Exome sequencing in a Pakistani male infertility cohort: perspective on molecular diagnosis, genetic heterogeneity, and diagnostic yield

Male infertility affects a significant number of couples worldwide, yet the precise causes and genetic mechanisms underlying this condition remain largely unknown. To investigate the monogenic causes of primary male infertility, we performed exome sequencing (ES) in a cohort of 100 unrelated Pakistani male patients with non-obstructive, non-syndromic primary infertility. ES identified potential causal variants in established infertility-associated genes in 17/100 patients, resulting in a diagnostic yield of 17%. This highlights the effectiveness of next-generation sequencing technologies, particularly the ES approach, in unraveling the genetic basis of male infertility. Overall, this study provides valuable insights into the genetic underpinnings of male infertility. Our findings explore the diagnostic potential of ES and expand the spectrum of causal variants underlying male infertility.