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Am Fam Physician. 2023;107(1):24-25

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Clinical Question

What are the effectiveness, safety, and adverse effects of different medical methods for first-trimester abortion?

Evidence-Based Answer

There is moderate-quality evidence that a combined regimen of mifepristone and misoprostol is more effective than misoprostol alone for medication abortions before 12 weeks of gestation. (Strength of Recommendation [SOR]: B, inconsistent or limited-quality patient-oriented evidence.) The effectiveness of this regimen is no different with a mifepristone dose of 200 mg compared with 600 mg. (SOR: B, inconsistent or limited-quality patient-oriented evidence.) Vaginal administration of misoprostol is more effective than oral administration. (SOR: B, inconsistent or limited-quality patient-oriented evidence.) Adverse effects are typically self-limited and commonly include nausea, vomiting, and diarrhea. Major complications are rare.1

Practice Pointers

In the United States, 20% of pregnancies, excluding miscarriages, end in abortion,2 and more than one-half of abortions provided by U.S. facilities use medication rather than surgery.3 Many regimens have been used worldwide for medication abortion, most commonly prostaglandins, mifepristone, or a combination. Within these regimens, widely varying dosages, timing, and routes of administration have been used. The objective of this Cochrane review was to compare the effectiveness and adverse effects of different regimens.

The Cochrane review included 99 randomized trials examining patients 18 years and older undergoing medication abortion in the first trimester. Most studies were conducted in high-income countries where patients had access to medical follow-up. Because of the many combinations of medication regimens, the studies were grouped to evaluate 24 different comparisons via meta-analysis. The main outcome measured was the failure to achieve complete abortion within two weeks of a medication abortion. Overall, there was a low rate of major complications; the need for blood transfusion was the most severe complication and occurred less than 1% of the time.

Combination regimens were more effective than misoprostol alone (relative risk [RR] = 2.39; 95% CI, 1.89 to 3.02), regardless of the route of misoprostol administration. Combination regimens included misoprostol combined with mifepristone, letrozole, estradiol, tamoxifen, or methotrexate. In patients treated with the combined regimen of misoprostol and mifepristone, no significant differences were noted between 600-mg and 200-mg doses of mifepristone (RR = 1.07; 95% CI, 0.87 to 1.33). Significantly lower failure rates occurred in patients who received 800 mcg of misoprostol compared with 400 mcg (RR = 0.63; 95% CI, 0.51 to 0.78) after treatment with mifepristone. Because studies are limited, no definitive conclusions could be drawn regarding alternative regimens, such as those using methotrexate or tamoxifen combined with prostaglandins.

There was variability among trials in the timing of the misoprostol dose after mifepristone administration. In patients treated with misoprostol one day after receiving mifepristone, complete abortion was less likely to fail vs. patients who took misoprostol six hours after mifepristone (RR = 0.65; 95% CI, 0.46 to 0.91). Overall failure rates were similar in all estimated gestational ages when comparing administration of misoprostol one day after mifepristone vs. two days after mifepristone. In pregnancies with an estimated gestational age of more than 49 days, failure rates were higher when misoprostol was administered on day 2 compared with day 1 (RR = 1.57; 95% CI, 1.09 to 2.27). When comparing routes of administration of misoprostol in combination with mifepristone, the vaginal route was significantly more effective than the oral route (RR = 2.38; 95% CI, 1.46 to 3.87). Sublingual misoprostol was more effective than oral misoprostol (RR = 0.26; 95% CI, 0.10 to 0.68). Patients treated with vaginal medication were less likely to experience gastrointestinal adverse effects than those treated with oral, buccal, and sublingual medication, although this trend was not statistically significant.

Practice guidelines from the American College of Obstetricians and Gynecologists, Society of Family Planning, and National Abortion Federation recommend first-trimester medication abortions as a safe and effective method of ending an undesired pregnancy.4,5 These guidelines support the use of 200-mg mifepristone, when available, and mifepristone combined with misoprostol over a regimen of misoprostol alone. The American College of Obstetricians and Gynecologists recommends against oral administration of misoprostol because of possible lower effectiveness.4 Most trials in the Cochrane review required confirmation of intrauterine pregnancy by ultrasonography, availability of emergency back-up facilities, and close medical follow-up, which may limit the applicability of these findings to resource-poor settings or in patients pursuing self-managed abortions.

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These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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