Genetics of male infertility – Present and future: A narrative review

Infertility affects 8%–12% of couples worldwide with a male factor contributing to nearly 50% of couples either as a primary or contributing cause. Several genetic factors that include single-gene and multiple-gene defects associated with male infertility were reported in the past two decades. However, the etiology remains ambiguous in a majority of infertile men (~40%). The objective of this narrative review is to provide an update on the genetic factors associated with idiopathic male infertility and male reproductive system abnormalities identified in the last two decades. We performed a thorough literature search in online databases from January 2000 to July 2021. We observed a total of 13 genes associated with nonobstructive azoospermia due to maturation/meiotic arrest. Several studies that reported novel genes associated with multiple morphological abnormalities of the sperm flagella are also discussed in this review. ADGRG2, PANK2, SCNN1B, and CA12 genes are observed in non-CFTR-related vas aplasia. The genomic analysis should be quickly implemented in clinical practice as the detection of gene abnormalities in different male infertility phenotypes will facilitate genetic counseling.