GENEDIS 2026 – Paper 183 – Telomere Dynamics in Male Infertility: A Systematic Review and Meta-Analysis of Reproductive Aging, Semen Quality, and Fertility Outcomes

Telomere biology has emerged as a potential molecular link between reproductive aging, sperm genomic integrity, and male infertility, yet findings remain heterogeneous across reproductive phenotypes, biological compartments, and analytical methods. This systematic review and meta-analysis synthesized human evidence on telomere length in relation to male infertility, semen quality, reproductive aging, sperm genomic integrity, and fertility-related outcomes. PubMed/MEDLINE, Scopus, and Web of Science were searched through 1 October 2026 in accordance with PRISMA 2020 and PRISMA-S. Forty-seven studies met the eligibility criteria. Sperm telomere length (STL), leukocyte telomere length, and testicular or spermatogenic-cell telomere measures were evaluated separately. Fourteen studies contributed to the primary random-effects meta-analysis comparing STL between men with infertility or impaired reproductive/semen phenotypes and fertile or normozoospermic controls. STL was significantly shorter in reproductively impaired men (Hedges’ g = −1.56, 95% CI −2.47 to −0.66; p = 0.003), although heterogeneity was substantial (I² = 95.6%; 95% prediction interval −4.97 to 1.84). The association remained significant across multiple sensitivity analyses. Secondary evidence indicated phenotype-dependent relationships between STL and semen parameters, a general tendency toward age-related STL elongation, and recurrent associations between telomere dysfunction, oxidative stress, DNA fragmentation, chromatin abnormalities, and mitochondrial dysfunction. Evidence for leukocyte telomere length and assisted-reproduction outcomes was less consistent. Overall, shorter STL represents a reproducible but non-universal feature of male reproductive impairment, supporting telomere dysfunction as one component of a broader reproductive phenotype. STL may have value as a complementary molecular marker, particularly where conventional semen analysis provides incomplete biological information, but clinical translation requires methodological standardization, prospective validation, and demonstration of incremental clinical utility.