls cancer risk; RR 1.2 (95% CI 0.6­2.7) 1041 cases Abortion was not related to breast cancer risk in 1002 controls nulliparous women; OR 0.97 (95% CI 0.64­1.47) 138 cases Abortion was not related to risk of breast cancer; RR 0.9 252 controls (95% CI 0.5­1.6) 37 247 No excess risk of breast cancer among women who reported having an abortion; RR 1.1 (95% CI 0.8­1.6) 463 cases Abortion does not increase risk of breast cancer; RR 0.9 2201 controls (95% CI 0.7­1.2) 624 cases Abortion was not associated with a statistically 624 controls significant elevated risk in any parity group 1459 cases There was no relation between abortion and breast 1556 controls cancer; OR 0.9 (95% CI 0.7­1.2) 28 616 cases Abortion does not increase the risk of breast cancer; OR 325 456 controls 0.83 (95% CI 0.74­0.93) 267 040 (cohort) 694 controls Abortions are not an important cause of 652 cases breast cancer; RR 0.51 (95% CI 0.31­1.50) 744 cases Does not support the hypothesis that abortion increases 744 controls breast cancer risk; OR 0.71 (95% CI 0.49­1.02) 706 cases A history of abortion showed no significant effect 1633 controls 1759 cases Abortion is not associated with an increased risk of 1759 controls breast cancer; OR 0.80 (95% CI 0.64­1.00) 92 767 There is no relationship between breast cancer and induced abortion; RR 0.91 (95% CI 0.82­0.99)

Note: as this guideline was going to press, a major systematic review114 was published which lent further support to these conclusions

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The Care of Women Requesting Induced Abortion

Evidence table 6. Studies relating to future reproductive outcomes

Authors Infertility Daling et al. Ref. 115 Size of study 105 medical histories 199 control cases 127 with known diagnosis of tubal infertility 395 women who conceived a child at same time as infertile women began attempt to become pregnant 850 Type of study Retrospective case­control Population-based case­control Outcome Nonsignificant association between prior abortion and secondary infertility (RR 1.35, 95% CI 0.71­2.43) Nonsignificant association between prior abortion and secondary infertility (RR 1.15, 95% CI 0.70­1.89)

Daling et al.

116

Hernadi et al.

117

Cohort study (within multicentre trial)

Tzonou et al.

118

84 women with secondary infertility 168 pregnant controls

Case­control study

Nonsignificant association between prior abortion and secondary infertility Cumulative pregnancy rates at 30 months were 96.9 (abortion group) and 98.7% (controls) Small significant association between prior abortion and secondary infertility (RR 2.1, 95% CI 1.1­4.0)

Preterm delivery Dalaker et al. 121

619 terminations 619 pregnancies continued to delivery

Cohort

Berkowitz

119

Meirik et al. Maritius et al.

122 120

175 mothers of singleton preterm infants 313 mothers of singleton term infants 429 post-abortion 391 controls 106 345 singleton births

Case­control

Groups compared for subsequent complications such as first- and second-trimester abortion, cervical weakness, preterm delivery, ectopic pregnancy and sterility; total complication rate was 24.3 in the abortion group and 20.2 in the controls Significant risk factor for preterm delivery included induced abortion in previous pregnancy

Cohort Cross-sectional survey

No association between induced abortion and preterm delivery Association between preterm delivery and previous induced abortion (OR 1.8, 95% CI 1.57­2.13)

68

Evidence tables

Evidence table 7. Induced abortion and subsequent mental health

Authors Reardon and Cougle Gissler et al. Ref. 278 Location (epoch) USA (1984­91) Finland (1987­94) Subjects and study design 293 abortion 128 unplanned birth Longitudinal cohort 1347 suicides in women aged 15­49 years Register linkage to pregnancy events in previous year (retrospective cohort) 143 attempted suicides in women aged 15­49 years Register linkage to pregnancy events (retrospective cohort) 50 260 women, 1st pregnancy abortion 83 690 women, 1st pregnancy, delivery Register linkage to death certificates (cohort) Women with `unplanned' pregnancies: 6151: no abortion request 6410: obtained abortion 379: abortion refused 321: requested but changed mind (cohort) Women with pregnancies in 1989, no psychiatric admission in previous year 15 299 abortion 41 442 birth Record linkage to psychiatric admissions (cohort) Outcomes Depression (CES-D score > 15) Suicide Findings Risk of high depression score, abortion versus unplanned birth: Adj. OR 1.54 (95% CI 0.91­2.61) Suicide rates: ­ all women 15­49: 11.3 in 100 000 ­ after birth: 5.9/100,000* ­ after miscarriage: 18.1 in 100 000* ­ after abortion: 34.7 in 100 000* (* significant different from `all women') Attempted suicide rates: ­ after birth: 1.9 in 1000 ­ after miscarriage: 4.3 in 1000 ­ after abortion: 8.1 in 1000 `Deterioration in mental health may be a consequential side effect of induced abortion' Age adjusted relative risk of suicide; women with one pregnancy only; abortion versus delivery: 2.54 (95% CI 1.14­5.67)

279

Morgan et al.

280

Wales (1991­95)

Attempted suicide

Reardon et al.

281

California (1989­97)

Suicide

Gilchrist et al.

282

UK (1976­79)

Any psychiatric illness Deliberate self-harm

Total psychiatric disorders similar after abortion or delivery Deliberate self-harm more common in `abortion group': RR 1.7 (95% CI 1.1­2.6) and `abortion refused group': RR 2.9 (95% CI 1.3­6.3) First-time psychiatric admission rates during 4 years after pregnancy event Adjusted OR, abortion group versus delivery group: 1.7 (95% CI 1.4­2.1)

Reardon et al.

283

California (1989­93)

Psychiatric admissions

69

The Care of Women Requesting Induced Abortion

Evidence table 8. Studies relating to local versus general anaesthesia

Author De Jonge et al. Ref. 284 Size of study 142 Type of study Prospective randomised trial Outcome Randomised into 2 groups: ­ those for evacuation under systemic analgesia ­ those under general anaesthesia Both groups compared in terms of safety, efficacy, acceptability, blood consumption and time delay between admission and evacuation Significantly less blood use in ward group (37 units for 13 patients) than in theatre group (65 units for 24 patients (P < 0.003) Significantly less time taken between admission and evacuation in ward group (median 7 hours 15 minutes) theatre group (median 12 hours 38 minutes) (P < 0.003) Evacuation under fentanyl and midazolam was safe, effective and acceptable for majority of patients compared with evacuation users Women who had D&E under general anaesthesia had a relatively high risk of complications of 2.6 (95% CI 1.4­4.9) compared with women who underwent D&E under local anaesthesia LA for second trimester appears to be both safer and less expensive than GA Significant differences between LA and GA for specific complications LA associated with higher rates of febrile and convulsive morbidity GA higher rates of haemorrhage, cervical injury and uterine perforation

MacKay et al.

285

4147 GA 5389 LA

Randomised trial

Grimes et al.

286

36 430

Case study

D&E = dilatation and evacuation; GA = general anaesthesia; LA = local anaesthesia

Evidence table 9. Studies comparing manual with electric vacuum aspiration, randomised controlled trials

Study Edelman et al. Hemlin and Moller Bird et al. Bird et al. Dean et al. Year 2001 2001 Ref. 287 288 Participants 114 at < 77 days 200 at < 56 days Intervention(s) Electric versus manual vacuum aspiration (LA) Findings Electric suction gave shorter operating times Objective pain measures similar; noise of electric suction increased subjective pain No differences in efficacy No information on operating time or patient preference No major differences in acceptability (no information on other outcomes) Similar patient acceptability (no information on other outcomes) Operating times, blood loss, complications, similar Patient pain and satisfaction similar 19% `bothered' by noise in electric group

2001 2003 2003

289 290 291

Electric versus manual vacuum aspiration (under LA/GA according to preference) 42 at < 77 days Electric versus manual vacuum aspiration (LA) 127 at < 11 weeks Electric versus manual vacuum aspiration (under LA) 84 at < 10 weeks Electric versus manual vacuum aspiration (LA + conscious sedation)

GA = general anaesthesia; LA = local anaesthesia

70

Evidence tables

Evidence table 10. Cervical priming, randomised controlled trials (first-trimester abortion)

Author Kajanoja et al. Ref. 292 Population 239 nulliparous women undergoing vacuum aspiration first trimester TOP: 147 treatment; 146 placebo Intervention Randomised, doubleblind, placebo-controlled, 6-centre study: ­ single 1-mg gemeprost vaginal suppository for dilatation of the cervix uteri ­ placebo Suppository inserted 3 hours before vacuum aspiration Single-centre prospective randomised trial: ­ gemeprost 1-mg pessary 1­4 hours before surgery ­ PGE2 10-mg pessary Results Preoperative os diameter was significantly greater in women treated with gemeprost. Further mechanical dilatation was either unnecessary or significantly easier than in placebo-treated women. A significant reduction in operative blood loss in the gemeprost group Gemeprost pessaries produced Gemeprost 1-mg marginally greater cervical pessaries are to be dilatation and less operative preferred to PGE2 blood loss than PGE2, with pessaries a reduction in distressing preoperative adverse effects. Postoperative adverse effects and later complications were infrequent and similar for the two groups In 35% of treated women, there Mifepristone for was no need for further dilatation cervical priming is prior to evacuation of the uterus. safe and effective and All women in placebo group has advantages over required further dilatation. In prostaglandins and those women receiving hydrophilic cervical mifepristone who did require dilators further dilatation, initial dilatation of the cervix was significantly greater and significantly less force was required to dilate the cervix to 9 mm. Perioperative blood loss was reduced. No serious complications or adverse effects No abortion or vaginal bleeding occurred in any of the women. After 500 micrograms PGE2 gel, mean free passability was significantly higher than in placebo group. Prostaglandin pretreatment led to a significant increase in dilation. Adverse effects: 17 of the 25 PGE2-treated women complained of lower abdominal pain; gastrointestinal adverse effects were observed. In placebo group there were no undesired symptoms. No intra- or postoperative complications occurred in PGE2 gel-treated group No significant differences Mifepristone oral between active treatment groups route easier and in: baseline cervical dilatation; cheaper force required to dilate cervix; volume of intraoperative blood loss. Both drugs were significantly more effective than placebo. Significantly fewer women in mifepristone group had adverse effects than in gemeprost group Comments

MacKenzie et al. 293

1030 women for first-trimester aspiration TOP

Urquhart and Templeton

220

40 primigravidae at 10­13 weeks of gestation

RCT of: ­ placebo ­ 600 mg single oral dose of mifepristone 48 hours prior to vacuum aspiration under GA

Osmers et al.

294

50 primigravidae scheduled for TOP in first trimester

Placebo-controlled double-blind randomised study: ­ 500 micrograms PGE2 gel applied intracervically 6 hours before curettage ­ placebo gel applied intracervically 6 hours before curettage

Henshaw and Templeton

295

90 primigravid women for late first-trimester vacuum aspiration TOP between 9 and 13 weeks

RCT of: ­ 200 mg mifepristone orally 36 hours before operation ­ placebo ­ 1-mg gemeprost vaginal pessary 3-4 hours preoperatively

71

The Care of Women Requesting Induced Abortion

Evidence table 10. Cervical priming, randomised controlled trials (first-trimester abortion) (continued)

Author el-Refaey et al. Ref. 211 Population 90 primigravid women requesting termination between 9 and 13 weeks Intervention RCT groups of: ­ gemeprost ­ vaginal misoprostol ­ controls Results Comments Cervical predilation with misoprostol may be considered in all women having surgically induced abortions

Ngai, Tang et al.

296

Ngai, Yeung et al. 297

Ngai, Yeung et al. 298

Lawrie et al.

299

Both induced clinical and histochemical changes that were significantly different from controls and were likely to have therapeutic value. Misoprostol is cheap, easily stored and associated with few adverse effects 75 women ­ oral misoprostol In nulliparous women, median (primiparous and ­ placebo group cervical dilatation in treatment multiparous) group was significantly greater undergoing vacuum than that in placebo group aspiration between (7.8 mm versus 3.7 mm). In 6 and 12 weeks multiparous women, difference was also statistically significant (9.8 mm versus 6 mm). Ease of dilatation, assessed subjectively by the operating surgeons, was significantly improved in treatment group. Significant reduction in duration of operation and mean blood loss in treatment group. Adverse effects encountered in treatment group were mild and well accepted by the women 64 nulliparous Randomised to: Median cervical dilatation at women, 6­12 weeks ­ 400 micrograms vacuum aspiration in the of pregnancy, misoprostol orally misoprostol group was undergoing vacuum ­ 1 mg vaginal gemeprost significantly greater than that in aspiration TOP at 12 hours prior to the gemeprost group (8 mm vacuum aspiration versus 7 mm). Preoperative ­ 1 mg vaginal adverse effects were significantly gemeprost at 3 hours prior less frequent in the misoprostol to vacuum aspiration group. Ease of dilatation assessed subjectively by the operating surgeons was improved significantly in the misoprostol group. Duration of operation and blood loss were similar in both groups 100 nulliparous Prospective randomised No significant differences in: women undergoing trial. ­ baseline cervical dilatation TOP between 8 and Group 1: placebo ­ incidence of side effects 12 weeks of gestation and misoprostol ­ amount of blood loss 400 micrograms 36 and ­ duration of procedure. 12 hours respectively before vacuum aspiration Group 2: 200 mg mifepristone and placebo 36 and 12 hours respectively prior to operation 60 consecutive Randomised to: No significant differences women scheduled ­ 400 micrograms oral between oral and vaginal for daycase misoprostol, treatment groups in relation to suction TOP self-administered basal dilatation, cumulative force 12 hours before surgery to achieve 9-mm dilatation or ­ 800 micrograms gastrointestinal adverse effects. vaginally, 2­4 hours Those in oral group experienced prior to surgery more severe pain and heavier preoperative bleeding. 2 women in oral group experienced incomplete abortion at home after taking misoprostol and one other patient required early admission because of heavy bleeding

Oral misoprostol is an effective and safe method for cervical dilatation prior to vacuum aspiration in first-trimester pregnancy

Since misoprostol is also much cheaper and more convenient to use, authors conclude that oral misoprostol is better than vaginal gemeprost for cervical dilatation prior to vacuum aspiration in firsttrimester pregnancy

Misoprostol and mifepristone are of similar effectiveness for cervical priming prior to vacuum aspiration in nulliparous women

Because of unpredictability of action of oral misoprostol, with incomplete abortion or heavy bleeding occurring prior to admission in three women, authors cannot recommend the dosage schedule evaluated in this study for routine clinical use

72

Evidence tables

Evidence table 10. Cervical priming, randomised controlled trials (first-trimester abortion) (continued)

Author Fong et al. Ref. 300 Population Intervention Results Only 7 (23.3%) of 200-micrograms group achieved a dilatation of 8 mm, compared with 29 (96.7%) in 400-micrograms group. Mean cervical dilatation in 200-micrograms and 400-micrograms groups were 6.4 mm and 8.2 mm, respectively. No conferred benefit from increasing insertion to aspiration interval beyond 3 hours 29 (96.7%) women in 400-micrograms group and all in 600-micrograms and 800-micrograms groups achieved cervical dilation of at least 8 mm. Success rate for 200-micrograms group was only 23.3%, significantly less efficacious than 400-micrograms dose (OR 95.3, 95% CI 10.9­830.9) No significant difference among 400-, 600- and 800-micrograms groups with respect to achieving cervical dilation at least 8 mm. 800 micrograms was associated with significantly more adverse effects than 600 micrograms (preoperative and intraoperative blood loss, abdominal pain, products of conception at os, fever higher than 38°C). When 400 micrograms and 600 micrograms were compared, higher dose also was associated with significantly more adverse effects Comments Vaginal application of 400 micrograms misoprostol appears to be the optimum dose for preabortion cervical priming in first trimester

60 women undergoing Randomisation to: vacuum aspiration ­ 200 micrograms abortion misoprostol vaginally ­ 400 micrograms misoprostol vaginally

Singh et al.

192

121 women undergoing vacuum aspiration abortion

Randomisation to: ­ 200 micrograms misoprostol vaginally ­ 400 micrograms misoprostol vaginally ­ 600 micrograms misoprostol vaginally ­ 800 micrograms misoprostol vaginally Vacuum aspiration was performed 3­4 hours after the insertion of misoprostol tablets

Vaginal application of 400 micrograms misoprostol is optimal dose for vacuum aspiration preabortion cervical dilation in firsttrimester nulliparae

73

The Care of Women Requesting Induced Abortion

Evidence table 11. Studies relating to cervical priming prior to surgical abortion, published since 1999

Study Study type Year Ref. Subjects Interventions Findings

Misoprostol prior to MVA: placebo-controlled trials Okanlomo et al. RCT 1999 301 136 1st trimester

de Jonge et al.

RCT

2000

302

287 1st trimester

Misoprostol 600 micrograms orally x 2 versus placebo x 2, 12 and 4 hours prior to MVA Misoprostol 600 micrograms versus placebo self-administered vaginally 2­4 hours prior to MVA

At gestations > 8 weeks, priming reduced operative time and blood loss Self-administration of this regimen is feasible, safe and effective

Misoprostol: route and dose Singh et al. RCT 1999

303

60 nulliparous, 1st trimester

Singh et al.

RCT

1999

304

Henry and Haukkamaa

RCT

1999

305

Ngai et al.

RCT

1999

306

Singh et al.

RCT

1999

307

Carbonell et al.

RCT

2001

308

Todd et al.

Ret. cohort

2002

309

Tang et al.

RCT

2002

310

Saxena et al.

RCT

2003

311

Vimala et al.

RCT

2003

312

Misoprostol: 400 micrograms vaginally 3 hours prior to suction versus 600 micrograms vaginally 2 hours prior to suction 180 nulliparous, Misoprostol: 400 micrograms 1st trimester vaginally 3 hours prior to suction versus 600 micrograms vaginally 2 hours prior to suction versus 800 micrograms vaginally 2 hours prior to suction 199 1st trimester Misoprostol 200 micrograms vaginally, > 4 hours prior to suction versus gemeprost 1 mg > 3 hours prior to suction 225 nulliparous, Placebo versus misoprostol: 1st trimester oral 200 micrograms; oral 400 micrograms; vaginal 200 micrograms; vaginal 400 micrograms; 3 hours prior to suction 120 nulliparous, Misoprostol 200 micrograms in 1st trimester water, vaginally versus misoprostol 200 micrograms in acetic acid, vaginally 3­4 hours prior to suction 900 up to 63 days Misoprostol 400 micrograms orally 8 hours prior to suction versus misoprostol 400 micrograms, self-administered vaginally 4 hours prior to suction 110 at 14­18 Misoprostol 600 micrograms weeks buccally 2­4 hours prior to D&E versus laminaria tents 12 hours prior to D&E 40 1st trimester Misoprostol 400 micrograms: sublingual versus oral versus vaginal versus vaginal + water 6 hours prior to suction 100 1st trimester Misoprostol 400 micrograms sublingually 3 hours prior to suction versus no priming 60 1st trimester Misoprostol 400 micrograms sublingually versus placebo, 2 hours prior to suction

400 micrograms/3 hours regimen is more effective and has fewer adverse effects 400 micrograms/3 hours regimen is more effective and has fewer adverse effects

Similar efficacy; significantly fewer adverse effects with misoprostol Efficacy and adverse effects of 400 micrograms orally and 400 micrograms vaginally is similar

No difference in efficacy or adverse effects

Vaginal self-administration was more effective with a much lower frequency of adverse effects Similar efficacy

Serial serum levels showed the sublingual route had greatest bioavailability and earliest peak level Sublingual misoprostol was effective and acceptable compared with no priming Sublingual misoprostol was effective compared with placebo but had significant adverse effects Vaginal misoprostol most effective and acceptable of the 3 regimens Mifepristone 48 hours prior most effective. Acceptability similar

Comparisons of various priming agents MacIsaac et al. RCT 1999 313

106 1st trimester

Ashok et al.

RCT

2000

314

90 1st trimester

Misoprostol 400 micrograms orally versus misoprostol 400 micrograms vaginally versus Laminaria tent, 4 hours prior to suction Misoprostol 800 micrograms vaginally 2­4 hours prior to suction versus mifepristone 200 mg orally 24 or 48 hours prior to suction

74

Evidence tables

Evidence table 11. Studies relating to cervical priming prior to surgical abortion, published since 1999 (continued)

Study Facchinetti et al. Study type RCT Year 2000 Ref. 315 Subjects 36 nulliparous, 1st trimester Interventions Placebo versus 1% intracervical nitroprusside gel 6 hours prior to suction versus 2% nitroprusside gel 3 hours prior to suction Isosorbide mononitrate 40 mg vaginally versus misoprostol 400 micrograms vaginally versus both agents together, 3 hours prior to suction 200 mg danazol vaginally x 3 over 2 days versus placebo, both followed by misoprostol 200 micrograms vaginally 5 hours prior to suction Lamicel® tent, 1­4 hours prior to suction versus gemeprost 1 mg 2­8 hours prior to suction Misoprostol 400 micrograms, vaginally, versus gemeprost 1 mg, 3­4 hours prior to suction Findings Both regimens of nitroprusside were effective compared with placebo, with no significant adverse effects No advantage of combining isosorbide mononitrate with misoprostol

Ledingham et al.

RCT

2001

316

66 nulliparous, 1st trimester

Zalanyi

RCT

2001

317

52 nulliparous, 1st trimester

Pretreatment with danazol enhances the effect of misoprostol in a manner similar to antigestagen No information on efficacy. Complication rate higher with Lamicel Similar efficacy. No information on adverse effects

Lindelius et al.

Ret. cohort RCT

2003

318

622 1st trimester

Ekerhovd et al.

2003

319

90 nulliparous, 1st trimester

75

The Care of Women Requesting Induced Abortion

Evidence table 12. Studies relating to combined early medical abortion regimens with mifepristone (oral) and prostaglandin, published since 1999

Authors Trussell and Ellertson Schaff et al. Study type SR Year Ref. Subjects (timing) Intervention(s) Findings `Success' rates: 85­100%

1999 320

CS

1999 55

Takkar et al.

RCT

1999 321

Sandstrom et al.

RCT

1999 322

Kahn et al. Meta-anal. 2000 91

Multiple trials, including Various mifepristone­misoprostol 13 mifepristone/ regimens misoprostol 933 (up to 56 days) Mifepristone 200 mg + misoprostol 800 micrograms vaginally (self-administered at home) 101 (up to 56 days) Mifepristone 200 mg + Meteneprost® (Cayman Chemical Co., Ann Arbor, MI) 5 mg vaginally or misoprostol 600 micrograms orally 64 (up to 56 days) Mifepristone 600 mg + gemeprost 1 mg 24 hours later or gemeprost 1 mg 48 hours later 54 studies, including Various regimens 18 mifepristone/ misoprostol

Complete abortion rate: 97% Continuing pregnancy: 0.5% Acceptability: 94% Misoprostol regimen significantly more effective

No difference in efficacy or adverse effects Efficacy decreases with increasing gestation: < 49 days: success 94­96% 50­56 days: 91% 57 days: 85­95% 2 misoprostol doses improves efficacy at some gestations Complete abortion rate: 97% up to 56 days 96% at 57­63 days Continuing pregnancy: 0.44% Acceptability 91%

Schaff et al.

CS

2000 323

1137 (up to 63 days)

Aubeny and Chatellier

RCT

2000 234

237 (up to 49 days)

ICMR Task Force Bartley et al.

RCT

2000 325

893 (up to 63 days)

CS

2000 90

3161 (up to 63 days)

Mifepristone 200 mg + misoprostol 800 micrograms vaginally (self-administered at home or clinician administered, according to preference) 48 hours later. Option of 2nd dose of misoprostol at follow-up Mifepristone 600 mg + misoprostol 400 micrograms orally or vaginally. Option of 2nd dose of misoprostol at 3 hours Mifepristone 200 mg + Meteneprost® 5 mg vaginally or misoprostol 600 micrograms orally Mifepristone 200 mg + gemeprost 0.5 mg vaginally

Complete abortion rate: 98.7% No significant difference between groups Similar efficacy. More adverse effects in oral misoprostol group Complete abortion rate: 96.2% Continuing pregnancy: 1.4% Efficacy was better at lower gestations and in nulliparous women Complete abortion rate: 97.2% Continuing pregnancy: 0.7% No difference between groups, i.e. misoprostol can be given any time between 1 and 3 days after mifepristone Complete abortion rate: 98%

Schaff et al.

RCT

2000 326

2295 (up to 56 days)

Pymar et al.

CS

2001 327

40 (up to 49 days)

Bartley et al.

RCT

2001 328

999 (up to 63 days)

Xu et al.

Prosp. cohort RCT

2001 329

192; 35 with scarred uterus (up to 49 days) 86 (up to 49 days)

Creinin et al.

2001 330

Mifepristone 200 mg + misoprostol 800 micrograms vaginally (self-administered at home) 1 day versus 2 days versus 3 days later. Option of 2nd dose of misoprostol at follow-up Mifepristone 200 mg + misoprostol 800 micrograms vaginally (self-administered at home) 6­8 hours later. Option of 2nd dose of misoprostol at 48 hours Mifepristone 200 mg + misoprostol Complete abortion rate: 98.7% 800 micrograms or gemeprost (misoprostol) versus 96.2% 0.5 mg vaginally (gemeprost) "vaginal misoprostol is the preferred prostaglandin because of fewer failures particularly at > 49 days" Mifepristone 25 mg twice daily for Regimen appeared safe and 3 days + misoprostol 600 micrograms effective in women with scarred orally uterus Mifepristone 600 mg + misoprostol 6­8 hour regimen was 400 micrograms orally 6­8 hours significantly less effective later versus 48 hours later. Option of 2nd dose of misoprostol at 48 hours

76

Evidence tables

Evidence table 12. Studies relating to combined early medical abortion regimens with mifepristone (oral) and prostaglandin, published since 1999 (continued)

Authors Schaff et al. Study type RCT Year Ref. Subjects (timing) 1168 (up to 63 days) Intervention(s) Mifepristone 200 mg + misoprostol 400 micrograms orally x 2, 2 hours apart, versus misoprostol 800 micrograms vaginally (selfadministered at home) 1 day later Mifepristone 200 mg + misoprostol 800 micrograms vaginally (after varying time intervals) Mifepristone 200 mg + misoprostol 800 micrograms vaginally 6­8 hours later. Option of 2nd dose of misoprostol at 48 hours Mifepristone 200 mg + misoprostol 800 micrograms vaginally. Option of 2nd dose of misoprostol (400 micrograms) at 4 hours Findings Complete abortion rate: 90% (oral misoprostol) versus 97% (vaginal misoprostol): "vaginal misoprostol is more effective" Complete abortion rate 97.4%

2001 331

Allen et al.

CS

2001 332

4393 (up to 63 days)

Fox et al.

CS

2002 333

80 (at 50 to 63 days)

These pilot results suggest the regimen is effective

Ashok et al.

CS

2002 89

4132 (up to 63 days)

Schaff et al.

RCT

2002 334

1045 (up to 63 days)

Mifepristone 200 mg + misoprostol 400 micrograms orally (x 1 or x 2) 2 hours apart versus misoprostol 800 micrograms vaginally (selfadministered at home) 1 day later Mifepristone 200 mg + misoprostol 800 micrograms orally (with misoprostol 400 micrograms twice daily for 7 days) versus misoprostol 800 micrograms vaginally (with misoprostol 400 micrograms twice daily for 7 days) versus misoprostol 800 micrograms vaginally Mifepristone 200 mg + misoprostol 800 micrograms sublingually

Tang et al.

RCT

2002 335

150 (up to 63 days)

Complete abortion rate: 98% (incorporating the 2nd dose option into the regimen reduced the continuing pregnancy rate and eliminated the gestationeffect on overall efficacy) Complete abortion rate: 84% (400 micrograms oral misoprostol) versus 92% (800 micrograms oral misoprostol) versus 96% (vaginal misoprostol): "vaginal misoprostol is more effective" 1-week course of misoprostol did not diminish post-abortion bleeding

Tang et al.

CS

2002 336

100 (up to 63 days)

Complete abortion rate: 94%: "further trials needed to compare with vaginal route"

Routes as indicated; prostaglandin administered 48 hours after mifepristone, except where stated; CS = case series; Meta-anal. = metaanalysis; Prosp. cohort = prospective cohort; RCT = randomised controlled trial; SR = systematic review

77

The Care of Women Requesting Induced Abortion

Evidence table 13. Studies comparing various regimens used in first-trimester abortions

Authors Ref. Gestational limits Regimen Subjects Reported (n) success rate (%) P Results and conclusions

Oral misoprostol or vaginal gemeprost following mifepristone (200 mg, 400 mg or 600 mg) Sang et al. 337 < 63 days of 50 mg oral mifepristone 284 94.4 1.0 amenorrhoea followed by 4 doses 25 mg oral mifepristone at 12-hour intervals + 600 micrograms oral misoprostol 48 hours later 200 mg oral mifepristone + 141 94.6 600 micrograms oral misoprostol 48 hours later 200 mg oral mifepristone + 600 micrograms oral misoprostol 48 hours later McKinley 338 < 63 days of 200 mg oral mifepristone + et al. amenorrhoea 600 micrograms oral misoprostol 48 hours later 110 93.6 1.0 600 mg oral mifepristone + 600 micrograms oral misoprostol 48 hours later 110 93.6

Success defined as complete abortion without surgical intervention. Subjects whose outcome was undetermined were counted as failures (3 in group 1 and 1 in group 2). Maximum duration not stated. Conclusion: misoprostol in combination with mifepristone was as effective as PG05 vaginal suppository

World Health 191 7­28 days of 200 mg oral mifepristone + 1 mg Organization menstrual delay vaginal gemeprost 48 hours later 400 mg oral mifepristone + 1 mg vaginal gemeprost 48 hours later. 600 mg oral mifepristone + 1 mg vaginal gemeprost 48 hours later.

388 391 389

93.8 91.8 94.3

Success defined as complete abortion without surgical intervention. Maximum duration not stated. Conclusions: 1) recommended dose of mifepristone could be reduced from 600 mg to 200 mg without the loss of clinical efficacy 2) combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing women < 50 days of amenorrhoea 3) at gestations of > 56 days, this combination may result in too many incomplete abortions to be clinically effective 0.95 Success defined as complete abortion without surgical intervention. Subjects whose outcome was undetermined (including 6 who did not take or vomited the mifepristone tablets) were counted as failures (5 in group 1; 5 in group 2; 7 in group 3). Subjects not meeting inclusion criteria were excluded. Maximum duration not stated. Conclusion: for termination at early pregnancy a single dose of 200 mg mifepristone is as effective as currently recommended dose of 600 mg, when used in combination with vaginal pessaries of 1 mg gemeprost

Oral misoprostol versus vaginal gemeprost following mifepristone (200 mg) Baird et al. 210 < 63 days of 200 mg oral mifepristone + 0.5 mg 391 amenorrhoea vaginal gemeprost 48 hours later 200 mg oral mifepristone + 386 600 micrograms oral misoprostol 48 hours later

96.7 94.6

0.164 Success defined as complete abortion without surgical intervention. 2 women with elective surgical intervention before prostaglandin and 21 women LFU excluded. Maximum duration 12­16 days after administration of prostaglandin. Recommended dose of mifepristone and gemeprost can be reduced without impairing clinical efficacy in pregnancies < 63 days amenorrhoea

78

Evidence tables

Evidence table 13. Studies comparing various regimens used in first-trimester abortions (continued)

Authors Ref. Gestational limits Regimen Subjects Reported (n) success rate (%) 86.9 94.7 P Results and conclusions

Oral misoprostol versus vaginal misoprostol following mifepristone 600 mg oral mifepristone + 130 el-Refaey 207 < 63 days of et al. amenorrhoea 800 micrograms oral misoprostol 36­48 hours later 600 mg oral mifepristone + 133 800 micrograms vaginal misoprostol 36-48 hours later

< 0.001 Success defined as complete abortion without surgical intervention after administration of misoprostol. Maximum duration 14 days after misoprostol administration. Incidence of vomiting and diarrhoea significantly higher in oral group

79

The Care of Women Requesting Induced Abortion

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions

Authors Ref. Population Intervention Results Median interval between administration of prostaglandin and abortion was significantly shorter in mifepristone group (6.8 hours) compared with placebo group (15.8 hours). Women pretreated with mifepristone required significantly fewer gemeprost pessaries to induce abortion and experienced significantly less pain than the women who received placebo Comments

Mifepristone versus placebo Rodger and 218 100 women at Double-blind randomised Baird 12­18 weeks trial of 600 mg oral mifepristone or placebo tablets, 36 hours before the administration of gemeprost pessaries

Mifepristone: different doses and routes el-Refaey and 213 70 women at 2 different routes of Templeton 13­20 weeks administration: vaginal or a combination of vaginal and oral Pre-treated with mifepristone

Abortion achieved in 97% (95% CI 90­100%) of cases without resort to other prostaglandin agents Mean induction­abortion time for the studied population was 6.4 hours (95% CI 5.6­7.0 hours). No significant difference was found between routes of administration Geometric mean induction­abortion interval was 6.9 hours (95% CI 5.8­8.4) and 6.9 hours (95% CI 5.8­8.2) in the 600 mg and 200 mg groups, respectively (not significant). Median dose of misoprostol was 1600 micrograms (3 doses) in each group. Analgesic requirements and prostaglandin-related adverse effects similar between groups. Overall, 11.4% of women required surgical evacuation of the uterus as a result of retained placenta No toxicity or maternal morbidity was recorded. In 3 women, onset of labour occurred spontaneously before prostaglandin administration

Authors recommend that, following pretreatment with mifepristone, misoprostol is used as the prostaglandin of choice to induce abortion in the 2nd trimester Dose of mifepristone used in second-trimester abortion can be reduced from 600 mg to 200 mg

Webster et al.

221

70 women 13­20 weeks

600 mg mifepristone or 200 mg mifepristone 36­48 hours prior to misoprostol

Frydman et al.

339

35 women undergoing TOP for fetal or maternal indications at 15­34 weeks

Randomised double-blind study of 150 mg or 450 mg mifepristone as pretreatment prior to prostaglandins

Mifepristone versus Laminaria tents Ho et al. 340 62 women undergoing TOP in 2nd trimester, 14­20 weeks

Prospective randomised comparative trial of: 600 mg mifepristone 36 hours before administration of gemeprost ­ mediumsized Laminaria tent inserted 12 hours before gemeprost Pregnancies in both groups were terminated with vaginal gemeprost, 1 mg every 3 hours up to a maximum of 5 mg/day

Median induction­abortion interval in mifepristone group (7.5 hours) was significantly shorter than that in Laminaria tent group (11 hours) and significantly fewer gemeprost pessaries were required. There was no significant difference in the amount of narcotic analgesia required or incidence of adverse effects between the 2 groups

Mifepristone is more effective than Laminaria tent in shortening the induction­abortion interval in termination of 2nd trimester pregnancies

80

Evidence tables

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions (continued)

Authors Jain and Mishell Ref. 341 Population 68 women 12­22 weeks of gestation with either an intrauterine fetal death (n = 40) or medical or genetic indications for TOP (n = 30) Intervention Women were randomised to receive 200 micrograms misoprostol vaginally every 12 hours with (n = 35) or without (n = 33) intracervical placement of Laminaria concurrently with the 1st dose of misoprostol Results Rate of abortion 24 hours after initiation of treatment was 69.7% in women receiving misoprostol alone and 68.6% in women treated with misoprostol and Laminaria Abortion rates 48 hours after initiation of treatment were 84.8% and 91.4%, respectively, an insignificant difference. There were no significant differences in incidence of fever, vomiting, diarrhoea, or pain Comments Laminaria tents inserted concurrently with the first dose of misoprostol do not significantly improve the abortifacient effect of vaginal misoprostol in 2nd trimester of pregnancy

Misoprostol versus gemeprost el-Refaey et al. 342 60 women 13­20 weeks of gestation pretreated with mifepristone 600 mg

Dickinson et al.

343

100 women 14­28 weeks of gestation

Misoprostol 400 micrograms orally (up to 3 doses) followed by gemeprost vaginal pessary 1 mg up to 2 doses Gemeprost vaginal pessary 1 mg up to 5 doses A prospective randomised, double-blind, controlled clinical trial of 1 mg gemeprost 3 hourly for 5 doses or 200 micrograms misoprostol 6 hourly for 4 doses, intravaginally The therapeutic regimens were repeated if undelivered by 24 hours

No significant differences between 2 groups in any of the main outcome measures

Nuutila et al.

344

81 women 12­24 weeks of gestation

Group A: 100 micrograms misoprostol intravaginally at 6-hourly intervals (n = 27) Group B: 200 micrograms misoprostol intravaginally at 12-hourly intervals (n = 26) Group C: 1 mg gemeprost intravaginally at 3-hourly intervals (n = 28) Regimens continued until abortion or for 36 hours

Eng and Guan

345

50 women 13­26 weeks

Prospective, randomised study of intravaginal misoprostol (200 micrograms 3-hourly, maximum of 6 doses versus gemeprost 1 mg 3-hourly, maximum of 5 doses

Delivery within 24 hours occurred in 75.1% of women receiving gemeprost and 74.9% receiving misoprostol (NS). Median time from prostaglandin commencement to delivery was similar: gemeprost 13.7 hours versus misoprostol 16.9 hours (NS) NS = not significant. Significant reduction in incidence of vomiting in women randomised to misoprostol occurred (34% versus 13.2%). No significant difference in incidence of maternal fever > 37·5°C, nausea, diarrhoea or placental retention Final rates of terminations 74% in group A; 92% in group B; 89% in group C. Abortion was complete in 37%, 61%, and 32% in each group, respectively (P = 0.03, when group B was compared with the 2 other groups). Induction ­ abortion interval was longer (P = 0.001) in misoprostol groups than in gemeprost group. Less pain (P = 0.01), diarrhoea (P =.001) and vomiting (P = 0.01) in misoprostol groups than in gemeprost group. Mean blood loss in misoprostol groups was lower than in gemeprost group (P = 0.001) 84% in misoprostol group aborted versus 68% in gemeprost group within 24 hours after initiation of therapy. In misoprostol group, abortion rate was influenced by gestational age with 100% abortion rate for those > 17 weeks of gestation compared with 67% for those with a gestational age of 13­16 weeks. Adverse effects were rare in both groups and no major complications were reported in either group

Intravaginal misoprostol performs as effectively as gemeprost in achieving delivery in the second trimester without increase in adverse effects and displaying a significant cost advantage

Intravaginal application of 200 micrograms misoprostol at 12-hourly intervals in induction of 2nd-trimester abortion is equally effective as a standard gemeprost regimen Misoprostol causes fewer adverse effects and is cheaper and more practical to use

Misoprostol was at least as effective as gemeprost as an abortifacient for intrauterine death in 2ndtrimester pregnancy. It was also less costly and had few adverse effects

81

The Care of Women Requesting Induced Abortion

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions (continued)

Authors Ho et al. Ref. 346 Population 50 women 14­20 weeks Intervention 200 mg mifepristone given 36­48 hours before administration of prostaglandins: Group A (n = 25): 400 micrograms oral misoprostol every 3 hours, up to 5 doses Group B (n = 25): 1 mg vaginal gemeprost every 6 hours, up to four doses Prospective randomised trial: Group A: 1 mg vaginal gemeprost every 3 hours for a maximum of 5 doses in 1st 24 hours Group B: 400 micrograms vaginal misoprostol every 3 hours for a maximum of 5 doses in 24 hours Results No significant difference in median induction­abortion intervals (8.7 hours in group A; 10.8 hours in group B) or incidence of adverse effects between 2 groups Comments Misoprostol is as effective as gemeprost in termination of 2nd-trimester pregnancy when combined with mifepristone

Wong et al.

347

70 women 14­20 weeks

Median induction­abortion interval in vaginal misoprostol group was significantly shorter than that in gemeprost group (14.1 hours versus 19.5 hours); percentage of women who achieved successful abortion within 24 hours in misoprostol group was significantly higher than that in gemeprost group (80.0% versus 58.6%). No significant difference in incidence of adverse effects between groups except for diarrhoea, which was more common in gemeprost group. Incidence of fever was more common in misoprostol group Rate of successful abortions within 24 hours 81% with PGE2 and 89% with misoprostol (P = 0.47). All women who received misoprostol had successful abortions within 38 hours. Among those who had an abortion within 24 hours, mean interval from treatment to abortion similar in both groups (10.6 hours with PGE2 and 12.0 hours with misoprostol: NS). Rate of complete abortion 32% for PGE2 and 43% for misoprostol (NS) Adverse effects in those more frequent in women receiving PGE2 than receiving misoprostol In group A, all women aborted within 28 hours and 80% within 20 hours. Medical TOP was complete in 65% of cases In group B, all women aborted within 20 hours, 90% within 13 hours. Medical TOP was complete in 85% of cases. Induction­abortion intervals for group A and B were 16 ± 5.9 hours and 10.3 ± 4 hours, respectively (SS). The incidence of prostaglandin-associated pyrexia, vomiting and diarrhoea were significantly increased in group A (SS). Abdominal pain similar in both groups. No postabortive haemorrhage or infection

Vaginal misoprostol is more effective than gemeprost in termination of 2nd-trimester pregnancy

Misoprostol versus other prostaglandins Jain and 212 55 pregnant Prospective, randomised Mishell women trial of intravaginal 12­22 weeks misoprostol 200 of gestation micrograms every 12 who were hours versus prostaglandin undergoing E2 20 mg intravaginally TOP for either every 3 hours intrauterine fetal death (n = 37) or medical or genetic reasons (n = 18)

Misoprostol is at least as effective as PGE2 for TOP in 2nd trimester involving either a dead or a living fetus, but it is easier to administer and is associated with fewer adverse effects. It is also less costly NS = not significant

Ghorab and El-Helw

348

40 women undergoing TOP for congenital abnormalities or intrauterine fetal death 16­24 weeks

Group A: extra-amniotic prostaglandin F2 Group B: intracervical misoprostol

Intracervical administration of misoprostol appears to be effective and well tolerated with fewer adverse effects and no complications. Larger, randomised comparative studies should be carried out to assess its potential advantages SS = statistically significant.

82

Evidence tables

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions (continued)

Authors Yapaar et al. Ref. 349 Population 340 women with poor cervical condition (Bishop score 4) undergoing TOP 14­28 weeks of gestation Intervention Prospective randomised study: Group A: extra-amniotic ethacridine lactate (n = 82) Group B: intracervical PGE2 gel (n = 100) Group C: intravenous infusion of concentrated oxytocin (n = 36) Group D: vaginal misoprostol (n = 49) Group E: balloon insertion (n = 73) Misoprostol 200 micrograms intravaginally every 12 hours Concentrated oxytocin plus low-dose vaginal PGE2 suppositories (10 mg every 6 hours) Results Abortion within 48 hours in groups A to E were achieved in: A ­ 98.8%; B ­ 90%; C ­ 97.3%; D ­ 77.5%; E ­ 97.2%, respectively Overall median induction­abortion interval ± SD (in hours) in each of groups A to E were as follows: 15.7 ± 9.6; 20.0 ± 14.5; 12.2 ± 14.4; 24.0 ± 22.2; 16.0 ± 15.4 Comments In comparison with the 5 methods, use of extraamniotic ethacridine, intravenous concentrated oxytocin and balloon was found to provide more effective treatment than intracervical PGE2 and misoprostol in terms of achievement of abortion within 24 and 48 hours

Owen and Hauth

350

Success defined as an induction­ delivery interval <24 hours. Analysis of 1st 30 (15 misoprostol, 15 concentrated oxytocin) women found that misoprostol was associated with a lower success rate (67% versus 87%, NS), a longer induction­delivery interval (22 hours versus 18 hours, NS), a higher rate of retained placenta requiring curettage (27% versus 13%, NS) and a higher live birth rate (50% versus 0%)

Misoprostol administered as vaginal tablets in a dose of 200 micrograms every 12 hours was not satisfactory for midtrimester TOP in an unselected population NS = not significant

Gemeprost versus other prostaglandins Kjolhede et al. 351 40 women Open prospective 13­22 weeks randomised study of gemeprost pessaries (n = 20) or dinoproston gel intracervically (n = 20) intracervically All women were pretreated with a 3-mm diameter Laminaria tent applied intracervically for about 4 hours

Cameron and Baird

219

Andersen et al. 352

Success rate 95% for gemeprost and 75% for dinoproston within approximately 48 hours Median abortion time calculated from insertion of Laminaria tent for successful cases was 22 hours for gemeprost and 24 hours 5 minutes for dinoproston (NS). Difference between dinoproston and gemeprost in parous women was statistically significant. No significant difference was found in demand for pethidine or in infection rate between groups. No major adverse effects of treatment were found 120 women Open randomised trial Success rates 77% and 79% for requesting TOP of gemeprost vaginal pessary and infusion groups, 12­16 weeks pessaries and extrarespectively; these rates were of gestation amniotic infusion of PGE2 unaffected by parity. No significant difference in cumulative abortion rate between groups. No differences in induction­abortion interval, nor in time taken to onset of pain or bleeding. Adverse effects, experienced both during treatment and during 6 weeks after abortion, were similar in both groups 152 women Open, randomised, 24-hour success rate 81% in 12­25 weeks controlled 6-centre study gemeprost and 64% in the PGF2 of gemeprost 1 mg vaginal group (P < 0.02). Mean abortion pessaries at 3-hourly times 14.3 hours in gemeprost and intervals, up to a 14.8 hours in PG2 groups. Mean maximum of 5 mg (n = 75) time to onset of pain was shorter versus a single 40-mg and more women experienced blood intra-amniotic dose of loss over 100 ml during induction PGF2 (n = 66) in PGF2 group than in gemeprost group (P < 0.02). Nature and severity of other adverse effects were comparable between groups

Gemeprost seems to be most appropriate of 2 noninvasive methods because of a 95% success rate within 48 hours but also due to its simplicity in design NS = not significant

Gemeprost vaginal pessaries are an effective alternative to the extraamniotic infusion of PGE2 for TOP in early 2nd trimester

Gemeprost had significantly better efficacy and was easier and safer as compared with the PGF2 treatment

83

The Care of Women Requesting Induced Abortion

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions (continued)

Authors Waldron et al. Ref. 353 Population 58 women requesting TOP 14­20 weeks Intervention Results No significant difference in induction­delivery interval for t2 groups. With the exception of an increased incidence of diarrhoea in gemeprost group, there was no significant difference in other adverse effects, analgesia requirements or retained placenta Comments Gemeprost pessaries are an effective alternative to more invasive methods previously used for induction of 2nd-trimester TOP

Mink et al.

354

Open, randomised singlecentre trial of: gemeprost (16,16 dimethyl-PGE1methyl ester) pessaries versus intra-amniotic injection of PGF2 combined with hypertonic saline, intravenous oxytocin and a hygroscopic cervical dilator (Dilapan®) 68 women Dinoprost-containing gel who required (500 micrograms) in TOP 14­33 intracervical application weeks because in a tylose-gel in 6­8 of a severe hourly intervals maternal Gemeprost-containing disease or a vaginal suppository (1 mg) fetal in 12-hourly intervals abnormality

Abortion was induced in 75% of cases within 24 hours, in 89% within 36 hours using gemeprost Mean induction time for gemeprost was 19.5 hours Using dinoprost only 19% of women had an abortion within 24 hours (44% within 36 hours, respectively), mean induction time was significantly longer (38.8 hours, P < 0.005) Additional systemic administration of Sulprostone® was necessary in 21% of cases using gemeprost and in 5% of cases using dinoprost. Severe complications did not occur and minor adverse effects such as nausea or vomiting were observed in single cases

Gemeprost can be used in cervical priming, even after 14 weeks of pregnancy; longer application interval of 12 hours results in a reduction of adverse effects without a decrease in efficacy

Varying doses of gemeprost Armatage and 355 100 women Luckas 12­20 weeks

Thong and Baird

356

100 women requesting TOP 12­19 weeks

Median abortion interval in group A versus B: 16 hours versus 15 hours Cumulative abortion rates in groups A and B: 98% versus 91.8% The 6-hourly group required a significantly lower total dose of gemeprost to induce abortion. There was no difference in rates of adverse effects but those receiving pessaries every 6 hours required less analgesia 36 hours after treatment Median abortion interval: slightly with 200 mg mifepristone, shorter in 1-mg group (7.8 hours women were allocated at versus 8.4 hours, P = 0.5) random to receive either: Cumulative abortion rates at Group A: 4 x 1 mg 24 hours: 98% versus 96% gemeprost by vaginal Women in Group A required pessary every 6 hours significantly more gemeprost to (n = 50) induce abortion than women in Group B: 4 x 0.5 mg Group B gemeprost by vaginal Parous women in both groups pessary every 6 hours required significantly less of the (n = 50) prostaglandin to induce abortion If abortion had not In Group B, median abortion interval occurred after 24 hours, significantly longer in primigravidae 5 x 1 mg of gemeprost than multigravidae (9.5 versus was administered every 6.1 hours; P < 0.02) 3 hours to both groups of There were no significant differences women between groups in incidence of vomiting, diarrhoea or request for analgesia

Group A: gemeprost pessary every 3 hours Group B: gemeprost pessary every 6 hours Maximum of 5 doses

This study found no advantage in giving gemeprost every 3 hours

In parous women, dose of gemeprost can be reduced to 0.5 mg every 6 hours within the first 24 hours without loss of clinical efficacy

84

Evidence tables

Evidence table 14. Studies comparing various agents used in second-trimester medical abortions (continued)

Authors Thong and Baird Ref. 357 Population TOP 12­18 weeks Intervention Open trial of: 5 x 1 mg gemeprost every 3 hours (n = 50) 4 x 1 mg gemeprost every 6 hours (n = 50) Significantly fewer pessaries were required to induce abortion in 6-hour gemeprost group (P < 0.01) Results Median abortion interval was slightly shorter in the 3-hourly group. Cumulative abortion rates at 24 hours were similar (88% versus 82%). In women who aborted within 1st 24 hours, significantly fewer pessaries were required to induce abortion in 6-hour treatment group than the 3-hour group. Parous women in both treatment groups required fewer pessaries to induce abortion than did nulliparous women. No significant differences between groups regarding incidence of diarrhoea, vomiting or the request for analgesia Comments Results suggest that number of pessaries used to induce mid-trimester abortion could be reduced by lengthening interval between insertion of pessaries within the 1st 24 hours, without loss of clinical efficacy

Others Ho et al.

358

Thong and Baird

359

Median induction­abortion interval in vaginal group was significantly shorter than that in oral group (9 versus 13 hours) Percentage of women aborting within 24 hours in vaginal group was significantly higher than that in oral group (90% versus 69%) Median amount of misoprostol used in vaginal group also was significantly less than that in oral group (600 micrograms versus 1000 micrograms). No significant difference in incidence of adverse effects between groups except for fatigue and breast tenderness, which were more common in oral group 76% of women preferred oral route and 24.5% of women preferred vaginal route 98 women for A randomised study of: In 1st 24 hours after administration TOP 12­18 ­ mifepristone + gemeprost of gemeprost, 95%, 85% and 72% weeks of ­ dilapan + gemeprost of women aborted in the mifepristone, gestation ­ gemeprost alone: dilapan and the control groups, a single course of respectively. Median induction­ 4 x 1 mg gemeprost abortion interval in mifepristone pessaries was administered group (6.6 hours) was significantly every 6 hours. shorter than other groups and fewer If abortion had not pessaries were required to induce occurred after 24 hours, abortion. Incidence of diarrhoea and a further course of vomiting lower in mifepristone than 5 x 1 mg pessaries was other groups administered every 3 hours over the next 24 hours

98 women 14­20 weeks

36­48 hours after oral administration of 200 mg of mifepristone, women were given either oral or vaginal misoprostol 200 micrograms every 3 hours for a maximum of 5 doses in 1st 24 hours. Women receiving oral misoprostol also were given a vaginal placebo (vitamin B6), whereas those receiving vaginal misoprostol were given an oral placebo. If they failed to abort, a second course was given by the same route

Vaginal misoprostol was more effective than oral misoprostol in TOP of 2nd-trimester pregnancy after pretreatment with mifepristone. However, more women preferred oral route

Mifepristone in combination with gemeprost is efficacious and this regimen is associated with fewer gastrointestinal adverse effects

85

The Care of Women Requesting Induced Abortion

Evidence table 15. Use of oxytocic agents to reduce blood loss at the time of surgical abortions

Study Garrioch et al. Ref. 360 Population 103 women admitted for outpatient vaginal TOP; most women at 9­12 weeks Intervention Relationship investigated between use of ecbolics and blood loss, vomiting and other adverse effects Group treatments given at onset of cervical dilation were either: ­ physiological saline 2 ml ­ oxytocin 5 iu ­ Syntometrine® ­ ergometrine 5 mg Results and conclusions Randomised controlled trial; staff blind to trial code; method of allocation not described; no power calculation described. Most data shown as points on graph. General anaesthesia was induced with methohexitone, nitrous oxide and oxygen and additional methohexitone if required Patient self-rating was incorporated with study for comparative purposes. Use of combined preparation of oxytocic and ergometrine resulted in lowest blood losses. Ergometrine administered alone was associated with immediate nausea and vomiting but no delayed effects This randomised double-blind trial lacks written numerical detail and does not have the power to detect differences in blood loss between groups of more than about 30%. Syntometrine was significantly more effective than saline or either of other two treatments. Oxytocin was more effective than saline. Ergometrine alone, although associated with smaller mean loss, was not significantly different from saline Randomised controlled trial allocated by sealed envelopes. No power calculations (but powerful enough to detect a difference in blood loss of 25% with 95% confidence) Anaesthesia was standardised and surgery was performed by a single-handed gynaecologist, who assessed size of uterus and graded uterine contractions. All patients received a Cervagem® vaginal suppository 70­270 minutes before surgery. Median blood loss in Syntocinon group (n = 30) was 17.6 ml (range 6.1­72.7) and was significantly less than in placebo group (n = 34), median blood loss 24.5 ml (range 6.7­94.3; P = 0.02), representing a 28% reduction

Ali and Smith

361

64 pregnant women > 9 weeks undergoing elective vaginal TOP

Women allocated randomly to 1 of 2 groups to receive either 10 units of Syntocinon® (1 ml) or 1 ml of saline (placebo) after cervical dilatation

86

References

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Index

ABO blood group assessment 37 Abortion Act 1967 14­15 conscientious objection 16­17 grounds for abortion 15 About Abortion Care (RCOG) 28 abuse, child 19­20 access to abortion services 7, 22­3 inequalities in 1, 2­3 accreditation standards 63­4 Adults with Incapacity (Scotland) Act 2000 18 after care 13, 59­62 audit standards 64 age of consent 18­19 Age of Legal Capacity (Scotland) Act 1991 19 anaesthesia 11, 48­9, 70 analgesia 13, 57­8 antibiotic prophylaxis 10, 40­3 anti-D immunoglobulin 13, 59 aromatherapy 58 audit standards 63­4 azithromycin 10, 41, 42­3 bacterial vaginosis 32, 41, 42 best interests, non-competent adults 18 Birth Control Trust 3, 24, 60 blood tests, pre-abortion 9, 37­8 blood transfusion 38 breast cancer 9, 32­3, 67 British Medical Association (BMA) 17, 18, 19 British Pregnancy Advisory Service (bpas) 26, 46 burial 21 caesarean section, previous 31 capacity to give consent 17, 18­19 certification, abortion 14 cervical cytology 9­10, 38­9 cervical priming for surgical abortion 11, 50­2, 71­5 cervical trauma 8, 31, 51, 66 child abuse 19­20 Chlamydia trachomatis 32, 41 antibiotic prophylaxis 41, 42 screening 41, 42 clindamycin 42 clinic, dedicated 8, 25 clinical guideline see guideline, clinical Communication Standards in Gynaecology: Surgical Procedures (RCOG) 28 competent adults 17 competent minors 18­19 complications and sequelae of abortion 4, 8­9 degrees of risk 30 evidence tables 65­9 gestational age and 23, 65 information for women 29­35, 60 Confidential Enquiry into Maternal Deaths (CEMD) 39 confidentiality 16, 19, 29 conscientious objection 16­17 consent to treatment 17­19 competent adults 17 minors 18­19 non-competent adults 18 contraception 3 post-abortion 13, 60­2 counselling implications 36 post-abortion 60 pre-abortion 36­7 support 36 therapeutic 37 cremation 21 crossmatching 38 daycase care 26 decision, abortion 9, 36­7

101

The Care of Women Requesting Induced Abortion

dilatation and evacuation (D&E) 11, 49­50 complications 49­50, 66 disposal of fetal tissue 20­1 doxycycline 10, 41, 42­3 Duties of a Doctor (GMC) 16 Early Abortions (fpa) 60 ectopic pregnancy 32, 35 emergency grounds for termination of pregnancy 15 ethical aspects 14­21 evidence levels 5 synthesising 5 failed abortion 9, 31­2 family, consent issues 18, 19 Family Law Reform Act 1969 18 Family Planning Association (fpa) 14, 24, 28, 60 fentanyl, intravenous 48, 49 fetal abnormality 1 fetal tissue, disposal 20­1 feticide, prior to late abortion 43 first-trimester abortion medical methods 52­5, 76­9 surgical methods 45­9 followup 13, 60 Fraser criteria 18­19 gemeprost cervical priming for surgical abortion 11, 51 medical abortion 12, 53, 54­5, 57 General Medical Council (GMC) 16, 17 genital tract infection, post-abortion see infection, post-abortion gestational age at abortion 2 abortion method and 45 complications risk and 23, 65 legal aspects 15, 21, 44 ultrasound assessment 39­40 Gillick case 18 gonorrhoea (Neisseria gonorrhoea) 32, 41, 42 good professional practice 16 grounds for abortion, statutory 15 guideline, clinical aim 3 definition 3 implementation and review 6 methods of development 4­6 users targeted 3­4 gynaecological patients, other 8, 26 haemoglobin concentration 37 haemorrhage contingency planning 38 fetomaternal 59 risk 8, 30 health definition 15 risk, as grounds for abortion 15 Healthcare Commission (formerly National Care Standards Commission) 24­5 hepatitis B immunisation 38 histopathology 13, 58 HIV testing 37 home medical abortion 25 hormonal contraception 61 HSA4 notification form 14, 16 Human Fertilisation and Embryology Act 1990 14, 15 incapacitated adults, consent issues 18 incest 19­20 independent sector places, approval 24­5 infection, post-abortion prevention 10, 40­3 risk 9, 32 screen and treat strategy 41, 42 infertility (subfertility) 32, 33­4, 35, 68 information for women 8­9, 28­35 audit standards 63 national 28 post-abortion 13, 60 service provision 22 written 28 inpatient care 26 International Federation of Gynecology and Obstetrics (FIGO) 3 intrauterine contraception 13, 60, 61­2 late abortion disposal of fetus 21 feticide prior to 43 service provision 44 leaflets, information 28

102

Index

legal aspects 14­21 literature search strategy 4 sifting and reviewing 4­5 local anaesthesia 48, 70 local authority, in care of 19 lorazepam, intravenous 49 manual vacuum aspiration (MVA) 46 vs electric 49, 70 vs medical abortion 46 see also suction termination Marie Stopes International 46 maternal deaths 39 medical abortion 11­12, 52­7 analgesia 13, 57­8 early (up to 9 weeks) 52­5, 76­9 failure rate 31­2 gestation band and 45 late first trimester (9­13 weeks) 55 mid-trimester 56­7, 80­5 settings 25, 26, 27 vs surgical abortion 46, 53­4, 55 Medical Defence Union (MDU) 17, 18, 19 mental health risk, as grounds for abortion 15 sequelae of abortion see psychological sequelae methods of abortion see procedures, abortion methotrexate 53 metronidazole 10, 40, 41, 42 midazolam, intravenous 48, 49 mid-trimester abortion see second-trimester abortion mifepristone first-trimester abortion 11­12, 52, 53, 54, 55 mid-trimester abortion 12, 56­7 minors competent 18­19 non-competent 19 miscarriage 34 misoprostol cervical priming for surgical abortion 11, 50, 51­2 first-trimester abortion 12, 52, 53, 54­5 mid-trimester abortion 12, 56­7 National Institute for Clinical Excellence (NICE) 37 National Strategy for Sexual Health and HIV 3, 24, 37 Neisseria gonorrhoea (gonorrhoea) 32, 41, 42 NHS-funded abortion 1, 2 non-competent adults 18 non-competent minors 19 non-steroidal anti-inflammatory drugs (NSAIDs) 57, 58 Northern Ireland 1, 14 notification form (HSA4) 14, 16 Nursing and Midwifery Council 52 Code of Professional Conduct 16, 17 opiate analgesia 57, 58 oral contraceptive pill, combined 61 oxytocic agents 86 paracervical block 48 paracetamol (acetaminophen) 57 parents, consent issues 18­19 partner, rights of 20 pathology 13, 58 peer review 6 pelvic inflammatory disease 32, 41 placenta praevia 34 post-abortion care see after care pre-abortion management 9­10, 36­43 audit standards 63 pregnancy failure to terminate 9, 31­2 future 9, 33­5, 68 unwanted 3 preterm birth 33, 34, 68 private sector places, approval 24­5 procedures, abortion 10­13, 44­58 audit standards 63­4 availability and choice 10, 44 see also medical abortion; surgical abortion progestogen-only contraception 61 prostaglandin first-trimester abortion 11­12, 52, 53 mid-trimester abortion 12, 56 see also gemeprost; misoprostol protocols, local 4 psychiatric disorders 69 psychological sequelae 9, 13, 35, 60, 69

103

The Care of Women Requesting Induced Abortion

recommendations forming and grading 5­6 grading scheme 6 summarised 7­13 red cell antibodies, screening 37 referral to abortion services 7, 22­3 reproductive outcomes, future 9, 33­5, 68 rhesus prophylaxis 13, 59 rhesus status, assessment 37 Royal College of Nursing (RCN) 20 Royal College of Obstetricians and Gynaecologists (RCOG) 2, 3, 28 Scotland abortion services 1, 2 legal issues 18, 19 search strategy, literature 4 second-trimester abortion medical methods 80­5 other methods 50 settings 26, 27 surgical methods 45, 49­50 see also late abortion sedation, conscious 11, 48­9 sequelae of abortion see complications and sequelae of abortion services, abortion 7­8, 22­7 access and referral to 7, 22­3 audit and accreditation standards 63 availability of abortion methods 10, 44 inequalities in access 1, 2­3 settings 8, 23­7 waiting times 7, 23­4 settings, abortion care 8, 24­7 sexual health services 2­3 sexually transmitted infections 41 spouse, rights of 20 statutory grounds for abortion 15 sterilisation, female 13, 61, 62 stillbirths 21 subfertility see infertility suction termination 10­11, 45, 47­9 anaesthesia 48­9 complications 66 electric vs manual 49, 70 gestations below 7 weeks 10, 45­7 manual see manual vacuum aspiration suicide 69 support, decision making 36­7 surgical abortion 10­11, 45­52 anaesthesia 11, 48­9 analgesia 13, 57­8 cervical priming see cervical priming for surgical abortion failure rate 31 first-trimester 47­9 gestation band and 45 mid-trimester 49­50 oxytocic agents to reduce blood loss 86 very early (below 7 weeks) 10, 45­7 vs medical abortion 46, 53­4, 55 see also suction termination surgical evacuation, after mid-trimester medical abortion 56 Termination of Pregnancy for Fetal Abnormality (RCOG) 43 Thorpe, Mr. Justice 17, 18­19 ultrasound scanning during D&E 49­50 pre-abortion 10, 39­40 unlicensed drug regimens cervical priming for surgical abortion 11, 50, 51­2 medical abortion 12, 52, 55, 56 uterine perforation 8, 30, 51, 66 uterine rupture 8, 30­1 vacuum aspiration see suction termination vulnerable people 19­20 waiting times 7, 23­4 wards of court 19 World Health Organization (WHO) definition of health 15 Medical Eligibility Criteria for Contraceptive Use (WHOMEC) 61 multicentre trials 54, 78 Technical and Policy Guidance on Safe Abortion 3, 51 young people aged 16­17 years 18 aged under 16 years 18

104

Information

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