Letrozole before misoprostol versus misoprostol for termination of first trimester missed miscarriage: a randomized controlled clinical trial

Background Missed miscarriage is a common obstetric problem that requires effective management to ensure complete uterine evacuation. Misoprostol is widely used, but its success rate varies, and some cases need surgical intervention. Letrozole, an aromatase inhibitor, may improve the endometrial response to prostaglandins, and enhance misoprostol efficacy. Aim To compare the effectiveness of letrozole pretreatment followed by misoprostol versus misoprostol alone in the medical management of first-trimester missed miscarriage. Patients and methods A randomized controlled clinical trial was conducted on 90 women with first-trimester missed miscarriage at Tanta University Hospitals between October 2023 and September 2024. The participants were randomized to either the misoprostol-only group or the letrozole–misoprostol group. The rate of total uterine evacuation without surgical intervention was the main result. Secondary outcomes included onset and duration of bleeding, need for curettage, side effects, and patient tolerance. Results Women who received letrozole followed by misoprostol achieved significantly higher rates of complete evacuation compared with the misoprostol-only group (73.3 vs. 37.8%, P <0.001). The induction-to-abortion interval and bleeding duration were also shorter in the combination group. However, nausea, vomiting, abdominal cramps, and hot flushes occurred more frequently among women who received the combined regimen. Conclusion Pretreatment with letrozole enhances the efficacy of misoprostol in first-trimester missed miscarriage, leading to faster and more successful medical termination while reducing the need for surgical intervention. To validate these results and improve treatment regimens, larger multicenter trials are advised.