Background: An estimated 17% of all couples worldwide are involuntarily childless (infertile). The clinically identifiable causes of infertility can be found in the male or female partner or in both. The molecular pathophysiology of infertility still remains unclear in many cases but is increasingly being revealed by genetic analyses.
Methods: This review article is based on pertinent publications retrieved by a selective literature search.
Results: The clinical diagnostic evaluation of an infertile couple may yield an indication for genetic analysis. Women with premature ovarian insufficiency should undergo chromosomal analysis and study of the FMR1 gene. If congenital adrenal hyperplasia is suspected, the CYP21A2 gene should be investigated. In men, genetic diagnosis is based primarily on the findings of semen analysis. Klinefelter syndrome and deletions of the Y-chromosomal azoospermia factors may severely limit sperm production. In both male and female partners, the analysis of a gene panel selected on the basis of the individual indication may identify the cause of infertility, e.g., hypogonadotropic hypogonadism, premature ovarian insufficiency, or severe disturbances of spermatogenesis. In some cases, genetic analysis can help determine the likelihood of success of sperm retrieval via testicular biopsy in men, and the potential indication for oocyte cryopreservation in women.
Conclusion: Genetic causes, disease patterns, and the related investigations are becoming increasingly important in the diagnostic evaluation of infertile couples and have implications for further treatment, for the children of the affected couple, and for other family members.