Elsevier

Contraception

Volume 87, Issue 1, January 2013, Pages 26-37
Contraception

Review article
First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review

https://doi.org/10.1016/j.contraception.2012.06.011Get rights and content

Abstract

Background

The dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure.

Study Design

To identify eligible reports, we searched Medline, reviewed reference lists of published reports, and contacted experts to identify all prospective trials of any design of medical abortion using 200 mg mifepristone followed by misoprostol in women with viable pregnancies up to 63 days' gestation. Two authors independently extracted data from each study. We used logistic regression models to explore associations between 15 characteristics of the trial groups and, separately, the rates of medical abortion failure and of ongoing pregnancy.

Results

We identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age > 8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions.

Conclusions

Early medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe.

Introduction

Since mifepristone was introduced in France and China more than two decades ago, medical abortion with this antiprogestin has expanded rapidly throughout the world. Mifepristone is now registered in 50 countries (www.gynuity.org, accessed 14 December 2011). In the United States, about one fifth of all outpatient abortions are performed medically [1], and in several countries in Europe, the proportion exceeds 60% [2], [3].

Although medical abortion regimens approved by most government regulatory agencies specify 600 mg mifepristone, in practice, a dose of 200 mg is standard worldwide [4], [5], [6], [7]. A prostaglandin, misoprostol, is administered after the mifepristone to enhance success. The dose, route, and timing of administration of misoprostol are not standardized. In the United States, affiliates of Planned Parenthood Federation of America provide 800 mcg buccally 24–48 h after the mifepristone [4]. The International Federation of Obstetricians and Gynaecologists recommends either vaginal, buccal, or sublingual administration [5] as do the World Health Organization [6] and the United Kingdom Royal College of Obstetricians and Gynaecologists [7], which also recommend oral dosing at gestational ages up to 49 days. Lower doses, divided doses, oral administration, and a shorter or longer interval between the two drugs also have been used clinically or evaluated in research studies.

The purpose of this review is to summarize published data on the effectiveness and safety of regimens including 200 mg mifepristone followed by misoprostol for early medical abortion. We also explore whether variation among studies in the frequency of medical abortion failure could be explained by characteristics of the study designs, treatment protocols, or study populations.

Section snippets

Materials and methods

We searched Medline using PubMed on 7 July 2011 for studies of medical abortion using mifepristone and misoprostol. Our search strategy was as follows: (abortion OR pregnancy termination OR termination of pregnancy) AND (mifepristone OR RU 486 OR RU-486 OR RU486 OR Mifegyne OR Mifeprex OR Medabon) AND (misoprostol OR prostaglandin). In addition, we reviewed the reference lists of relevant articles, and we contacted experts in the field for information about any published or unpublished trials

Results

The Medline search yielded 860 citations. Of these, 81 included at least one group of women who were treated with an abortion regimen that used 200 mg mifepristone followed by misoprostol in viable first trimester pregnancy [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53],

Discussion

Medical abortion using mifepristone 200 mg followed by misoprostol in the first 63 days of gestation is remarkably effective and safe. In trials that together included more than 45,000 women conducted in disparate settings over nearly two decades using a variety of regimens and treatment protocols, fewer than 5% of subjects required surgery to complete termination of the pregnancy. The proportion who had ongoing pregnancy at follow-up — the outcome of greatest concern to clinicians — was 1.1%.

Acknowledgments

Financial support for this review was provided by an anonymous charitable foundation.

Reprints will not be available.

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    E.G.R. and C.S. conducted literature searches and abstracted data. M.A.W. performed statistical analyses. All authors contributed equally to interpretation and manuscript preparation. No authors have any conflicts of interest.

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