Genetic and Molecular Etiologies of Male Infertility: Advances in Diagnosis and Clinical Implications

Male infertility accounts for nearly half of all infertility cases worldwide but remains under-recognised. This review summarises the current genetic and molecular determinants of male infertility and their clinical implications. A comprehensive narrative review was conducted on chromosomal abnormalities, Y-chromosome microdeletions, single-gene mutations, epigenetic alterations, mitochondrial dysfunction and syndromic conditions affecting spermatogenesis. Advances in high-resolution genomic tools, including whole-exome sequencing (WES), next-generation sequencing (NGS) and genomic microarrays, were evaluated alongside assisted reproductive technologies (ARTs) such as intracytoplasmic sperm injection (ICSI) and pre-implantation genetic testing (PGT). Modern genomic technologies enhance diagnostic accuracy and enable personalised reproductive management. Molecular mechanisms, including sperm DNA fragmentation, non-coding RNA regulation and environmentally influenced epigenetic changes, are major contributors to infertility. Integrating molecular diagnostics with ART supports precision-based treatment and genetic counselling. Genetic and molecular insights are transforming male infertility care through individualised diagnostics and targeted interventions. Continued genomic and molecular research will further refine diagnosis, optimise ART outcomes and advance personalised reproductive medicine.