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

## TL;DR

This study found that combining letrozole and misoprostol is more effective for managing first trimester missed miscarriage than using either drug alone.

## Contribution

The study introduces combination therapy of letrozole and misoprostol as a novel non-surgical approach for first trimester missed miscarriage.

## Key findings

- Combination therapy (letrozole + misoprostol) had the highest complete miscarriage rate (76.0%) by day 7.
- Letrozole-only had the fewest side effects and no surgical evacuations needed.
- Combination therapy showed effectiveness across subgroups of age, BMI, and gestational age.

## Abstract

This study evaluated the efficacy and safety of misoprostol, letrozole and their combination in first trimester missed miscarriage.

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.

A total of 225 women were included in this study. Group B had the highest cumulative complete miscarriage rate by day 7 (76.0%) compared with Group A (53.5%) and Group C (62.5%) (P = 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.

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.