The genetic aetiology of male infertility: clinical and forensic implications

The escalating prevalence of infertility on a global scale represents a critical public concern, with over 50% cases attributed to male-related factors. Y chromosome microdeletion, within the azoospermia factor region, has emerged as a significant genetic contributor to male infertility, with its occurrence varying from 2% to 24% based on the geographic location and genetic background. The prevalence of such microdeletions in infertile individuals varies broadly, with AZFc being the most frequently reported deletion. The gr/gr partial deletion demonstrates a significant ethnic correlation, highlighting the genetic and demographic factors that may influence microdeletions in the AZF region. Reports also indicate significant geographical variation, with eastern and southern areas exhibiting higher prevalence, in contrast to Europe and Australia. In the Clinical aspect, the deletion is a reliable diagnostic tool for identifying infertility and its genetic causes, making it essential for accurate diagnosis and genetic counselling. Moreover, this review addresses challenges associated with the complex Y-Short Tandem Repeat profile interpretation, as well as their potential implication in forensic and medical genetics. The key focus is to investigate the uniparental inheritance of the Y chromosome, its importance in tracing the male lineage, identification of perpetrators in sexual assault cases, and in investigative genetic genealogy. However, the deletion results in an atypical profile pattern, thereby necessitating careful validation strategies to prevent interpretational errors in forensic and kinship analysis. In conclusion, establishing a standardised screening protocol, a unified testing threshold, and centralising the genetic database are essential for improving health management and forensic justice.