Abstract
In Klinefelter syndrome (KS) the topic of fertility vs. infertility is of major concern since that, until recent years, infertility was considered an untreatable condition in KS.
Due to chromosome aneuploidy, KS children undergo a progressive testicular impairment leading to spermatogenic failure and infertility (Foresta et al., J Clin Endocrinol Metab 84:3807–3810, 1999). In prepubertal boys with KS a diminished number or complete absence of spermatogonia has been described despite a normal appearance of Sertoli and Leydig cells (Muller et al., Int J Androl 18:57–62, 1995). However, immunohistochemical studies demonstrated that, in early adolescence, the majority of boys with KS have germ cells in their testes despite a marked reduction in adult dark spermatogonia (Muller et al., Int J Androl 18:57–62, 1995; Wikstrom et al. J Clin Endocrinol Metab 89:2263–2270, 2004). Subsequently the onset of puberty is associated with accelerated and progressive depletion of testicular germ cells, which may precede elevation in serum gonadotropin levels (Mehta and Paduch, Fertil Steril 98:274–283, 2012). For these reasons fertility in KS is a major challenge: it is essential to locate the optimal timing to search spermatozoa in KS and the most appropriate technique and modality to give KS subjects the best chance to reach fertility.
Keywords
- Klinefelter syndrome
- Fertility
- Infertility
- Sperm recovery
- TESE
- micro-TESE
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Foresta C, Galeazzi C, Bettella A, Marin P, Rossato M, Garolla A, Ferlin A. Analysis of meiosis in intratesticular germ cells from subjects affected by classic Klinefelter’s syndrome. J Clin Endocrinol Metab. 1999;84(10):3807–10.
Muller J, Skakkebaek NE, Ratcliffe NG. Quantified testicular histology in boys with sex chromosome abnormalities. Int J Androl. 1995;18(2):57–62.
Wikstrom AM, Raivio T, Hadziselimovic F, Wikstrom S, Tuuri T, Dunkel L. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J Clin Endocrinol Metab. 2004;89(5):2263–70.
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364:273–83.
Aksglaede I, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168:R67–76.
Mehta A, Paduch DA. Klinefelter syndrome: an argument for early aggressive hormonal and fertility management. Fertil Steril. 2012;98:274–83.
Hawksworth DJ, Szafran AA, Jordan PW, Dobs AS, Herati AS. Infertility in patients with Klinefelter syndrome: optimal timing for sperm and testicular tissue cryopreservation. Rev Urol. 2018;20(2):56–62.
Garolla A, Selice R, Menegazzo M, Valente U, Zattoni F, Iafrate M, Prayer-Galetti T, Gardiman M, Ferlin A, Di Nisio A, Foresta C. Novel insights on testicular volume and testosterone replacement therapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study. Clin Endocrinol. 2018;88:711–8.
Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pasquali D, Francavilla S. Sperm recovery and ICSI outcome in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2017;23:265–75.
Palermo GD, Schlegel PN, Sills ES, Veeck LL, Zaninovic N, Menendez S, Rosenwaks Z. Births after intracytoplasmic injection of sperm obtained by testicular extraction from men with nonmosaic Klinefelter’s syndrome. N Engl J Med. 1998;338:588–90.
Plotton I, Giscard d’Estaing S, Cuzin B, Brosse A, Benchaib M, Lornage J, Ecochard R, Dijoud F, Lejeune H. Preliminary results of a prospective study of testicular sperm extraction in young versus adult patients with nonmosaic 47,XXY Klinefelter syndrome. J Clin Endocrinol Metab. 2015;100(3):961–7.
Nicopoullos JD, Gilling-Smith C, Almeida PA, Norman-Taylor J, Grace I, Ramsay JW. Use of surgical sperm retrieval in azoospermic men: a meta-analysis. Fertil Steril. 2004;82:691–701.
Plotton I, Brosse A, Cuzin B, Lejeune H. Klinefelter syndrome and TESE-ICSI. Ann Endocrinol. 2014;75:118–25.
Nieschlag E, Ferlin A, Gravholt CH, Gromoll J, Kohler B, Lejeune H, Rogol AD, Wistuba J. The Klinefelter syndrome: current management and research challenges. Andrology. 2016;4:545–9.
McEleny K, Cheetham T, Quinton R. Should we be offering fertility preservation by surgical sperm retrieval to men with Klinefelter syndrome? Clin Endocrinol. 2017;86:463–6.
Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14:131–5.
Paduch DA, Fine RG, Bolyakov A, Kiper J. New concepts in Klinefelter syndrome. Curr Opin Urol. 2008;18:621–7.
Tsujimura A, Matsumiya K, Miyagawa Y, Tohda A, Miura H, Nishimura K, Koga M, Takeyama M, Fujioka H, Okuyama A. Conventional multiple or microdissection testicular sperm extraction: a comparative study. Hum Reprod. 2002;17:2924–9.
Tsujimura A, Miyagawa Y, Takao T, Takada S, Koga M, Takeyama M, Matsumiya K, Fujioka H, Okuyama A. Salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction in patients with nonobstructive azoospermia. J Urol. 2006;175:1446–9.
Cissen M, Meijerink AM, D’Hauwers KW, Meissner A, van der Weide N, Mochtar MH, de Melker AA, Ramos L, Repping S, Braat DD, et al. Prediction model for obtaining spermatozoa with testicular sperm extraction in men with nonobstructive azoospermia. Hum Reprod. 2016;31:1934–194.
Blanco J, Egozcue J, Vidal F. Meiotic behaviour of the sex chromosomes in three patients with sex chromosome anomalies (47,XXY, mosaic 46,XY/47,XXY and 47,XYY) assessed by fluorescence in-situ hybridization. Hum Reprod. 2001;16:887–92.
Westlander G, Ekerhovd E, Granberg S, Hanson L, Hanson C, Bergh C. Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: a prospective study of possible predictive factors for successful sperm recovery. Fertil Steril. 2001;75:1102–5.
Bergere M, Wainer R, Nataf V, Bailly M, Gombault M, Ville Y, et al. Biopsied testis cells of four 47,XXY patients: fluorescence in-situ hybridization and ICSI results. Hum Reprod. 2002;17:32–7.
Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl. 2003;24:41–8.
Abdelmoula NB, Amouri A, Portnoi MF, Saad A, Boudawara T, Mhiri MN, et al. Cytogenetics and fluorescence in situ hybridization assessment of sex-chromosome mosaicism in Klinefelter’s syndrome. Ann Genet. 2004;47:163–75.
Samplaski MK, Lo KC, Grober ED, Millar A, Dimitromanolakis A, Jarvi KA. Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril. 2014;101:950–5.
Visootsak J, Rosner B, Dykens E, Tartaglia N, Graham JM Jr. Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY. Am J Med Genet A. 2007;143A:1198–203.
Heard E, Disteche CM. Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev. 2006;20:1848–67.
Mehta A, Malek-Jones M, Bolyakov A, Mielnik A, Schlegel PN, Paduch DA. Methylation-specific PCR allows for fast diagnosis of X chromosome disomy and reveals skewed inactivation of the X chromosome in men with Klinefelter syndrome. J Androl. 2012;33:955–62.
Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, et al. The DNA sequence of the human X chromosome. Nature. 2005;434:325–37.
Giedd JN, Clasen LS, Wallace GL, Lenroot RK, Lerch JP, Wells EM, et al. XXY (Klinefelter syndrome): a pediatric quantitative brain magnetic resonance imaging case-control study. Pediatrics. 2007;119:e232–40.
Hong YK, Ontiveros SD, Strauss WM. A revision of the human XIST gene organization and structural comparison with mouse Xist. Mamm Genome. 2000;11:220–4.
Condorelli RA, Cannarella R, Calogero AE, La Vignera S. Evaluation of testicular function in prepubertal children. Endocrine. 2018;62:274–80.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Ghezzi, M., Aversa, A., Garolla, A. (2020). Fertility Versus Infertility. In: Garolla, A., Corona, G. (eds) Klinefelter’s Syndrome. Trends in Andrology and Sexual Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-51410-5_23
Download citation
DOI: https://doi.org/10.1007/978-3-030-51410-5_23
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-51409-9
Online ISBN: 978-3-030-51410-5
eBook Packages: MedicineMedicine (R0)