Male fertility restoration with stem cell-based therapies: from testicular stem cells to pluripotent stem cell-based in vitro gametogenesis.

Male factor infertility poses a substantial clinical challenge, affecting 8%-12% of couples worldwide. The underlying causes of this condition range from cancer treatments to congenital disorders. The present approach to fertility preservation entails the cryopreservation of sperm for postpubertal males. However, this method offers limited options for prepubertal patients and those with nonobstructive azoospermia. This review examines emerging stem cell-based therapies, including testicular tissue grafting, organ culture, cell reconstitution, spermatogonial stem cell transplantation, and pluripotent stem cell-derived in vitro gametogenesis. Although these approaches have demonstrated notable efficacy in animal models, particularly in mice, translating these technologies into clinical applications is confronted by significant scientific, ethical, and regulatory challenges. These innovative stem cell strategies offer promising pathways to restore fertility potential and provide hope for patients currently without reproductive options.