Gene polymorphisms and male infertility – a meta-analysis and literature review

Many genetic polymorphisms have been studied extensively to elucidate their role in the pathophysiology of male infertility. This article presents a review of the literature following a thorough search of PubMed, a compilation of meta-analyses of studies reporting an association with male fertility where the population(s) could be clearly identified as fertile and/or infertile, and a summary of all polymorphisms that have been investigated in single case–control studies to date. The meta-analyses revealed significant associations between polymorphism and male fertility only for AZF gr/gr deletions (OR 1.81, 1.46–2.24 CI, P < 0.00001) and MTHFR 677C→T (OR 1.39, 1.15–2.69 95% CI, P = 0.0006) but not for POLG, DAZL, USP26 or FSHR. The influence of CAG repeat length in AR remains open and debated. Genes encoding nuclear proteins (PRM1/2, TNP1/2) and ER1 are possible candidates for further examination, while the role of TAF7L remains unclear. Polymorphisms in 16 other genes have been investigated in single studies, but the results remain doubtful due to often small and heterogeneous cohorts and in the absence of independent replications. The genetic studies performed so far emphasize the complexity of male infertility as a presumably polygenetic trait amended by environmental, lifestyle or occupational factors.