Mifepristone–Misoprostol Versus Misoprostol Alone for Early Missed Miscarriage After ART and Spontaneously Conceived Pregnancies

Background: Missed miscarriage (MM) is a common first-trimester complication. Misoprostol alone achieves moderate success, while combination therapy with mifepristone improves outcomes in spontaneous pregnancies. Evidence in assisted reproductive technology (ART) pregnancies is scarce. We evaluated whether combined mifepristone–misoprostol improves outcomes in ART pregnancies compared with misoprostol alone and compared results with spontaneously conceived (SC) pregnancies. Methods: This retrospective matched cohort study was conducted at a single center (2017–2024). ART pregnancies were matched 1:2 with SC pregnancies by maternal age. Patients received misoprostol alone or 200 mg mifepristone followed 48 h later by misoprostol. The primary outcome was treatment success, defined as complete uterine evacuation without repeat misoprostol or surgery. Secondary outcomes included emergency visits, surgical procedures, and ART-related predictors. Subgroup analyses were performed by ART protocol. Results: Among 307 patients (94 ART, 213 SC), combined therapy yielded higher success than misoprostol alone in SC (84% vs. 71%, p = 0.023) and ART pregnancies (95% vs. 80%, p = 0.035). In hormonally supported frozen embryo transfer (HRT-FET) cycles, success was 100% with combined therapy versus 80% with misoprostol alone. Conclusions: Combined mifepristone–misoprostol is more effective than misoprostol alone, with particularly high success in HRT-FET cycles.