The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes

Genes (Basel). 2023 Mar 4;14(3):647. doi: 10.3390/genes14030647.


Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500/1000 per male live birth (karyotype 47,XXY). High stature, tiny testicles, small penis, gynecomastia, feminine body proportions and hair, visceral obesity, and testicular failure are all symptoms of KS. Endocrine (osteoporosis, obesity, diabetes), musculoskeletal, cardiovascular, autoimmune disorders, cancer, neurocognitive disabilities, and infertility are also outcomes of KS. Causal theories are discussed in addition to hormonal characteristics and testicular histology. The retrieval of spermatozoa from the testicles for subsequent use in assisted reproduction treatments is discussed in the final sections. Despite testicular atrophy, reproductive treatments allow excellent results, with rates of 40-60% of spermatozoa recovery, 60% of clinical pregnancy, and 50% of newborns. This is followed by a review on the predictive factors for successful sperm retrieval. The risks of passing on the genetic defect to children are also discussed. Although the risk is low (0.63%) when compared to the general population (0.5-1%), patients should be informed about embryo selection through pre-implantation genetic testing (avoids clinical termination of pregnancy). Finally, readers are directed to a number of reviews where they can enhance their understanding of comprehensive diagnosis, clinical care, and fertility preservation.

Keywords: Klinefelter syndrome; epidemiology; etiology; genetic causes; metabolic syndrome; newborn; predictive factors; spermatogenesis; testicular sperm retrieval; testis.

Publication types

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

MeSH terms

  • Child
  • Chromosome Aberrations
  • Female
  • Humans
  • Infant, Newborn
  • Klinefelter Syndrome* / epidemiology
  • Klinefelter Syndrome* / genetics
  • Klinefelter Syndrome* / pathology
  • Male
  • Pregnancy
  • Semen
  • Sperm Retrieval
  • Spermatozoa / pathology
  • Testis / pathology

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The UMIB (Unit for Multidisciplinary Research in Biomedicine) is funded by the Foundation for Science and Technology (FCT) Portugal (grant numbers UIDB/00215/2020 and UIDP/00215/2020) and ITR (Laboratory for Integrative and Translational Research in Population Health) (LA/P/0064/2020).