Mifepristone Combination Therapy Compared With Misoprostol Monotherapy for the Management of Miscarriage: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess whether mifepristone pretreatment adversely affects the cost of medical management of miscarriage. METHODS: Decision tree analyses were constructed, and Monte Carlo simulations were run comparing costs of combination therapy (mifepristone and misoprostol) with monotherapy (misoprostol alone) for medical management of miscarriage in multiple scenarios weighing clinical practice, patient income, and surgical evacuation modalities for failed medical management. Rates of completed medical evacuation for each were obtained from a recent randomized controlled trial. RESULTS: In every scenario, combination therapy offered a significant cost advantage over monotherapy. Using a Monte Carlo analysis, cost differences favoring combination therapy ranged from 6.3% to 19.5% in patients making federal minimum wage. The cost savings associated with combination therapy were greatest in scenarios using a staged approach to misoprostol administration and in scenarios using in-operating room dilation and curettage as the only modality for uterine evacuation, a savings of $190.20 (99% CI 189.35-191.07) and $217.85 (99% CI 217.19-218.50) per patient in a low-income wage group, respectively. A smaller difference was seen in scenarios using in-office manual vacuum aspiration to complete medical management failures. As patients' wages increased, the difference in cost between combination therapy and monotherapy increased. CONCLUSION: Mifepristone combined with misoprostol is, overall, more cost effective than monotherapy, and therefore cost should not be a deterrent to its adoption in the management of miscarriage.

Trends in misoprostol use and abortion complications: A cross-sectional study from nine referral hospitals in Nigeria.

OBJECTIVE: The study aimed to assess the use of misoprostol and complications associated with abortions in referral hospitals in Nigeria, a country with restrictive abortion laws. METHODS: A cross-sectional study at nine referral hospitals in South-west Nigeria. Nine years' data were retrieved from medical records, including 699 induced abortions. Independent variable was the method of abortion; dependent variables were complications, need for treatment and mortality. Statistical significance was tested with Chi-square, Fishers' exact and chi-square for trend tests (p<0.05). RESULTS: There were 699 induced abortions amongst 2,463 abortions found in records. Nearly 70% were surgical abortions, but misoprostol use significantly increased over the study period in a linear trend (Χ2 trend: 30.96, P <0.001). Patients who used misoprostol were significantly less likely to have infectious morbidity, genital tract injuries or medical complications. There was no difference in incomplete abortion in the groups. Patients were more likely to have in-patient care with surgical abortions (p<0.001), to need prolonged antibiotic regimens (p = 0.003), need further surgeries or additional specialist care (p = 0.009). CONCLUSION: Misoprostol abortion has significantly increased over time, and was associated with less morbidity and need for further treatment, in this study. It appears to be the safer option.

Complications with use of misoprostol for abortion in Madagascar: between ease of access and lack of information.

OBJECTIVE: The objective was to learn what complications some women experienced in Madagascar following use of misoprostol for abortion and what treatment they received post misoprostol use. STUDY DESIGN: This was a qualitative study in 2015-2016 among women who had experienced complications after use of misoprostol, with or without additional methods, for abortion; what information they received before use; what dosage and regimens they used; what complications they experienced; and what treatment they received postuse. We initially conducted in-depth, semistructured interviews with 60 women who had undergone an abortion that resulted in complications. The results presented here are based on interviews with the subset of 19 women who had used misoprostol. RESULTS: The 19 women were aged 16-40, with an average age of 21-26 at interview and average age of 18-21 at abortion. To obtain an abortion, they sought advice from partners, friends, family members, and/or traditional practitioners and health care providers. Misoprostol was easily accessible through the formal and informal sectors, but the dosages and regimens the women used on the advice of others were extremely variable, did not match WHO guidelines and were apparently ineffective, resulting in failed abortion, incomplete abortion, heavy bleeding/hemorrhage, strong pain and/or infection. CONCLUSIONS: This study provides data on complications from the use of misoprostol as an abortifacient in Madagascar. Health care providers need training in correct misoprostol use and how to treat complications. Law and policy reforms are needed to support such training and to ensure the provision of safe abortion services in the public health system. IMPLICATIONS: Health care providers who provide abortion care and treatment of abortion complications need training in correct misoprostol use and treatment of complications. Women and pharmacy workers also need this information. Law and policy reforms are needed to allow training and provision of safe services. Further research is needed on the extent and impact of incorrect misoprostol administration.

Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Significant adverse events and outcomes after medical abortion.

OBJECTIVE: To analyze rates of significant adverse events and outcomes in women having a medical abortion at Planned Parenthood health centers in 2009 and 2010 and to identify changes in the rates of adverse events and outcomes between the 2 years. METHODS: In this database review we analyzed data from Planned Parenthood affiliates that provided medical abortion in 2009 and 2010 almost exclusively using an evidence-based buccal misoprostol regimen. We evaluated the incidence of six clinically significant adverse events (hospital admission, blood transfusion, emergency department treatment, intravenous antibiotics administration, infection, and death) and two significant outcomes (ongoing pregnancy and ectopic pregnancy diagnosed after medical abortion treatment was initiated). We calculated an overall rate as well as rates for each event and identified changes between the 2 years. RESULTS: Among 233,805 medical abortions provided in 2009 and 2010, significant adverse events or outcomes were reported in 1,530 cases (0.65%). There was no statistically significant difference in overall rates between years. The most common significant outcome was ongoing intrauterine pregnancy (0.50%); significant adverse events occurred in 0.16% of cases. One patient death occurred as a result of an undiagnosed ectopic pregnancy. Only rates for emergency department treatment and blood transfusion differed by year and were slightly higher in 2010. CONCLUSION: Review of this large data set reinforces the safety of the evidence-based medical abortion regimen. LEVEL OF EVIDENCE: III.

Medical methods for first trimester abortion.

BACKGROUND: Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH METHODS: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. MAIN RESULTS: Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups. AUTHORS' CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.

Partial foetal retention following aglepristone treatment in a bitch.

This short communication describes the case of partial foetal retention in an 18-month-old female French bulldog following induction of abortion owing to an undesired mating. Abortion was induced with aglepristone administered in two consecutive protocols of a dual injection 1 day apart. After failure of the first treatment to achieve abortion, 15 days later, a second treatment was administered. Delivering of aborted foetus occurred 2 days after the last administration. Five weeks after the abortion, the female showed a weak haemorrhagic vaginal discharge. On ultrasound examination, the presence of uterine wall distension as well as a puppy skull inside the uterus was observed. This clinical case makes clear that although aglepristone is a very reliable drug, follow-up of the female during treatment and in the immediate post-partum is necessary to ensure a good outcome.

One- and two-day mifepristone-misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks of gestation.

OBJECTIVE: To compare the efficacy of 1-day and 2-day mifepristone and misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks. METHODS: A prospective randomized cohort study of 100 women who underwent voluntary termination between 13 and 16 weeks of gestation. Patients were randomly assigned to receive 200mg of oral mifepristone, followed 1 day (group 1) or 2 days (group 2) later by 600 µg of vaginal misoprostol. All patients received 400 µg of oral misoprostol every 6 hours for a maximum of 2 doses. Main outcome measure was successful abortion rate at 24 hours after the start of misoprostol treatment. Secondary outcome measures were induction-to-abortion interval and frequency of adverse events. RESULTS: The 24-hour successful abortion rate was similar between groups 1 and 2 (47 [94%] vs 50 [100%]; P = 0.241). The mean misoprostol-to-abortion interval was also similar (7.0 ± 3.0 vs 6.8 ± 4.3 hours; P = 0.744). Among the 86 patients for whom histological examination of the products of conception was performed, retained chorionic villi rates were higher in the 1-day regimen group compared with the 2-day regimen group (46.2% [18/39] vs 29.8% [14/47]; P<0.001). CONCLUSION: A 2-day mifepristone-misoprostol interval resulted in fewer incomplete abortions than a 1-day interval for second trimester termination of pregnancy between 13 and 16 weeks.

Early termination of pregnancy by single-dose 800 microg misoprostol compared with surgical evacuation.

OBJECTIVES: To assess the efficacy, safety, and acceptability of early termination of pregnancy by vaginal administration of a single dose of misoprostol. SETTING: Healthy women seeking abortion in an institutional research environment in a tertiary-care hospital. DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: One hundred forty women seeking termination of pregnancy up to 49 days' gestational age were alternatively assigned to undergo medical or suction termination. INTERVENTION(S): Saline-soaked prostaglandin E(1) analogue, misoprostol (800 microg), was administered vaginally in group I, and group II underwent suction evacuation. Transvaginal sonography was performed on two subsequent visits to assess outcome. MAIN OUTCOME MEASURE(S): Efficacy, side effects, complications, and acceptability were assessed in both groups. RESULT(S): Complete abortion rate between the misoprostol and the surgical group was 94.2% versus 95.5%, respectively. Side effects were fewer in the misoprostol group and it had a higher acceptability rate. CONCLUSION(S): Single dose of vaginal misoprostol alone has a success rate comparable with surgical method for termination of early pregnancy. Side effects were fewer in women who received misoprostol, and the method was well accepted.

Medical methods for first trimester abortion.

BACKGROUND: Surgical abortion up to 63 days by vacuum aspiration or dilatation and curettage has been the method of choice since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies. Randomised controlled trials comparing different medical methods (e.g. single drug, combination), ways of application, or different dose regimens, single or combined, for medical abortion, were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant in the first trimester, undergoing medical abortion were the participants. Different medical methods used for first trimester abortion, compared with each other or placebo were included. The outcomes sought include mortality, failure to achieve complete abortion, surgical evacuation (as emergency procedure, non-emergency procedure, or undefined), ongoing pregnancy at follow-up, time until passing of conceptus (> 3-6 hours), blood transfusion, blood loss (measured or clinically relevant drop in haemoglobin), days of bleeding, pain resulting from the procedure (reported by the women or measured by use of analgesics), additional uterotonics used, women's dissatisfaction with the procedure, nausea, vomiting, diarrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously. The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. A form was designed to facilitate the data extraction. Data were processed using Revman software. MAIN RESULTS: Thirty-nine trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. 2) Mifepristone alone is less effective compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Similarly, the 5 trials included in the comparison of prostaglandin compared to the combined regimen reported in all but one higher effectiveness with the combined regime compared to prostaglandin. The results of these studies were not pooled but the RR of failure with prostaglandin alone is between 1.4 to 3.75 and the 95% confidence intervals indicate statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference when using split dose compared to single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin: there was no statistically significant difference in failure to achieve complete abortion comparing methotrexate administered intramuscular to oral (RR 2.04, 95% CI 0.51 to 8.07). Similarly, early (day 3) vs late (day 5) administration of prostaglandin showed no significant of prostaglandin showed no significant difference (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs methotrexate and no statistically significant differences were observed in effectiveness between the groups. REVIEWERS' CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Misoprostol vaginally is more effective than orally. Some of the results are based on small studies only and therefore carry some uncertainty. Almost all trials were conducted in hospital settings with good access to support and emergency services. It is therefore not clear if the results are readily applicable to under-resourced settings where such services are lacking even if the agents used are available.

Medical methods for first trimester abortion.

BACKGROUND: Surgical abortion up to 63 days by vacuum aspiration or dilatation and curettage has been the method of choice since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies. Randomised controlled trials comparing different medical methods (e.g. single drug, combination), ways of application, or different dose regimens, single or combined, for medical abortion, were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant in the first trimester, undergoing medical abortion were the participants. Different medical methods used for first trimester abortion, compared with each other or placebo were included. The outcomes sought include mortality, failure to achieve complete abortion, surgical evacuation (as emergency procedure, non-emergency procedure, or undefined), ongoing pregnancy at follow-up, time until passing of conceptus (> 3-6 hours), blood transfusion, blood loss (measured or clinically relevant drop in haemoglobin), days of bleeding, pain resulting from the procedure (reported by the women or measured by use of analgesics), additional uterotonics used, women's dissatisfaction with the procedure, nausea, vomiting, diarrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously. The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. A form was designed to facilitate the data extraction. Data were processed using Revman software. MAIN RESULTS: Thirty-nine trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. 2) Mifepristone alone is less effective compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Similarly, the 5 trials included in the comparison of prostaglandin compared to the combined regimen reported in all but one higher effectiveness with the combined regime compared to prostaglandin. The results of these studies were not pooled but the RR of failure with prostaglandin alone is between 1.4 to 3.75 and the 95% confidence intervals indicate statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference when using split dose compared to single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin: there was no statistically significant difference in failure to achieve complete abortion comparing methotrexate administered intramuscular to oral (RR 2.04, 95% CI 0.51 to 8.07). Similarly, early (day 3) vs late (day 5) administration of prostaglandin showed no significant of prostaglandin showed no significant difference (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs methotrexate and no statistically significant differences were observed in effectiveness between the groups. REVIEWER'S CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Misoprostol vaginally is more effective than orally. Some of the results are based on small studies only and therefore carry some uncertainty. Almost all trials were conducted in hospital settings with good access to support and emergency services. It is therefore not clear if the results are readily applicable to under-resourced settings where such services are lacking even if the agents used are available.

Misoprostol and illegal abortion in Fortaleza, Brazil.

Misoprostol, a prostaglandin E1 analogue indicated for ulcer treatment, has been widely used as an abortifacient by women in Brazil, where abortion is legal only in cases of rape or incest, or to save the woman's life. Because misoprostol is an inefficient abortifacient, many women who use it have incomplete abortions and need uterine evacuation. We reviewed the records of women admitted to the main obstetric hospital of Fortaleza, capital of Ceará state, Brazil, between January, 1990, and July, 1992, for uterine evacuation after induced abortion. The number of incomplete abortions induced by misoprostol increased substantially during the first half of 1990, and declined thereafter. Of the 593 cases in 1991, 75% were related to misoprostol, 10% to the use of other specified drugs, and 6% to unspecified drugs. For the remaining 9% the procedure used was not recorded; these included 3% in whom abortion had been induced by a clandestine abortionist. The number of uterine evacuations per month fell from 89 in August, 1990, to 62 in July, 1991, when sales of misoprostol in Ceará state were suspended. The fall continued after the sale of misoprostol ceased, to about 20 cases in December, 1991; numbers remained around this level until June, 1992, sustained by clandestine sales. The lack of access to contraception is the main reason for the large numbers of unplanned pregnancies and is a major public health issue for Brazilian women. The prohibition of abortion creates a void in which misuse of medicines is one extra complication, mainly because of the poor control of drug marketing.

Pregnancy and offspring after adjuvant chemotherapy in breast cancer patients.

A retrospective review of 227 consecutive breast cancer patients who were 35 years of age or younger and who had been given doxorubicin-containing adjuvant chemotherapy was conducted to determine the frequency of pregnancy and its effect on the clinical course of the disease. Also, the status of the newborn was evaluated. There were 33 pregnancies in 25 patients (10 pregnancies were terminated, 2 patients had spontaneous abortions, and 19 patients gave birth to full-term offspring without fetal malformation). Two patients were still pregnant at the time of this report. The median interval between the completion of chemotherapy and pregnancy was 12 months. Eight patients who became pregnant experienced temporary amenorrhea during chemotherapy. Of the 25 patients who became pregnant, recurrent disease subsequently developed in 7 and 3 died. A patient's disease-free and overall survival status was not adversely effected by pregnancy. These data illustrate that in a sizeable fraction of patients 35 years of age or younger treated with adjuvant doxorubicin-containing therapy, ovarian function remained intact and subsequent pregnancy did not affect the disease-free or overall survival of the patients.

Spermicidal contraceptives and poor reproductive outcomes: the epidemiologic evidence against an association.

The first widely publicized report of an association between spermicidal contraception and congenital malformations and spontaneous abortion had considerable impact on obstetric practice. A large number of more recent epidemiologic studies have generally failed to support the earlier finding, and it is concluded that no such association has been demonstrated. The available evidence precludes the need for additional regulation of spermicidal contraception.

PIP: This article reviews the 14 known epidemiologic studies that have considered an association of spermicide use with congenital malformations, spontaneous abortions, or low birth weight, and presents some observations on how epidemiologic inquiry relates to regulatory policy. 5 case control studies and 5 prospective studies examined congenital malformations. Some studies examined selected congenital diagnoses whereas others reported for all malformations. The 1 case-control study reporting a positive association had only 16 cases and represented a select group of newborn infants with Down's syndrome and congenital heart defects. The time of exposure was simply "during the period before this pregnancy". The only prospective study reporting an association can be criticized for the extremely broad measure of spermicide use (a prescription filled within 600 days of delivery), the low number of malformations observed, the lack of a common etiology in the assemblage of malformations identified as being associated with spermicides, and inadequate control for confounding variables. Of the 4 prospective studies examining associations of spermicides and risk of miscarriage, 1 that found a positive association failed to adjust for potentially confounding factors. A reported association between spermicide use and spontaneous abortion identified in a recent analysis of the National Survey of Family Growth data suffered from several major difficulties including comparing women exposed to spermicides close to conception with those exposed after conception; asking women about their pregnancies over a period of almost 4 years, enhancing the chance of biased recall; and using a fixed observation period so that women with a history of multicple spontaneous abortions were likely to be overrepresented. A better-designed cohort study with 32,123 cases found no association between spermicide use and spontaneous abortion. 2 research groups that studied low birth weight and spermicide use found that the proportion of clinically low birth weight infants was not significantly influenced by spermicide usage, or found no association at all. It is quite common in epidemiology for the 1st published study of an association to suggest a particular association, and it is probably no coincidence that the 1st and most widely publicized spermicide study was a positive one. A number of large studies specifically designed to test the spermicide malformation hypothesis are currently in the data collection stage. The risks and benefits of a product itself and the risks and benefits of regulation both need to be considered for regulatory purposes. Regarding the decision on whether to label spermicide contraceptives as a potential hazard, the products have social benefits and the epidemiological evidence for an association with poor reproductive outcome is very weak.

Fertility after discontinuation of oral contraceptives.

Concern has been expressed regarding fertility following oral contraceptive (Pill) use. A review of the literature indicates that there is a slight delay in the return of fertility in Pill users but no permanent impairment results. A small proportion of women experience a prolonged period of amenorrhoea following cessation of combined oral contraception, but whether the Pill plays an aetiological role is doubtful since there appear to be no differences in endocrine profiles amongst women with amenorrhoea following Pill use and those with secondary amenorrhoea who have never used oral contraceptives. Factors which may predispose to amenorrhoea following Pill use are: late onset of menarche, previous oligomenorrhoea and low body weight. Following adequate investigation and treatment, fertility rates in women with the so-called post-Pill amenorrhoea syndrome return to normal. There is no evidence of any delay in the return of fertility in women who use the progestogen-only Pill.

PIP: Concern has been expressed regarding fertility following oral contraceptive (OC) use. A review of the literature indicates that there is a slight delay in the return to fertility in pill users but no permanent impairment results. A small proportion of women experience a prolonged period of amenorrhea following cessation of combined OCs but whether the pill plays an etiological role is doubtful since there appear to be no differences in endocrine profiles among women with amenorrhea following OC use and those with secondary amenorrhea who have never used OCs. Factors which may predispose to amenorrhea following OC use are: late onset of menarche, previous oligomenorrhea, and low body weight. Following adequate investigation and treatment, fertility rates in women with so-called postpill amenorrhea syndrome return to normal. There is no evidence of any delay in the return to fertility in women who use the progestogen-only pill.

Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings.

The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of 3 separate control groups. The controls consisted of 167 age-matched, normal women, 20 siblings not exposed to DES who had achieved pregnancy, and their mothers. Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls. The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001). When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001). The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).

Extraamniotic intermittent administration of prostaglandin F2 alpha during the first and second trimesters of pregnancy.

Extraamniotic application of prostaglandin F2 alpha (PGF2 alpha) was used for legal abortion in the series of 1012 women. The pregnancies were terminated by abortion between the 6th and 27th weeks of pregnancy. In 86.7% of the cases, intermittent extraamniotic application of PGF2 alpha led to complete or incomplete abortions. Of the 26 failures, nine were caused by technical difficulties. In 17 primigravidae, the cervical canal remained closed. There were no statistically related differences between the different weeks of the pregnancy with regard to success and failure rates. The mean PGF2 alpha dose and abortion time increased significantly (p less than 0.01) with increasing duration of pregnancy. 80% of the patients suffered from undesirable side effects. The morbidity rate for the period up to six weeks following the abortion was 3.2%.