Efficacy and Safety of Letrozole, Misoprostol and Their Combination in First Trimester Missed Miscarriage: A randomised clinical trial

Objectives: This study evaluated the efficacy and safety of misoprostol, letrozole and their combination in first trimester missed miscarriage. Methods: This single-blind, randomised controlled trial was conducted between March 2023 and August 2024 among women diagnosed with first trimester missed miscarriage at Kasr Al-Aini Hospital, Cairo, Egypt. Participants were randomly assigned to three groups: misoprostol-only (Group A), letrozole plus misoprostol (Group B) and letrozole-only (Group C). The primary outcome was the rate of complete miscarriage. Secondary outcomes included abortion timing, adverse effects, need for surgical evacuation and the effect of age, body mass index (BMI) and gestational age on success. Results: = 0.0005). Early abortion (by day 4) occurred in 68.4% (group B), 46.5% (group A) and 37.5% (group C). Group B also had the highest incidence of adverse effects, particularly bleeding (85.3%) and pain (92.0%), although severe events were rare. Letrozole-only (group C) had the fewest side effects (26.7%) and required no surgical evacuations. Combination therapy proved most effective across subgroups by age, BMI and gestational age. Conclusion: Combining letrozole with misoprostol significantly improves complete miscarriage rates with tolerable safety. Letrozole alone is safer but less effective. Thus, combination therapy may offer an optimal non-surgical strategy for individualised management.