Efficacy and safety of emergency contraception interventions: a systematic review and Bayesian network meta-analysis.

Abstract

Objective: To assess the efficacy and safety of emergency contraception (EC) interventions.

Methods: Literature published until 28 December 2024 was retrieved from nine databases. Randomised controlled trials (RCTs) evaluating the efficacy of copper or levonorgestrel intrauterine devices (Cu-IUDs or LNG-IUDs), oral levonorgestrel (LNG), mifepristone (MFP), ulipristal acetate (UPA) and oral EC plus cyclooxygenase inhibitor (COX) were considered eligible. A Bayesian network meta-analysis was conducted to evaluate the relative risk (RR) with a 95% credible interval (CrI) for efficacy and adverse events. Evidence certainty was graded using the CINeMA GRADE application. Pairwise meta-analyses, robustness analyses and Bayesian meta-regressions were conducted to verify the reliability of the results.

Results: Of 17 244 studies, 92 involving 37 260 women were included. With robustness verified, the Cu-IUD was the most effective EC treatment. No significant differences in EC efficacy were observed between LNG-IUD and all other treatments, but with low- or very-low-certainty evidence. With acceptable adverse events, co-treatment with LNG and COX (LNG-COX) was more efficacious than single-dose (RR=0.112, 95%CrI: 0.005, 0.686) or double-dose LNG (RR=0.095, 95%CrI: 0.004, 0.605) with high certainty. MFP (25 mg) and UPA had comparable EC efficacy (RR=0.782, 95%CrI: 0.425, 1.433), whereas MFP tended to induce advancement of the subsequent menstrual period.

Conclusions: Although the efficacy of LNG-COX was confirmed by high-certainty evidence, large-scale validation trials are required before it can be recommended clinically. Owing to within-study bias and imprecision, large RCTs are strongly recommended to assess the efficacy of ECs for interventions without direct comparisons.

Trial registration number: CRD42024627671.