Male sex reversal syndrome: a disorder of sexual differentiation (DSD) with infertility.

Abstract

46,XX male sex reversal syndrome is a rare genetic disorder where individuals with a 46,XX karyotype present with male phenotypic characteristics despite the absence of an Y chromosome. We report a case of a male in his early 30s, presenting with infertility and azoospermia, with bilateral small testes, but no other sexual dysfunction or any signs of hypovirulisation. His hormonal evaluation revealed hypogonadism with normal gonadotropin levels. Genetic testing showed a 46,XX karyotype with the presence of the sex-determining region on the Y chromosome (SRY) gene and microdeletions in the azoospermia factor region, confirming the diagnosis of SRY-positive 46,XX male sex reversal syndrome. As sperm retrieval was not recommended, the couple pursued donor insemination, resulting in conception during the first cycle. The female partner is now in her third trimester of pregnancy. Testosterone replacement therapy was initiated for hypogonadism, and long-term follow-up was recommended for monitoring therapy and neoplastic risk. This case intends to provide an overview focused on improving diagnostic and management strategies for 46,XX male sex reversal syndrome, emphasising the necessity of genetic evaluation for all patients with hypogonadism and azoospermia presenting with infertility, not limited to those with hypergonadotropic hypogonadism. It also highlights the critical role of a multidisciplinary approach in the effective management of this condition.