Male infertility is a multifactorial and heterogeneous pathological condition affecting 7% of the general male population. The genetic landscape of male infertility is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2000 genes are predicted to be involved in spermatogenesis. Genetic factors have been described in each etiological category of male reproductive impairment: (1) hypothalamic-pituitary axis dysfunction; (2) quantitative and qualitative alterations of spermatogenesis; (3) ductal obstruction/dysfunction. In 25% of azoospermic and in 10% of oligozoospermic men, a genetic anomaly can be diagnosed with the current genetic testing. However, up to now, only a relatively low number of monogenic factors have a clear-cut cause-effect relationship with impaired reproductive function. Thanks to the widespread diffusion of Next-Generation Sequencing, a continuously increasing number of monogenic causes of male infertility are being discovered and their validation is currently ongoing. The identification of genetic factors is of outmost clinical importance since there is a risk of transmission of genetic defects through natural or assisted reproductive techniques. The benefit of the genetic diagnosis of infertility has an obvious clinical significance for the patient itself with implications not only for his reproductive health but in many instances also for his general health.
Keywords: Azoospermia; Exome; Gene; Genetics; Hypogonadism; Male infertility; NGS; Oligozoospermia; Spermatogenesis; Teratozoospermia.