In a randomized trial of women with early pregnancy loss, pretreatment with mifepristone before misoprostol was superior to misoprostol alone at achieving gestational sac expulsion by the time of the first follow-up visit without additional intervention.
“Women generally prefer active management; the ability to have control over the management of miscarriage may relieve some of the emotional burden that accompanies first trimester pregnancy loss,” Courtney A. Schreiber, MD, of the University of Pennsylvania, Philadelphia, and her coauthors wrote in the New England Journal of Medicine. But misoprostol (Cytotec) alone for women with a closed cervical os can require a second dose or intervention.
The trial enrolled 300 participants. Each had an ultrasound showing a nonviable intrauterine pregnancy of 5-12 weeks’ gestation. Women with an incomplete or inevitable abortion (that is, the absence of a gestational sac, an open cervical os, or both) were excluded, as misoprostol alone is effective for management of that diagnosis.
After randomization, 149 participants received 200 mg of oral mifepristone (Mifeprex), with 800 mcg misoprostol administered approximately 24 hours later. The other 151 participants received the standard 800 mcg dose of misoprostol alone. In both groups, the misoprostol was self-administered vaginally at home by inserting four 200-mcg tablets.
Follow-up came 24 hours to 4 days after misoprostol administration. The primary outcome was a gestational sac expulsion by the time of this follow-up, and no additional surgical or medical intervention within 30 days. If the gestational sac was present at follow-up, participants chose either expectant management, surgical management, or a second misoprostol dose.
The primary outcome was achieved in 124 of 148 women (83.8%; 95% confidence interval, 76.8-89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0-74.6) in the misoprostol-alone group for a relative risk of 1.25 (95% CI, 1.09 to 1.43). Two women were lost to follow-up and one who was declared ineligible because of a possible ectopic pregnancy.
At 30 days’ follow-up, the cumulative rate of gestational sac expulsion with up to two doses of misoprostol was 91.2% (95% CI, 85.4-95.2) in the mifepristone-pretreatment group and 75.8% (95% CI, 68.2%-82.5%) in the misoprostol-alone group. Also by 30 days’ follow-up, 13 women in the mifepristone-pretreatment group and 35 women in the misoprostol-alone group had undergone uterine aspiration (relative risk, 0.37; 95% CI, 0.21-0.68).