Genetic mutations contributing to non-obstructive azoospermia

Best Pract Res Clin Endocrinol Metab. 2020 Dec;34(6):101479. doi: 10.1016/j.beem.2020.101479. Epub 2020 Dec 15.


Non-obstructive azoospermia is a distinct diagnosis within male infertility in which no sperm is found in the ejaculate as a result of spermatogenesis failure. Because of the increased prevalence of genetic abnormalities in men with non-obstructive azoospermia, male infertility guidelines recommend screening for karyotype abnormalities and Y chromosome microdeletions in this population. Numerous karyotype abnormalities may be present resulting in impaired spermatogenesis, including: Klinefelter syndrome, translocations, and deletions. Y chromosome microdeletions of the AZFa, AZFb, AZFc subregions all can also result in non-obstructive azoospermia with the possibility of sperm being present if only the AZFc subregion is deleted. While these are the two genetic tests recommended by the guidelines, nearly 50%-80% of non-obstructive azoospermia has no identifiable cause and is deemed idiopathic. Several other genetic defects can lead to non-obstructive azoospermia including Kallmann syndrome, mild androgen insensitivity syndrome, and TEX11. While many additional candidate genes have been proposed, many have yet to be verified or are so infrequent in the population that screening is cost-ineffective. Much research is still required in the genetics of non-obstructive azoospermia and will require multi-institutional initiatives to better understand the genetics of condition.

Keywords: azoospermia; gene deletion; genetics; infertility; male.

Publication types

  • Review

MeSH terms

  • Androgen-Insensitivity Syndrome / diagnosis
  • Androgen-Insensitivity Syndrome / genetics
  • Azoospermia / diagnosis
  • Azoospermia / epidemiology
  • Azoospermia / genetics*
  • Chromosome Deletion
  • Chromosomes, Human, Y / genetics
  • Diagnosis, Differential
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Humans
  • Infertility, Male / diagnosis
  • Infertility, Male / genetics
  • Klinefelter Syndrome / diagnosis
  • Klinefelter Syndrome / genetics
  • Male
  • Mutation*
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders of Sex Development / diagnosis
  • Sex Chromosome Disorders of Sex Development / genetics
  • Spermatozoa / abnormalities
  • Spermatozoa / metabolism

Supplementary concepts

  • Male sterility due to Y-chromosome deletions