A systematic review on the genetics of male infertility in the era of next-generation sequencing

OBJECTIVES: To identify the role of next-generation sequencing (NGS) in male infertility, as advances in NGS technologies have contributed to the identification of novel genes responsible for a wide variety of human conditions and recently has been applied to male infertility, allowing new genetic factors to be discovered. MATERIALS AND METHODS: PubMed was searched for combinations of the following terms: ‘exome’, ‘genome’, ‘panel’, ‘sequencing’, ‘whole-exome sequencing’, ‘whole-genome sequencing’, ‘next-generation sequencing’, ‘azoospermia’, ‘oligospermia’, ‘asthenospermia’, ‘teratospermia’, ‘spermatogenesis’, and ‘male infertility’, to identify studies in which NGS technologies were used to discover variants causing male infertility. RESULTS: Altogether, 23 studies were found in which the primary mode of variant discovery was an NGS-based technology. These studies were mostly focused on patients with quantitative sperm abnormalities (non-obstructive azoospermia and oligospermia), followed by morphological and motility defects. Combined, these studies uncover variants in 28 genes causing male infertility discovered by NGS methods. CONCLUSIONS: Male infertility is a condition that is genetically heterogeneous, and therefore remarkably amenable to study by NGS. Although some headway has been made, given the high incidence of this condition despite its detrimental effect on reproductive fitness, there is significant potential for further discoveries.