Sperm DNA fragmentation and embryo aneuploidy: a comprehensive systematic review and meta-analysis

ABSTRACT Research Question What is the association between an elevated sperm DNA fragmentation index (DFI) and the risk of embryonic aneuploidy in couples undergoing assisted reproductive technology (ART)? Design This PROSPERO-registered systematic review and meta-analysis (CRD420251067930) searched PubMed, Embase, Cochrane Library, and Web of Science up to 10 July 2025 for observational studies. Studies were included if they reported on couples undergoing ART with sperm DFI testing and preimplantation genetic testing. Heterogeneity was explored via prespecified subgroup analyses. Robustness was evaluated through sensitivity analyses (leave-one-out method) and assessment of publication bias using funnel plots and Egger's test. Results From 601 records, 11 studies were systematically reviewed. Meta-analysis of 7 studies (3,563 embryos) revealed a significant, albeit modest, positive association (pooled RR = 1.16, 95% CI: 1.03–1.31), with considerable heterogeneity (I² = 55%). The significance of this association varied across subgroups. No significant publication bias was detected, and sensitivity analyses confirmed the robustness of the primary finding. Conclusions Current evidence, derived solely from retrospective studies, establishes a modest link but is insufficient to recommend sperm DFI testing as an independent guide for clinical decisions, highlighting the need for prospective validation.