The use of letrozole or mifepristone for pre‐treatment of medical termination of pregnancy: A randomized, non‐inferiority trial

OBJECTIVE: Mifepristone improves the effectiveness of medical termination of pregnancy (mTOP) but is expensive and restricted in some settings. Letrozole has been proposed as a potential alternative. This study aimed to evaluate whether letrozole is non-inferior to mifepristone as a pre-treatment for mTOP. METHODS: We conducted an assessor-blinded, randomized controlled non-inferiority trial comparing mifepristone versus letrozole pre-treatment for mTOP. Participants were randomized to one of two groups: the control group received oral mifepristone 200 mg on Day 1, while the intervention group received oral letrozole 10 mg daily from Day 1 to Day 3. On Day 3, both groups received per-vaginal misoprostol 800 mcg, followed by an additional 400 mcg after 4 h if there were no signs of abortion. Follow-up was conducted by Day 28 post-mTOP. The primary outcome was complete abortion, defined as a negative urine pregnancy test with no ongoing vaginal bleeding and no need for surgical evacuation by Day 28. Data was analyzed using SPSS Version 30.0. RESULTS: The intention-to-treat analysis included 135 participants, with a mean gestational age of 8.2 weeks. Complete abortion occurred in 72.1% (49/68) of the letrozole group compared with 85.1% (57/67) of the mifepristone group, with an absolute risk difference of -13.0% (95% CI -26.4 to +0.9). The lower bound of the 95% CI crossed the prespecified non-inferiority margin of -15%, so non-inferiority was not demonstrated. CONCLUSION: Letrozole could not be shown to be a non-inferior alternative to mifepristone as pre-treatment for mTOP. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (ID: NCT05341817) on April 5, 2022, and received ethics board approval from the SingHealth Centralized Institutional Review Board (CIRB 202110-00035).