Non-Inferiority Analysis of Levonorgestrel IUD Versus Oral Levonorgestrel for Emergency Contraception: A Systematic Review and Meta-Analysis

Abstract

Introduction: Emergency contraception (EC) is a critical component of reproductive healthcare, with currently approved oral options including levonorgestrel (LNG) and ulipristal acetate. Although effective, oral EC methods demonstrate reduced efficacy with increasing time since intercourse and higher body mass index (BMI). In contrast, intrauterine devices (IUD), particularly the copper IUD, provide highly effective EC. Emerging evidence suggests that the levonorgestrel IUD may also be a non-inferior option. This systematic review and meta-analysis examined the comparative efficacy of the LNG-IUD versus oral LNG for EC. Methods: Following PRISMA guidelines, PubMed, Scopus, Medline, and ClinicalTrials.gov were searched through December 2024. Five studies (n = 920) met inclusion criteria and were evaluated for risk of bias using the Mixed Methods Appraisal Tool (MMAT). Using a random-effects meta-analysis, we estimated pooled pregnancy proportions with 95% confidence intervals, assessed heterogeneity and publication bias, and conducted a non-inferiority test with a 1% margin to compare the effectiveness of the levonorgestrel IUD versus oral levonorgestrel for EC. Results: This study found an overall pregnancy proportion ≤1%, with no significant differences among LNG-IUD, oral LNG, and copper IUD groups. Non-inferiority testing demonstrated that the LNG-IUD was non-inferior to oral LNG, as the upper bound of the pooled difference (0.008) remained below the 1% margin. Conclusion: Despite limited direct comparison studies requiring subgroup formation, these findings indicate that the LNG-IUD does not confer a clinically meaningful increase in pregnancy risk compared with oral LNG when used for EC. The findings suggest that LNG-IUD could be a promising alternative to oral LNG for EC, offering both immediate and long-term contraception. Further large-scale, direct comparative studies are warranted to expand EC options for women.