Testing for genetic contributions to infertility: potential clinical impact

Expert Rev Mol Diagn. 2018 Apr;18(4):331-346. doi: 10.1080/14737159.2018.1453358. Epub 2018 Mar 22.

Abstract

Male infertility affects about 7% of the general male population, and it is a multifactorial, polygenic pathological condition. Known genetic factors, accounting for about 20-25% of male factor infertility, are present in each etiological category: i) hypothalamic-pituitary axis dysfunction; ii) quantitative and qualitative alterations of spermatogenesis; iii) ductal obstruction/dysfunction. Areas covered: All routinely available genetic tests are described. Indication for testing for chromosomal anomalies and Y chromosome microdeletions is based on sperm count (severe oligozoospermia/azoospermia). Mutation screening in candidate genes is indicated in specific semen/testis phenotypes. In about 40% of infertile patients, the aetiology remains unknown ('idiopathic cases') and whole exome sequencing may reveal novel genetic causes. Expert commentary: Genetic testing is essential for its relevance in clinical decision-making. For instance, it helps to avoid unnecessary surgical or medical treatments and it may provide prediction for testicular sperm retrieval. The highest frequency of genetic anomalies is observed in severe spermatogenic impairment, which can be treated with in vitro fertilization (IVF). Given the risk of transmitting genetic disorders to the future offspring through IVF, the diagnosis of known and the discovery of novel genetic factors in idiopathic infertility is of outmost clinical importance.

Keywords: Male infertility; Y chromosome; azoospermia; exome; genes; genetics; oligozooseprmia; spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Asthenozoospermia / diagnosis
  • Asthenozoospermia / genetics
  • Azoospermia / diagnosis
  • Azoospermia / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Y / genetics
  • Genetic Testing
  • Gonadotropin-Releasing Hormone / deficiency
  • Gonadotropin-Releasing Hormone / genetics
  • Humans
  • Hypogonadism / diagnosis
  • Hypogonadism / genetics
  • Infertility, Male / diagnosis
  • Infertility, Male / genetics*
  • Kallmann Syndrome / genetics
  • Klinefelter Syndrome / genetics
  • Male
  • Male Urogenital Diseases / genetics
  • Oligospermia / diagnosis
  • Oligospermia / genetics
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders of Sex Development / diagnosis
  • Sex Chromosome Disorders of Sex Development / genetics
  • Sperm Maturation / genetics
  • Sperm Retrieval
  • Spermatogenesis / genetics
  • Teratozoospermia / diagnosis
  • Teratozoospermia / genetics
  • Vas Deferens / abnormalities

Substances

  • Gonadotropin-Releasing Hormone

Supplementary concepts

  • Congenital bilateral aplasia of vas deferens
  • Male sterility due to Y-chromosome deletions