Clinical Question

In women with early pregnancy loss, does pretreatment with mifepristone (Mifeprex) before misoprostol (Cytotec) improve outcomes over treatment with misoprostol alone?

Bottom Line

In women with early pregnancy loss between five and 12 weeks' gestation, pretreatment with 200 mcg of oral mifepristone before 800 mcg of vaginal misoprostol increases the likelihood of successful expulsion of the gestational sac (number needed to treat [NNT] = 6). (Level of Evidence = 1b–)

Synopsis

The researchers recruited adult women who had a closed cervical os and an ultrasound that showed a nonviable intrauterine pregnancy between five and 12 weeks' gestation. They excluded women with an open cervical os or no visible gestational sac, anemia, a viable or ectopic pregnancy, or any contraindication to the study medications. The mean age of the 300 participants was 30 years, 44% were black, and most had a six- to eight-week gestation. Women were randomized to receive directly observed therapy with oral mifepristone, 200 mcg, followed by 800 mcg of misoprostol (four tablets) inserted vaginally 24 hours later, or to the misoprostol alone. Although women and their physicians were not masked to the treatment assigned, the person assessing the ultrasound was masked. Each woman had a follow-up visit at one to four days, and if a gestational sac was present on the ultrasound, she was offered a second dose of misoprostol or the option of surgical evacuation, with follow-up approximately one week after that. All women had a final follow-up visit at one month. Only seven women were lost to follow-up or withdrew consent in each group. The likelihood of expulsion at the initial follow-up visit was significantly higher with the combination therapy (84% vs. 67%; 95% confidence interval for the difference, 7% to 26%; NNT = 6). Women who did not follow instructions and took the misoprostol fewer than 18 hours after the mifepristone had a somewhat lower likelihood of success (80% vs. 87%; P = .22). Among women who had up to two doses of misoprostol, gestational sac expulsion at 30 days was also significantly more likely in the combination therapy group (91% vs. 76%; NNT = 7). Women receiving pretreatment with mifepristone were significantly more likely to experience vomiting (27% vs. 15%; number needed to treat to harm [NNTH] = 8) and headache (59% vs. 48%; NNTH = 9).

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Concealed

Setting: Various (meta-analysis)

Reference: SchreiberCACreininMDAtrioJSonalkarSRatcliffeSJBarnhartKTMifepristone pretreatment for the medical management of early pregnancy loss. N Engl J Med2018;378(23):2161–2170.