Background: Male infertility affects nearly 15% of couples globally, with genetic causes contributing substantially to azoospermia and severe oligospermia. Microdeletions in the Azoospermia Factor (AZF) regions of the Y chromosome, particularly on the long arm (Yq), constitute the second most common genetic cause of spermatogenic failure. These deletions disrupt critical genes responsible for testicular development and spermatogenesis, resulting in heterogeneous clinical and histopathological presentations. This review synthesizes updated knowledge on the epidemiology, phenotypic spectrum, and diagnostic advancements related to Yq AZF microdeletions.

Methods: A comprehensive literature search was performed across SciFinder, Google Scholar, MEDLINE, EMBASE, and Scopus databases using predefined keywords, including “AZF,” “Y chromosome microdeletion,” “azoospermia,” “oligospermia,” “diagnostics,” and “spermatogenesis.” Studies published up to May 2021 and restricted to the English language were screened following a structured eligibility flowchart. A total of 109 studies were included after rigorous selection.

Results: Evidence indicates that AZFa, AZFb, and AZFc microdeletions exhibit distinct gene losses, phenotypes, and clinical outcomes. AZFc deletions are the most frequent (≈60%), while AZFa deletions, though rare, often lead to Sertoli-cell-only syndrome. Diagnostic approaches have evolved from conventional semen analysis to advanced molecular tools such as sequence-tagged site PCR, quantitative fluorescent PCR, and fluorescence in situ hybridization. These techniques enable accurate detection of microdeletions and guide reproductive counseling, particularly regarding assisted reproductive technologies and vertical transmission risks.

Conclusion: Yq AZF microdeletions represent a major genomic cause of male infertility, with significant implications for diagnosis, prognosis, and genetic counseling. Continued refinement of molecular diagnostics and exploration of genotype–phenotype correlations are crucial for improving patient management and understanding the broader genetic architecture of spermatogenic failure.

Keywords: Yq AZF Microdeletions, Male Infertility 

To be Updated