For the millions of women worldwide who face unintended pregnancy risk after unprotected intercourse, the relative performance of available emergency contraception (EC) options has remained difficult to compare head-to-head. A large Bayesian network meta-analysis now provides the most statistically robust comparative ranking to date — and its findings challenge some widely held assumptions about oral EC equivalence.
Drawing on 92 randomized controlled trials encompassing 37,260 women, the analysis evaluated copper intrauterine devices (Cu-IUDs), levonorgestrel IUDs (LNG-IUDs), oral levonorgestrel (LNG), mifepristone (MFP), ulipristal acetate (UPA), and oral EC combined with cyclooxygenase inhibitors (COX). The Cu-IUD emerged as the most effective intervention overall, a finding verified through robustness analyses and Bayesian meta-regressions. Notably, combining oral LNG with a COX inhibitor outperformed both single-dose LNG (RR=0.112) and double-dose LNG (RR=0.095) with high-certainty evidence — a combination not routinely offered in most clinical settings. Mifepristone at 25 mg and ulipristal acetate showed comparable efficacy, though mifepristone was associated with advancement of the subsequent menstrual cycle. Evidence for LNG-IUD comparisons was graded low to very low certainty.
This meta-analysis is methodologically significant: Bayesian network frameworks allow indirect treatment comparisons across trials that never directly competed, which is how the LNG-COX finding — arguably the most actionable result — achieved high-certainty status. However, the broader reproductive health field should note that LNG-COX co-treatment remains understudied in real-world rollout contexts, and evidence quality varied substantially across comparisons. The Cu-IUD's superiority is well-established and replicated, but access barriers — cost, insertion requirements, provider availability — mean oral options remain dominant in practice. This analysis is incremental for Cu-IUD and UPA findings, but potentially practice-altering for the LNG-COX combination, which warrants renewed clinical attention.