Advances in monogenic female infertility

Human reproduction requires the fertilization of a mature oocyte with a sperm to form a high-quality embryo. Oogenesis, folliculogenesis, and the activities of the endocrine system play essential roles in female fertility, and disturbances in these processes can result in female infertility, which has become an urgent public health issue worldwide. Genetic studies have identified multiple variants in key genes underlying these processes in infertile females, and these patients are mainly diagnosed with disorders of sex development, premature ovarian insufficiency, congenital hypogonadotropic hypogonadism, central precocious puberty, resistant ovary syndrome, oocyte maturation arrest, fertilization failure, and early embryonic defects. Notably, the known genes account for about 13.2% cases of oocyte and embryo defects (479/3627) and 18.7% cases of premature ovarian insufficiency (193/1030). Here, we review the critical events in female reproduction and highlight the single gene variants with Mendelian inheritance patterns that are responsible for female infertility.