Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial

Abstract

Objective: To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage. Design: Prospective open-label non-inferiority randomised controlled trial. Setting: A university-affiliated hospital. Population: We recruited 294 women diagnosed with first-trimester missed miscarriage who opted for medical treatment. Methods: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24–48 h later by 800 μg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once-a-day for 3 days, followed by 800 μg misoprostol vaginally on the third (i.e. last) day of letrozole administration. Main outcome measures: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post-treatment. Secondary outcomes included induction-to-expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. Results: The complete evacuation rates were 97.8% (95% CI 95.1%–100%) and 97.2% (95% CI 94.4%–99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non-inferiority). The mean induction-to-tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post-treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. Conclusions: Letrozole is non-inferior to mifepristone as a pre-treatment, followed by misoprostol, for the medical treatment of first-trimester missed miscarriage.