Accuracy of assessment of pregnancy duration by women seeking early abortions.

BACKGROUND: Advances in medical abortion might allow women seeking early abortions to terminate their pregnancies safely and effectively without medical supervision. We investigated whether such women can calculate pregnancy duration accurately, a key step in unsupervised use. METHODS: 422 women seeking first-trimester abortions in two clinics (Pune, India, and Atlanta, USA) used a simple worksheet and calendar to calculate the duration of gestation from the date of last menstrual period (LMP) and/or of unprotected intercourse. Clinicians then used standard clinic practices to estimate pregnancy duration. We compared the two sets of estimates, focusing on women who fell into the "caution zone" (ie, had pregnancy durations >8 weeks according to providers, but < or =8 weeks by their own estimates). FINDINGS: The participants were generally representative of the women seeking abortion at the two clinics. 217 (97.7%) of 222 women in Atlanta and 173 (86.5%) of 200 in Pune could produce an estimate of pregnancy duration. Most (85.4% in Atlanta; 93.6% in Pune) of these estimates were within 2 weeks of those made by providers. For estimates based on LMP, only 10.0% (exact 95% CI 6.2-15.0) of women in Atlanta and 9.8% (5.8-15.3) in Pune fell into the caution zone. For estimates based on a date of intercourse, just 7.7% (4.0-13.1) of women in Atlanta and 3.4% (0-17.8) in Pune fell into the caution zone, although fewer women could use this method. INTERPRETATION: The vast majority of women seeking first-trimester abortion in this study could accurately calculate pregnancy duration within a margin of error clinically inconsequential for safe use of unsupervised medical abortion.

Misoprostol used alone for the termination of early pregnancy. A review of the evidence.

Increased access to medical methods of abortion could significantly reduce maternal mortality, especially in developing countries. In light of the political and commercial difficulties in distributing the abortifacient mifepristone, the widely studied mifepristone-misoprostol regimen may not be sufficiently available in the near future. Thus, researchers have begun to look for alternative regimens, including regimens using misoprostol alone. This article reviews the current available evidence on the potential of a misoprostol-alone regimen for medical abortion. Although the data are varied and difficult to compare, recent studies indicate that a misoprostol-alone regimen could be safe and effective as a method of medical abortion. Misoprostol is widely marketed around the world for its other indications and is inexpensive, stable in tropical climates, easy to transport, and simple to administer. A misoprostol-alone regimen of medical abortion could thus greatly improve the access to safe medical abortion services by women in developing countries.

PIP: Studies have been conducted to examine the potential of misoprostol alone for early termination of pregnancy. These studies were done by Norman et al. (1991), Creinin and Vittinghoff (1994), Bugalho et al. (1996), Koopersmith and Mishell (1996), Carbonell et al. (two studies: 1997, 1998), and Jain et al. (1998). The designs, population sampling methods and regimens varied from study to study. Thus, comparison of results has been difficult. Overall, though, findings indicate that a misoprostol-alone regimen could be safe and effective as a method of medical abortion. This regimen could greatly improve access to safe medical abortion services for women in developing countries, which in turn would lead to a significant reduction in maternal mortality.

Mifepristone-misoprostol medical abortion: home administration of misoprostol in Guadeloupe.

Mifepristone-misoprostol medical abortion promises to revolutionize reproductive health-care. Several simplifications of the standard three clinic visit regimen may be possible, however. Particularly in developing countries, access to the method can be greatly increased by eliminating the longest clinic visit. Indeed, shortly after mifepristone's introduction in Guadeloupe, a semi-developed Caribbean territory administered by France, in 1991, two of the authors conducted a small prospective study of a one treatment-visit regimen. The study regimen was subsequently adopted as the standard of care for medical abortion on the island. Women (n = 92) with amenorrhea of < or = 49 days received 600 mg mifepristone under clinical supervision and were given 400 micrograms oral misoprostol for home administration 2 days later, returning 2 weeks later for follow-up. The success rate (95.4%) is comparable to rates found when both drugs are administered in the clinic and to rates from a similar study conducted recently in the United States. Adverse events were also comparable to protocols requiring in-clinic administration of misoprostol. Protocol adherence appeared to be excellent and loss to follow-up was rare. We suggest that home administration of misoprostol can be safe and effective in most nonindustrialized settings.

PIP: This paper presents a prospective study of home administration and a one-treatment-visit regimen of mifepristone-misoprostol for medical abortion in Guadeloupe. The administration of this contraceptive method usually requires a standard 3-clinic visit regimen, which would sometimes lead to discontinuation of the abortion process. The study consisted of 92 medical abortion cases conducted over a 13-month period. The intervention involved a 1-day treatment visit with patients receiving 600 mg of mifepristone and instructions on ingesting 2 tablets (400 mcg) of misoprostol orally after 2 days and another 200 mcg misoprostol if bleeding had not occurred within 6-12 hours. A follow-up was conducted among these women after 10-15 days of initial clinic visit and contraceptive administration. The total success rate was 95.4% in comparison with those who received a 3-clinic visit regimen and the statistical result of a study conducted in the US. Several adverse effects have been associated with the administration of abortive methods, which include bleeding (19.6% in mifepristone users and 68.2% in misoprostol users) and vomiting. Strict monitoring of mifepristone and misoprostol distribution and patient follow-up was ensured by French legislators. The authors conclude that home administration of misoprostol must be made available to women in developing countries.

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.

PIP: In Brazil and other South and Central American countries where abortion is illegal, misoprostol is widely available and commonly used to induce abortion. However, misoprostol is not very effective as an abortifacient agent and can cause fetal abnormalities. The present study reviewed the cases of 42 infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first trimester of pregnancy and then born with a congenital abnormality. 17 children had equinovarus with cranial nerve deficiencies and 10 had equinovarus as part of a more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (5 cases) and terminal transverse limb defects (9 cases). Congenital hydrocephalus was present in 8 children. The most commonly taken dose of misoprostol was 800 mcg (range, 200-16,000 mcg). Greater awareness of the widespread use of misoprostol to induce abortion should lead to public health interventions to prevent teratogenic effects.

Oral methotrexate and vaginal misoprostol for early abortion.

A prospective trial including 300 pregnant women seeking elective abortion was conducted to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 63 days' gestation. Subjects received methotrexate 50 mg orally and were randomly allocated to receive 800 micrograms of misoprostol vaginally 3, 4, or 5 days after administration of the methotrexate. The misoprostol dose was repeated 48 and 96 h later if abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure) and side effects. Complete abortion occurred in 273 of 300 patients (91%, 95%, CI 87, 94%) patients. No significant statistical differences were found in the success rates when misoprostol was given days 3, 4, or 5 after the administration of methotrexate (p = 0.69). Vaginal bleeding lasted 7.1 +/- 3.8 days, spotting 4.1 +/- 2.5 days, and total bleeding 11.2 +/- 4.1 days. Side effects for methotrexate were minimal, whereas, for misoprostol they were mild and transient except for pain. The use of methotrexate and misoprostol together could be an alternative to the intramuscular use of methotrexate or the use of antiprogestins and prostaglandin for medical abortion.

PIP: The safety and effectiveness of oral methotrexate and vaginal misoprostol for early abortion were evaluated in a prospective study of 300 women who presented to the Cuidad de la Habana (Havana, Cuba) for termination of a pregnancy of a gestational age of 63 days or less. All women were given 50 mg of methotrexate at study entry and then were randomly allocated to receive 800 mcg of misoprostol either 3, 4, or 5 days later. If abortion did not occur, misoprostol was readministered 48 and 96 hours later. Complete abortion occurred in 273 women (91%); the success rate was 72% (216 cases) after just one dose of misoprostol. There were no significant differences in abortion rates based on the day on which misoprostol was administered. Vaginal bleeding lasted an average of 7.1 +or- 3.8 days, spotting continued for 4.1 +or- 2.5 days, and total bleeding persisted for 11.2 +or- 4.1 days. Side effects for methotrexate included nausea (9.7%), vomiting (6.7%), dizziness (10.3%), fatigue (6.3%), headache (5.3%), and chills (5.3%). For misoprostol, side effects included nausea (23.0%), vomiting (25.3%), diarrhea (51.7%), dizziness (18.3%), headache (18.0%), chills (60.0%), and pelvic pain (97.3%). All signs and symptoms were of low intensity and short duration, however. These results suggest that combined use of methotrexate and misoprostol represents a feasible alternative to the intramuscular use of methotrexate or of antiprogestins and prostaglandin for medical abortion. The efficacy and safety of this new regimen are very close to those of RU-486, but the cost is considerably less.

Prevalence and clinical correlates of unsuccessful use of drugs to induce menstruation.

Despite its prohibition, illegal abortion is widely practiced in Brazil, with important adverse health consequences. This report aims to document the prevalence and correlates of the unsuccessful use of drugs to "induce menstrual flow" in a cohort of pregnant Brazilian women. In a cross-sectional study, 6,102 pregnant women between gestation weeks 21 and 28 were interviewed in prenatal clinics of the Brazilian National Health Care System from April 1991 to November 1995. When asked "In order to know if you were pregnant, did you take any medication to induce menstrual flow", 874 (14.4%) responded "yes." The most frequently used drugs were herbal teas (41%), estrogens and/or progestogens (30%), and misoprostol (16%). As demonstrated through logistic regression analysis, independent correlates of such use were unplanned pregnancy (odds ratio [OR] 4.3), low educational attainment (OR 3.3), absence of a husband or partner (OR 1.8), number of children (one or more) (OR 1.5), a history of a previous induced abortion (OR 1.4), and use of oral contraceptives at the time (OR 1.4). Misoprostol use occurred in 2.2% of pregnancies, and showed a very strong association with an unplanned pregnancy (OR 16.0), absence of a husband or partner (OR 3.5), and a history of a previous induced abortion (OR 2.2). It was not associated with a history of menstrual irregularity. In contradistinction, the use of medroxyprogesterone was strongly associated with previous menstrual irregularity (OR = 5.0). The use of drugs and teas, many of which are unknown in terms of fetal risk, in early pregnancy to induce menstrual flow is quite common in women in the Brazilian National Health System. Although the objective of such drug use appears to be varied, analysis of the clinical correlates of use suggest attempted abortion to be the principal aim.

PIP: In countries such as Brazil, where abortion is prohibited, a range of drugs are used to induce menstruation. The present study investigated the prevalence and clinical correlates of unsuccessful use of drugs given to pregnant women to start menstrual flow. Enrolled were 6102 pregnant women at gestational weeks 21-28 presenting to the prenatal clinics of the Brazilian National Health Care System in 1991-95. 874 women (14.4%) responded affirmatively to the question, "In order to know if you were pregnant, did you take any medication to induce menstrual flow?" The frequency varied from 6-22% among the seven cities included in the study. The most commonly used drugs were herbal teas (41%), estrogens and/or progestogens (30%), and misoprostol (16%). Significant independent predictors of such medication use included unplanned pregnancy (odds ratio (OR), 4.3), low educational attainment (OR, 3.3), absence of husband or male partner (OR, 1.8), 1 or more living children (OR, 1.5), previous induced abortion (OR, 1.4), and current use of oral contraception (OR, 1.4). Herbal tea and misoprostol use were more strongly associated with unplanned pregnancy than medroxyprogesterone acetate; however, most drug use reported for menstrual induction appeared to be intended to avoid a possible pregnancy. Of concern is the effect of these medications and herbs on fetuses in cases where an abortion attempt is unsuccessful.

Misoprostol 3, 4, or 5 days after methotrexate for early abortion. A randomized trial.

A randomized trial was conducted including 287 pregnant women seeking elective abortion to compare the efficacy of misoprostol given 3, 4, or 5 days after methotrexate for abortion at < or = 63 days' gestation. Subjects received 50 mg/m2 methotrexate intramuscularly and were randomly allocated to self-administer vaginally 800 micrograms of misoprostol 3, 4, or 5 days after the methotrexate. The misoprostol dose was repeated 48 and 96 h later if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), and side effects. Eighty-six cases (93%; 95% confidence interval [CI] 85%-97%) aborted in Group I; 90 cases (92%; 95% CI 84%-96%) aborted in Group II (relative risk [RR] = 1.09; RR 95% CI 0.38-3.14); and 89 (93%; 95% CI 86%-97%) cases aborted in Group III (RR = 0.97; RR 95% CI 0.33-2.87). No significant statistical differences were obtained for the success rates when misoprostol was given days 3, 4, or 5 after the administration of methotrexate (p = 0.97) nor with any of the characteristics of the subjects. Complete abortion occurred in 265/287 (92%; 95% CI 89%-95%) patients. Twenty-two cases (8%; 95% CI 5%-11%) resulted in failure. Side effects for methotrexate were minimal while for misoprostol they were moderate. This combination could be an alternative to surgical abortion or the use of antiprogestins and prostaglandins for medical abortion.

PIP: A randomized trial was conducted including 287 pregnant women seeking elective abortion to compare the efficacy of misoprostol given 3, 4, or 5 days after methotrexate for abortion at 63 days or less gestation. Subjects received 50 mg/sq. m methotrexate intramuscularly and were randomly allocated to self-administer vaginally 800 mcg of misoprostol 3, 4, or 5 days after methotrexate administration. The misoprostol dose was repeated 48 and 96 hours later if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure) and side effects. 86 cases [93%; 95% confidence interval (CI), 85-97%] aborted in Group I; 90 cases (92%; 95% CI, 84-96%) aborted in Group II [relative risk (RR) = 1.09; RR 95% CI, 0.38-3.14]; and 89 cases (93%; 95% CI, 86-97%) aborted in Group III (RR = 0.97; RR 95% CI, 0.33-2.87). No significant statistical differences were obtained for the success rates when misoprostol was given days 3, 4, or 5 after methotrexate administration (p = 0.97) nor with any of the characteristics of the subjects. Complete abortion occurred in 265/287 patients (92%; 95% CI, 89-95%). 22 cases (8%; 95% CI, 5-11%) resulted in failure. Side effects for methotrexate were minimal, while for misoprostol they were moderate. This combination could be an alternative to surgical abortion or the use of antiprogestins and prostaglandins for medical abortion.

Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: a comparative trial of mifepristone-misoprostol versus surgical abortion.

OBJECTIVE: We investigated safety, efficacy, and acceptability of an oral regimen of medical abortion compared with surgical abortion in three developing countries. STUDY DESIGN: Women (n = 1373) with amenorrhea < or = 56 days chose either surgical abortion (as provided routinely) or 600 mg of mifepristone followed after 48 hours by 400 micrograms of misoprostol. This is the appropriate design for studying safety, efficacy, and acceptability among women selecting medical abortion over available surgical services. RESULTS: The medical regimen had more side effects, particularly bleeding, than did surgical abortion but very few serious side effects. Failure rates for medical abortion, although low, exceeded those for surgical abortion: 8.6% versus 0.4% (China), 16.0% versus 4.0% (Cuba), and 5.2% versus 0% (India). Nearly half of failures among medical clients were not true drug failures, however, but surgical interventions not medically necessary (acceptability failures or misdiagnoses). Women were satisfied with either method, but more preferred medical abortion. CONCLUSION: Medical abortion can be safe, efficacious, and acceptable in developing countries.

PIP: A multi-center comparative study of medical compared to surgical abortion confirmed that medical abortion can be safe, effective, and acceptable in developing countries. A total of 1373 women from medical centers in China, Cuba, and India with pregnancies of 56 days' gestation or less were given the choice of surgical abortion or 600 mg of mifepristone followed after 48 hours by 400 mcg of misoprostol. Since the majority selected medical abortion, researchers in China and Cuba assigned some of these women to the surgical group to equalize the size of the two groups. The surgical abortion failure rates in China, Cuba, and India were 0.4%, 4%, and 0%, respectively, while the failure rates for medical abortion were 8.6%, 16.0%, and 5.2%, respectively. In all sites, both medical failures (an adverse effect resulting in a medically indicated surgical intervention) and acceptability failures (failure to complete the entire regimen) contributed substantially to the gross failure rates for medical abortion. Medical abortion failure rates increased with gestational age. Although cramping, nausea, and vomiting were more frequent among women in the medical abortion group and bleeding was heavier, general assessments of well-being reported at exit interviews did not differ between the two treatment groups at any site. Regardless of abortion method, the majority of women were either satisfied or highly satisfied with the procedure. In all countries, a higher number of medical than surgical abortion patients indicated they would opt again for the same procedure. Neither the bleeding pattern nor the higher failure rate associated with medical abortion justify withholding this option from women in developing countries.

Brazil investigates drug's possible link with birth defects.

PIP: In Brazil, many women are using the synthetic prostaglandin misoprostol to induce abortion. Since abortion is illegal in Brazil, they take misoprostol without any medical supervision. It was introduced in Brazil in 1986 as a treatment for gastric ulcers. Its brand name is Cytotec. The prescription drug is widely available on the black market, where the price for 4 200-mg tablets begins at US$100. Use of the drug with failure to abort may be linked to birth defects. A geneticist and a neuropediatrician at the Children's Institute of the Sao Paulo Hospital das Clinicas are studying 9 children with congenital or neurological abnormalities. Physicians in other parts of Brazil are following another 30 children with the same circumstances. A physician in Porto Alegre is following 40 women who took misoprostol but did not abort. As of mid 1994, she had found 3 cases of congenital abnormalities. The Brazilian Society for Clinical Genetics is overseeing an epidemiologic study in 10 major maternity hospitals where researchers will examine all neonates and ask all mothers about the possible use of misoprostol. Staff at the genetics outpatient clinics of 6 leading hospitals are about to conduct a related study among mothers. Both of these studies run the risk of low reporting, since mothers may be disinclined to admit to criminal use of misoprostol. Almost 50% of all women who want pregnancy termination in Brazil use misoprostol. The abortion fails in about 33% of these cases. The evidence suggests an 8-10% risk of abnormalities among women who use misoprostol and experience abortion failure. Ministry of Health sources unofficially appreciate that misoprostol use is reducing the number of women hospitalized with infections caused by abortion attempts with sharp instruments, which in turn has reduced maternal mortality.^ieng

Induction of labor with intravaginal misoprostol in intrauterine fetal death.

OBJECTIVE: Our purpose was to evaluate the effectiveness and safety of intravaginal misoprostol for the induction of labor in intrauterine fetal death. STUDY DESIGN: Seventy-two women at 18 to 40 weeks of pregnancy with intrauterine fetal death, without abdominal scars, were treated with 100 micrograms of intravaginal misoprostol. The dose was repeated every 12 hours until effective uterine contractions and cervical dilatation were obtained, for up to 48 hours. RESULTS: The mean time from induction to delivery was 12.6 hours, and only six patients (8%) required between 24 and 48 hours, at the end of which all patients had been delivered. Only the Bishop's score was significantly associated with time from first dose to expulsion. No surgical procedure was required. Hypercontractility, sweating, fever, diarrhea, or other gastrointestinal effects were not detected. There was no need for analgesics. CONCLUSIONS: Intravaginal misoprostol at the dose of 100 micrograms every 12 hours appears to be a safe, effective, practical, and inexpensive new method for induction of labor in intrauterine fetal death.

PIP: Physicians at the Maputo Central Hospital in Mozambique inserted at least 100 mcg misoprostol into the vaginas of 72 women with intrauterine fetal death at 18-40 weeks pregnancy to induce labor. They inserted another dose every 12 hours up to 48 hours if a patient had not begun labor. The mean time between induction of labor to delivery stood at 12.6 hours. 92% delivered within 24 hours. All had delivered by 48 hours. The time between 1st dose and expulsion was significantly lower for women with a Bishop's score of more than 5 than for those with a score of 5 and lower (7.6 vs. 13.7 hours; p = .028). Bishop's score was the only variable associated with time to expulsion. (It is used to estimate the prospects of labor by evaluating the extent of cervical dilatation, effacement, station of the head, consistency of the cervix, and cervical position in relation to the vaginal axis.) No one died, needed surgery either before or after delivery, or suffered side effects. The physicians noted that this regimen greatly reduced costs, staff workload, and time. These findings suggest that intravaginal misoprostol at a dose of 100 mcg/12 hours is a safe, effective, practical, and inexpensive new way to induce labor in cases of intrauterine fetal death.

The effectiveness of intravaginal misoprostol (Cytotec) in inducing abortion after eleven weeks of pregnancy.

At Maputo Central Hospital in Mozambique, intravaginal misoprostol, a PGE2 methyl-analogue, was used by 169 women whose request for interruption of pregnancy had been approved. The drug was used by women who had completed between 12 and 23 weeks of gestation. The initial dose was 800 micrograms, repeated 24 hours later if abortion had not occurred or was not in progress. The treatment was considered a failure when abortion was not advanced by 48 hours after the initial dose, and curettage was performed in all but one of such cases. During the course of the study, the dosage was successively reduced to 600, 400, and 200 micrograms. Abortion was successfully induced in 154 women (91.1 percent); there were 10 failures (5.9 percent), and five women (3.0 percent) dropped out of the study. The mean time from initial dose to abortion was 14.3 hours. No significant association of success rate and time from dosage to expulsion was found with age, parity, previous abortion, or gestational age. Preventive vacuum aspiration of the uterine cavity was carried out on all subjects.

Women use illicit drug to induce abortion.

PIP: Citing information published in 2 Lancet articles (one by the research groups of Dr. Helena Coelho and Dr. Walter Fonseca and another by Sarah Costa and Martin Vessey), this article describes the misuse of the anti-ulcer prescription drug, misoprostol, which is actually obtainable over the counter, to induce abortion in Brazilian women. Its safety and efficacy are questionable. During a 2.5 year survey, Coelho found that 32% of the women admitted to the main obstetric hospital at Fortaleza had developed womb infections. Others hemorrhaged badly enough to require transfusions. Also, one-third of those who needed womb evacuations had used misoprostol or other illicit drugs to induce the miscarriage. Costa and Vessey discovered that 10% of the women studied who finished their pregnancies had initially attempted to use misoprostol as an abortifacient. Costa blames the lack of access to contraception for the rise in abortion attempts. Changes in prescription laws pertaining specifically to misoprostol have reduced its use in this manner.^ieng

The Brazilian experience with Cytotec.

Cytotec, the commercial name for misoprostol, which is a synthetic analogue of prostaglandin E1, was approved for use in Brazil in 1986 to treat gastric and duodenal ulcers. The drug can and has also been used to induce abortion, which has created controversy in a country in which induced abortion is illegal. A study of the drug was undertaken in 1992 that included analyses of the drug's sales profile, of information published by the media, and of its use from women's and gynecologists' points of view, the latter examined using qualitative methodologies. The analysis of Cytotec's sales volume showed quick growth from its introduction until the first half of 1991, when its use was restricted by the Ministry of Health. For women, Cytotec's main advantages have been that it is relatively inexpensive, convenient to use, and can be used in private. Data obtained from gynecologists show that Cytotec's addition to the obstetric therapeutic arsenal was welcome and also confirmed the drug's influence in reducing the complications of illegal abortions shown in other studies.

PIP: A Brazilian study of 1986-92 sales of the prostaglandin analogue, misoprostol (Cytotec), often used as an abortifacient in Brazil, shows that an increasing trend began in January 1989 and was maintained until July 1991, when the Ministry of Health (MOH) imposed restrictions on Cytotec sales. Cytotec introduced in mid-1986 as a treatment for gastric and duodenal ulcers. Sales reached their lowest levels in 1992 (150,207 vs. 189,199-581,003 annual sales). Other factors contributing to the fall in sales wee reduced production due to an agreement between the manufacturer and MOH, a newspaper campaign by anti-Cytotec groups, and a law for a double-copy prescription. Hospital surveys in the early 1990s indicated that many women used Cytotec to induce an abortion. The media, pharmacies, physicians, women, and the manufacturer spread the news that Cytotec could be used to induce abortion. Women take 4-16 doses of Cytotec to induce abortion, generally during the first trimester. The use Cytotec because it is relatively inexpensive and less traumatic than other abortion methods and can be taken in privacy. Women also consider Cytotec to be safe. Nevertheless, most women complain of the pain they experience and the need to eventually go to a hospital. These negative views are a result of lack of information about the physical process of the drug. Gynecologists of the Sao Paulo public health system confirm the widespread use of Cytotec as an abortifacient. Cytotec allows gynecologists to perform abortions without the police being involved since women induce an abortion with Cytotec, and gynecologists perform a curettage. Hospital staff consider this type of induced abortion more acceptable than other methods. It also allows them to avoid the feelings of inadequacy they experience when women are admitted for an infection caused by a botched abortion or perforated uterus. These findings demonstrate that a favorable atmosphere exists in Brazil to promote the legalization of abortion.

Misoprostol and illegal abortion in Rio de Janeiro, Brazil.

We report on the determinants and consequences of induced abortion among 803 women admitted to hospital with abortion complications in Rio de Janeiro, Brazil, in 1991. 458 (57%) women reported using misoprostol to induce abortion, 74% in the first 4 months of pregnancy. Doses of 200-16,800 micrograms were reported, with a median of 800 micrograms. 65% of the women took the drug orally, 29% used a combination of oral and vaginal routes, and 6% administered it intravaginally. Vaginal bleeding and uterine cramps were the commonest reasons for seeking hospital care. Only 8% of women reported gastrointestinal side-effects. Misoprostol induced vaginal bleeding within 12 h of administration in 52% of the women, but 16% waited 10 days or more for onset of bleeding. 4% were admitted to hospital with complete abortion. The likelihood of bleeding starting within 12 h increased with duration of gestation and it was greater when the drug was used both orally and intravaginally. A significantly smaller proportion of women taking misoprostol than of those who induced abortion by catheter insertion presented signs of infection or physical injuries or required blood transfusion (< 0.0005). Among 803 women interviewed at delivery as controls, 6% had taken misoprostol but abortion had not ensued. Misoprostol has an important role as an abortifacient among the women studied.

Round table on RU486.

PIP: As a non-invasive means of early abortion, RU-486 has the potential to increase women's reproductive options; at the same time, the "abortion pill" has stimulated debate about the ethics and safety of new medical technologies. When combined with a prostaglandin (PG), the success rate for RU-486 is 96% for pregnancies of up to 9 weeks' gestation. In France, over 120,000 women have used RU-486/PG to terminate pregnancy, and this regimen is now used in about 25% of abortions. Clinical trials of RU-486 are underway in Cuba, China, India, Singapore, and Zambia. The Program for Appropriate Technology has identified four considerations for introducing RU-486 to developing countries: whether abortion or menstrual regulation is legal; whether women find the method acceptable and can comply with the multiple visit treatment regimen; whether the health infrastructure can support safe method use, including prevention of misuse and provision of appropriate medical backup personnel and facilities; and whether the cost of the regimen is affordable to individuals and/or programs --conditions unlikely to be met in most such countries. Ideal would be development of a medical abortifacient that is single dose and the lowest possible dose of each drug, provokes miscarriage within a more predictable time frame with less acute and prolonged bleeding, is safe and effective beyond two months, has minimal side effects, and maximizes short-term safety and minimizes long-term effects. Technological advances are being undermined, however, by political and religious attacks on the method. Even some feminists have expressed concerns about potential long-term effects of RU-486 use.^ieng

The "ethics" of RU486.

PIP: The use of RU-486 to induce abortion represents a new era in reproductive technology and merits ethical attention. The feminists principles of concern for women's well-being, paying attention to the specific needs of women in specific circumstances, and balancing risks and benefits can be applied to an examination of RU-486. RU-486 has invoked the image of women's medical empowerment and has been deemed "the moral property of women." Support for RU-486 has come from major international health and feminist organizations, while the opposition of the anti-choice forces has been matched by that of the Feminist International Network of Resistance to Reproductive and Genetic Engineering. Issues critical to the introduction of RU-486 include 1) access and suitability, 2) whether RU-486 increases women's control over reproduction in a safe manner, and 3) the political problems involved when feminist leaders press for testing and attempt to explain varied and even opposing feminist positions in productive ways.^ieng

Is Cytotec an answer?

PIP: Brazilian women's reliance on Cytotec--a prostaglandin commercially marketed for the treatment of gastric ulcers but with abortifacient potential--demonstrates the depth of determination of poor women to control their fertility in countries where abortion is illegal. An estimated 1-4 million clandestine abortions are performed in Brazil each year. After Cytotec's introduction in 1986, sales rose rapidly to 50,000 units/month by 1991. In 1991, however, the Ministry of Health altered the regulations surrounding sales of Cytotec. Its sale was prohibited in 1 state, its use was restricted to hospitals in another, and the remaining states required 2 prescriptions. As a result, sales dropped to 5000 units/month in 1992. At the time these restrictions were enacted, Cytotec was the agent used to introduce half the abortions induced by Brazilian women. Women found this method acceptable because of its low cost, accessibility, and privacy. The major complication of its use, uterine bleeding, is far easier to treat than the uterine perforation and pelvic infections associated with other methods of self-induced abortion. In fact, the improved abortion-related mortality/morbidity statistics in Brazil in recent years are probably a direct result of Cytotec use. Restricted access to this agent is expected to reverse this trend.^ieng

Paraguayan pharmacies and the sale of pseudo-abortifacients.

This study was conducted in 1985 in Asunción, Paraguay, 6 years after the closure of the state supported family planning services. Data from national surveys in 1977 and 1987 permit a comparison of sources of contraceptive supplies before and after the elimination of government support for family planning. The purchase of pseudo-abortifacients from private pharmacies was used as an indication of induced abortion. After the loss of government clinics, it is suggested that some women turned to pharmacists to obtain pseudo-abortifacients when faced with unwanted pregnancy. There is an indication of increased pseudo-abortifacient use, particularly among unmarried women and those from poorer neighbourhoods.

PIP: The hypothesis that a restriction of family planning services will be associated with an increased incidence of abortion was investigated in a survey carried out in Asuncion, Paraguay, in 1985. In 1979, the Government of Paraguay abruptly eliminated all support for family planning services at Ministry of Health clinics--a measure that affected at least half of all contraceptive acceptors and forced them to turn to pharmacies for contraceptive supplies. The survey, which samples 10% of the registered private pharmacies in Asuncion, used the sale of pseudo- abortifacients as a measure of induced abortion. Also interviewed were 56 contraceptive purchasers and 51 purchasers of injectables contraceptives intended for use as abortifacients who were recruited at the participating pharmacies. The results indicated that low-income women were 5 times more likely than their higher income counterparts to purchase pseudo-abortifacients. In addition, unmarried women were 3 times more likely to purchase progestogen injections to induce a missed menstrual period than married women. Almost 70% of abortifacient purchasers reported that they had attempted to self-abort on previous occasions. The pharmacists stated that up to 50 women a week requested medication for pregnancy termination and were in agreement that this practice had increased substantially following the government's withdrawal of support for contraception. The pharmacists expressed concern about the nonavailability of counseling from trained family planning personnel and indicated that some pharmacy staff knowingly exploit women by injecting them with unsafe preparations or drugs that cannot induce abortion. The administration of ineffective pseudo-abortifacients can delay the decision to seek an illegal abortion or result in life-threatening incomplete abortion.

Contraceptive use and fertility in Paraguay, 1987.

In 1987, 38 percent of married Paraguayan women aged 15-44 were practicing contraception, with oral contraceptives being the most prevalent method. Fertility rates for the population were at corresponding levels, with an overall fertility rate of 5.4 births per woman. Fertility has not changed substantially for the nation as a whole since 1979, and contraceptive use has increased by only 6 percentage points. Findings from the present study are consistent with the lack of a public sector family planning program in the country. Pharmacies are the principal source of contraceptives in the country. Twenty-two percent of all women and one-third of married women are at risk of having an unplanned pregnancy. The greatest impact on contraceptive use can be made if new and continued program efforts focus n the interior of the Oriental region of the country.

PIP: In 1987, staff from the International Planned Parenthood Federation affiliate in Paraguay (CEPEP) with technical assistance from the US Centers for Disease Control (CDC) selected 1500 households in metropolitan Asuncion and the interior of the Oriental region (the Interior) to study contraceptive behavior and fertility. Eligible respondents to the survey consisted of women 15 to 44 years old, regardless of marital status. Researchers interviewed only 1 woman per household and completed 2224 interviews. The 1987 overall fertility rate of 5.4 births per woman did not change much since 1979 (4.9), and contraceptive use only increased from 32.1% to 37.6%. Metropolitan Asuncion reported the highest prevalence (more than 50%). In terms of methods to control family size, oral contraceptive (OC) led the list of contraceptive use at 13.5%, followed by native herbs called yuyos at 7.2% and intrauterine devices (IUDS) at 5.1%. After the Paraguayan MOH stopped providing family planning services through MOH facilities in 1979, pharmacies became the primary source of contraceptives (51%). Prior to 1979, the MOH supplied 45% of all contraceptives. Findings in the survey indicated that 22% of all women and 33% of married women are at risk of having an unplanned pregnancy. Also the women exhibited a strong interest in spacing or limiting family size, but because the public sector does not provide contraceptives women cannot do so.

Studies on zoapatle, II. Leucanthanolide, a novel sesquiterpene lactone from Montanoa leucantha ssp. leucantha.

PIP: A sesquiterpene lactone given the trivial name leucanthanolide, from the Mexican zoapatle plant (Montanoa leucantha), long used as an herbal remedy, was isolated and was found to have cytotoxicity but no uterine activity. The compound was isolated from the fraction containing zoapatanol, a substance being investigated for its ability to induce menses, abortion and labor. The compound has a molecular formula of C19H2606, a 5-membered lactone ring, an ester group, and a germacradienolide skeleton. It was evaluated for abortifacient activity in pregnant guinea pigs by intraperitoneal injection on day 22 of gestation. 3 of 5 animals had abnormal fetuses, but there was no evidence of early uterine activity. Cytotoxic testing in vitro was done on KB and P-388 test systems in cell culture. The ED50 of leucanthanolide was 0.57 mcg/ml (KB) and 0.93 (P-388). In comparison, the ethyl acetate fraction had an ED50 of 1.35 mcg/ml and 5.2 mcg/ml respectively.^ieng