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Summary: Background: Globally, approximately 19.4% of women of reproductive age use intrauterine contraception, encompassing both copper intrauterine devices (Cu-IUDs) and levonorgestrel intrauterine devices (LNG-IUDs). Despite current guidelines endorsing intrauterine contraception as a primary method, there remains debate regarding device selection. Notably, the lack of data regarding reasons for discontinuation has limited previous meta-analyses. This study aims to comprehensively evaluate the potential differences between intrauterine devices using available multinational data, thereby providing a basis for global policy and healthcare services. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for primary studies published from inception to January 13, 2024, with no language or geographic restrictions. The study was registered on PROSPERO (CRD42024496400). We included only randomized controlled trials comparing Cu-IUDs and LNG-IUDs. Data extraction was independently conducted by two reviewers, with unresolved discrepancies referred to a third senior reviewer for consultation. The primary outcome was pregnancy, with secondary outcomes encompassing continuation, reasons for discontinuation, expulsion, satisfaction, and other adverse events. Data were synthesized using a random-effects model. Risk of bias was evaluated with the Cochrane Collaboration's tool, and evidence quality was assessed using the GRADE framework. Findings: An analysis of 20 trials showed that compared to Cu-IUDs, LNG-IUDs were associated with lower risks of pregnancy (Risk Ratio 0.22, 95% confidence interval 0.12–0.39), ectopic pregnancy (RR 0.12, 95% CI 0.03–0.47), discontinuation due to increased bleeding (RR 0.49, 95% CI 0.28–0.85), increased bleeding (RR 0.42, 95% CI 0.25–0.7), heavy bleeding (RR 0.41, 95% CI 0.22–0.75), and dysmenorrhea (RR 0.41, 95% CI 0.34–0.48), but they carried a higher risk of discontinuation due to amenorrhea (RR 21.05, 95% CI 8.83–50.00). When comparing LNG (52 mg) IUD with copper (380 mm2) IUD, The LNG-IUD showed a lower risk of discontinuation due to increased bleeding (RR 0.68, 95% CI 0.55–0.58) and dysmenorrhea (RR 0.42, 95% CI 0.34–0.53), but a higher risk of discontinuation due to bleeding issues (RR 2.83, 95% CI 2.47–3.25) and amenorrhea (RR 5.92, 95% CI 2.81–12.49). There were no significant differences between the two terms of continuation, expulsion, non-medical reasons for discontinuation, satisfaction, and other adverse outcomes. Interpretation: LNG-IUDs and Cu-IUDs are both highly effective contraceptive methods. Compared to Cu-IUDs, LNG-IUDs were associated with a lower risk of pregnancy and adverse reactions. However, LNG-IUDs carry a higher risk of amenorrhea. When recommending contraceptive methods, healthcare providers should fully inform patients of these potential risks and consider patient preferences. Funding: The research was funded by Hunan Provincial Natural Foundation of China (2021JJ30040), the National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University (2021KFJJ06), and the National Natural Science Foundation of China (No. 81672225). |