Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone, according to a study published in The New England Journal of Medicine. First-trimester miscarriage is the most common pregnancy complication in the United States, and while misoprostol treatment is recommended by society guidelines, the standard dose of 800 µg has low efficacy in women with a closed cervical os. Mifepristone is a 19-nor steroid that acts as a competitive progesterone-receptor antagonist and glucocorticoid-receptor antagonist and helps prepare the myometrium and cervix for prostaglandin activity.
The study included 300 women with an anembryonic gestation or embryonic or fetal death who were randomized to either pretreatment with 200 mg of oral mifepristone, followed by 800 µg of vaginal misoprostol (pretreatment group) or 800 µg of vaginal misoprostol alone (misoprostol-alone group). Participants were eligible if they were at least 18 years old and had an ultrasound that showed a nonviable intrauterine pregnancy between 5 and 12 completed weeks’ gestation. Women were excluded if they had an incomplete or inevitable abortion, a contraindication to misoprostol or mifepristone, evidence of a viable or ectopic pregnancy, a hemoglobin level lower than 9.5 g/dL, a known clotting defect, or a pregnancy with an intrauterine device in place.
The primary outcome of the study was successful gestational sac expulsion by the first follow-up visit (at least 24 hours but not more than 4 days after misoprostol use) with one dose of misoprostol and no additional surgical or medical interventions within 30 days. Secondary outcomes included adverse events (AEs) measured by a Likert scale, acceptability of treatment based on responses to a 3-point Likert scale, and assessment of the clinical characteristics associated with gestational sac expulsion.
The misoprostol-alone group consisted of 151 randomly assigned women, while 149 women were assigned to the mifepristone-pretreatment group. During the study, three women were excluded from the results (2 lost to follow-up and 1 found to be clinically ineligible). The median number of days between misoprostol administration and first follow-up was 2.0 (range, 0.5-5.5) in the mifepristone-pretreatment group and 2.6 (range, 0.7-9.6) in the misoprostol-alone group (P = 0.04). In the mifepristone group, 124 of 148 women (83.8%; 95% CI, 76.8-89.3) had treatment success by the first follow-up visit with no further interventions necessary 30 days after treatment. In the misoprostol-alone group, 100 of 149 women (67.1%; 95% CI, 59.0-74.6) had treatment success. In the pretreatment group, 65 women did not wait the full 24 hours before administering misoprostol. In these women, the success rate was 79.7%.
In the pretreatment group, 24 women (16.2%) did not experience gestational sac expulsion by the first 24-hour follow-up and in the misoprostol-alone group, 49 women (32.9%) did not have expulsion. Among these 73 women, 41% chose expectant management, 27% chose a second dose of misoprostol, and 31% underwent uterine aspiration. Complete expulsion of the gestational sac with one dose of misoprostol by Day 8 occurred in 130 of 149 women. Thirty days after treatment, 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 pretreatment group and 75.8% (95% CI, 68.2-82.5) in the misoprostol-alone group.
Through subgroup analyses, the researchers found that rates of treatment success by the first follow-up visit among women who were at 9 weeks’ gestation or less were 84.8% (117 of 138 women) in the pretreatment group and 66.7% (94 of 141 women) in the misoprostol-alone group. There were also no reported significant AEs either arm of the study.
A few strengths and limitations were noted by the authors. Among the strengths mentioned were the high retention rate of the participants and the diverse population of participants. Among the limitations mentioned was the vaginal administration of misoprostol. In future studies, the authors suggested, might want be warranted to explore success rates with oral, rectal, buccal, or sublingual routes. They also noted that several participants in the pretreatment group did not wait the full 24 hours between mifepristone pretreatment and misoprostol, so the effect on treatment of shorter intervals between administration mifepristone and misoprostol might be another avenue for exploration.