Innovative treatment approaches for azoospermia: causes, emerging techniques, and future directions

Azoospermia, particularly non-obstructive azoospermia (NOA), is a major cause of male infertility and remains difficult to treat due to its complex hormonal, genetic, and immunological etiologies. The purpose of this review is to examine the biological, hormonal, genetic, and immunological mechanisms underlying azoospermia, with a specific focus on recent advances in regenerative and genetic therapies aimed at restoring spermatogenesis and fertility.This narrative review summarizes and analyzes published experimental, preclinical, and clinical studies focusing on the biological, hormonal, genetic, and immunological aspects of azoospermia, with particular emphasis on emerging regenerative and genetic therapeutic approaches.The reviewed highlights that non-obstructive azoospermia results from multifactorial disturbances involving hormonal imbalance, genetic defects, immune dysregulation, and disruption of the testicular microenvironment. The literature discussed in this review indicates that regenerative strategies such as platelet-rich plasma, stem cell-based approaches, and extracellular vesicles may contribute to testicular repair and support spermatogenic processes through modulation of cellular signaling and inflammatory pathways. In parallel, advances in genetic technologies, particularly CRISPR-based gene-editing tools, are presented as emerging strategies for targeting genes essential for spermatogenesis.Although clinical application remains early, these strategies show strong potential in reversing testicular damage. Continued research and clinical trials are essential to confirm safety, optimize protocols, and expand therapeutic use.