Recurrent pregnancy loss: systematic review and meta-analysis of overall prevalence and the distribution of major etiological categories

复发性流产:总体患病率及主要病因分布的系统评价和荟萃分析

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Abstract

BACKGROUND: Recurrent pregnancy loss (RPL) is a clinically and emotionally significant reproductive condition, yet its reported prevalence and etiological distribution vary widely across studies. This systematic review and meta-analysis aimed to synthesize available evidence on the prevalence of RPL and the pooled proportions of its major etiological categories. METHODS: We conducted a systematic review and meta-analysis of observational studies identified through searches of PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. Random-effects meta-analyses were performed to pool prevalence estimates and etiological proportions using inverse-variance weighting and a restricted maximum likelihood estimator. For prevalence analyses, the denominator corresponded to the total number of individuals screened, as reported by each study. Freeman-Tukey transformations were applied where appropriate. Heterogeneity was assessed using I(2) and τ(2). RESULTS: A total of 105 studies were included, comprising 47,907 women with RPL for etiological analyses. Only two studies provided population-based prevalence estimates of RPL, yielding an estimated prevalence of approximately 1% (95% CI, 1-1%), although the small number of studies limits interpretation. Among women with RPL, the pooled proportion of idiopathic or unexplained RPL was highest (37, 95% CI, 30-44%; I(2) = 94.3%), followed by acquired thrombophilia (12, 95% CI, 9-15%), endocrine factors (8, 95% CI, 6-10%), and anatomical factors and hereditary thrombophilia (6, 95% CI, 5-8%). Subgroup and meta-regression analyses suggested that geographic region and selected demographic and temporal study characteristics may contribute to between-study variability in etiological distributions. CONCLUSION: Reported prevalence and etiological proportions of RPL vary substantially across studies, and a large proportion of cases remain unexplained. The observed heterogeneity, partly associated with regional, demographic, and temporal factors, highlights the need for standardized definitions, diagnostic workups, and reporting practices to improve comparability across studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registry Number: CRD42024517675.

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