Original research articleComparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone☆
Introduction
Nonsurgical abortion methods using the drugs mifepristone and misoprostol have the potential to improve abortion care. Medical methods have several advantages over surgical evacuation, particularly for use in low-resource settings, including reducing the need for surgery, sterilization of instruments, specific clinic rooms and surgically trained personnel. In countries where demand for abortion has overwhelmed surgical abortion services or where access to surgical services may be restricted to higher level facilities, medical abortion could reduce the workload for providers and facilities currently providing surgical abortion care. Widespread adoption of mifepristone medical abortion has been limited due to lack of access to the drug and its perceived high cost in many low-resource countries [1]. Misoprostol, on the other hand, is widely available and inexpensive, and has therefore been promoted as an alternative to the combined regimens. In recent years, a host of new mifepristone and misoprostol products have become available which has reduced the cost of both drugs and facilitated access to medical abortion methods [2], [3]. The mifepristone pill continues to cost considerably more than the misoprostol pill and alone represents the most significant portion of the cost of any medical abortion regimen.
Mifepristone and misoprostol have been used by millions of women for early pregnancy termination. Several refinements from the original protocol [4] have reduced the dose of mifepristone [5], [6], [7], introduced home use of misoprostol [1], [4], [5], shortened the time between mifepristone and misoprostol administration [8], [9], [10], [11], and tested alternative doses and routes of misoprostol [5], [12], [13], [14], [15]. Providers have come increasingly interested in regimens using buccal misoprostol after mifepristone for medical abortion. Results from the large randomized trial in the United States comparing misoprostol 800 mcg given orally or buccally 24 to 36 h after 200 mg mifepristone through 63 days since the last menstrual period (LMP) showed 96.2% efficacy with buccal misoprostol (vs. 91.3% with oral) [12]. These results contributed to a policy change in the United States in favor of the 200 mg mifepristone+800 mcg buccal misoprostol as standard care for early abortions through 63 days LMP at Planned Parenthood affiliate clinics [16].
Misoprostol-alone has been used to induce abortions for over a decade. Its first use for this indication was documented in Brazil in the early 1990s, where women learned of the drug's abortifacient properties and began to use it clandestinely. Dozens of studies have examined various misoprostol regimens in an effort to determine the best regimen for this indication [14]. The most widely used regimen in studies includes repeated 800 mcg vaginal doses over a period of hours or days until a complete abortion is achieved. Research testing vaginal administration of misoprostol-alone for abortions up to 63 days LMP has reported success rates ranging from 66% to 90% [14], [17], [18], [19], [20], [21], [22], [23]. Oral routes of misoprostol administration have proven less effective [18]. The largest randomized controlled trial examined two vaginal and sublingual misoprostol regimens composed of 800 mcg misoprostol administered at either 3- or 12-h intervals, resulting in a four-arm trial [22]. Dosing interval had a more important effect with the sublingual route: women given 800 mcg sublingual misoprostol at 3-h intervals had 84% efficacy vs. 78% efficacy with 12-h intervals, while 800 mcg vaginal misoprostol worked similarly regardless of dosing interval: 85% efficacy at 3 h vs. 83% at 12 h. Ongoing pregnancy rates ranged from 4% to 9% across study arms. A trial by Jain et al. [23] randomized women to either 200 mg mifepristone followed 24 h later by 800 mcg vaginal misoprostol or repeated doses (three maximum) of 800 mcg vaginal misoprostol in gestations through 56 days LMP and reported 95.7% efficacy with mifepristone+vaginal misoprostol vs. 88% with vaginal misoprostol-alone.
Although there is limited information on buccal misoprostol for medical abortion, the route appears promising given the pharmacokinetic evidence. The pharmacokinetic profile of buccal and vaginal misoprostol is similar, suggesting that the buccal route might work similarly to the vaginal route when administered alone for early medical abortion [24], [25]. Previous research has documented regular and sustained uterine contractility with both routes [26].
Abortion has been legal in Vietnam since 1965 and widely available since the 1980s [27]. In 2002, mifepristone medical abortion was approved by the Ministry of Health and included in the National Reproductive Health Standards and Guidelines. For now, the method is only offered to women with gestations through 56 days LMP at tertiary level facilities, although there are plans to broaden access to other levels of the health care system in the future.
This double-blinded RCT compares two regimens for early medical abortion, one with and one without mifepristone to determine whether a misoprostol-alone regimen has a comparable safety, efficacy and acceptability profile to a combined regimen.
Section snippets
Methods
From August 2007 through March 2008, 400 women presenting for early medical abortion with gestational ages up to 63 days by LMP and living or working within an hour from the hospital were determined eligible to participate in the study and recruited at a large tertiary facility in Ho Chi Minh City, Vietnam. Gestational age was determined primarily by clinical examination and transvaginal ultrasound. Additional inclusion criteria were intrauterine pregnancy, general good health, able to provide
Participant characteristics and treatment group
Table 1 details participants' baseline characteristics. Four hundred women were enrolled and assigned to either misoprostol-only (n=198) or mifepristone+misoprostol (n=202). Participants averaged 28 and 29 years of age in the misoprostol-alone and mifepristone+misoprostol arms, respectively, with the majority reporting having completed secondary level education; 80% were married. This was the first pregnancy for approximately a quarter of participants. This trial is reported according to the
Discussion
This study explored two regimens for early medical abortion, one with mifepristone+misoprostol and another with misoprostol-alone. Both regimens are widely used in a range of settings, with the combined mifepristone+misoprostol regimen having been used by millions of women worldwide. Use of misoprostol-alone has been advocated in the absence of mifepristone availability in many regions, particularly sub-Saharan Africa and Latin America. Yet, the results from the present trial clearly document
Acknowledgments
We thank the women who participated in this trial and the providers who provided their care and carefully recorded data throughout the recruitment process.
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This study was funded by an anonymous donor.