Sperm telomere length: A potential reflection of genomic integrity and environmental influences on male fertility.

Infertility affects nearly one in six people worldwide, with male-related factors contributing to approximately half of all cases. Although conventional semen analysis remains central to the assessment of male fertility, it provides limited insight into sperm genomic competence and has only modest value for predicting reproductive outcomes. Sperm telomere length (STL) has therefore gained attention as a potential marker of germ-cell history, genomic integrity, and cumulative exposure to environmental and metabolic stress. Evidence from human studies, however, remains inconsistent. Associations between STL, conventional semen parameters, and assisted reproductive technology (ART) outcomes vary across studies, likely because of differences in study populations, sperm preparation and purification methods, somatic-cell contamination, sample size, confounder adjustment, outcome definitions, and analytical platforms. Among the most widely used methods, quantitative polymerase chain reaction (qPCR) provides a relative estimate of mean telomere length based on the telomere-to-single-copy-gene (T/S) ratio in bulk samples, whereas quantitative fluorescence in situ hybridization (qFISH) enables assessment of telomere-signal distributions at the single-cell level. Both approaches offer distinct advantages and limitations, and neither has demonstrated clear clinical superiority. This review integrates current biological, methodological, environmental, and clinical evidence and proposes a cautious mechanistic framework linking oxidative stress, mitochondrial dysfunction, telomeric DNA damage, chromatin organization, STL variation, and reproductive outcomes. While STL is biologically plausible as an investigational marker of sperm quality, current evidence is insufficient to support its routine clinical use. Larger, standardized, and well-controlled studies are needed to establish whether STL provides meaningful information beyond existing measures of male fertility.