Effectiveness, safety and acceptability of mifepristone compared with other interventions in reproductive-age women using emergency contraception for the prevention of pregnancy: a systematic review and meta-analysis.

BACKGROUND: Emergency contraception (EC) prevents pregnancy after unprotected sexual intercourse using oral medications or intrauterine devices. Comparative evidence on effectiveness and safety is essential to inform emergency contraceptive counselling. OBJECTIVES: To evaluate the effectiveness, safety and acceptability of mifepristone compared with other EC methods among reproductive-age women. METHODS: We searched CENTRAL, MEDLINE, Embase, Global Index Medicus, Scopus conference abstracts, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform through 28 February 2025. Randomised controlled trials enrolling women within 5 days of unprotected sexual intercourse and comparing mifepristone with oral EC methods (levonorgestrel (LNG), Yuzpe regimen, ulipristal acetate) or intrauterine devices (IUDs) (copper or LNG) were included. Pregnancy was the primary outcome. Risk of bias was assessed using the Risk of Bias 1 (RoB 1) tool. Meta-analyses used fixed or random-effects models and certainty of evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Eighty-seven trials including approximately 36 000 participants were analysed. Mifepristone reduced pregnancy risk compared with the Yuzpe regimen (risk ratio (RR) 0.14, 95% CI 0.05 to 0.41; moderate-certainty evidence). It was more effective compared with LNG with either low-dose (<25 mg; RR 0.73, 95% CI 0.59 to 0.90; high-certainty) or mid-dose (25-50 mg; RR 0.67, 95% CI 0.49 to 0.91; moderate-certainty) levels. Evidence was inconclusive regarding comparisons with the copper IUD. Mifepristone causes less nausea and vomiting than Yuzpe. Mifepristone increases the risk of delayed menses relative to both Yuzpe and LNG. CONCLUSIONS: Mifepristone is an effective emergency contraceptive, potentially more effective than commonly used oral EC methods, with a favourable side effect profile aside from delayed menstruation.