Living Reference Work Entry

Endocrinology of the Testis and Male Reproduction

Part of the series Endocrinology pp 1-21

Date: Latest Version

Genetics of Male Infertility

  • Frank TüttelmannAffiliated withInstitute of Human Genetics, University of Münster Email author 
  • , Albrecht RöpkeAffiliated withInstitute of Human Genetics, University of Münster


Male infertility may be caused by genetic defects that increase in prevalence when spermatogenesis is severely impaired. Thus, especially infertile men with severe oligozoospermia or azoospermia should be investigated by cytogenetic and molecular genetic analysis. Structural chromosomal aberrations (e.g., balanced translocations) are found significantly more frequently in oligo- and azoospermic men and numerical chromosomal aberrations of the sex chromosomes, especially Klinefelter syndrome (karyotype 47,XXY), are common among azoospermic men. Screening for Y-chromosomal AZF (“AZoospermia Factor”) deletions is warranted in all men with severe oligo- or azoospermia. Infertile men with obstructive azoospermia should be evaluated for mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Detecting chromosomal aberrations, AZF deletions, and CFTR mutations has important prognostic value for the subsequent work-up and especially for genetic counseling about risk for offspring. Patients with Congenital Hypogonadotropic Hypogonadism (CHH), other syndromic forms of male infertility, or infertile men with rare monomorphic defects of spermatozoa should be carefully investigated for the underlying genetic cause. In the near future, men with severe spermatogenic failure may be evaluated by targeted sequencing of a panel of genes.


Male infertility Chromosomal aberrations Sex chromosomes Klinefelter syndrome AZF deletions CBAVD CFTR Congenital hypogonadotropic hypogonadism Kallmann syndrome