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Fertility Versus Infertility

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Klinefelter’s Syndrome

Part of the book series: Trends in Andrology and Sexual Medicine ((TASM))

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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.

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References

  1. 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.

    CAS  PubMed  Google Scholar 

  2. Muller J, Skakkebaek NE, Ratcliffe NG. Quantified testicular histology in boys with sex chromosome abnormalities. Int J Androl. 1995;18(2):57–62.

    Article  CAS  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364:273–83.

    Article  CAS  Google Scholar 

  5. Aksglaede I, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168:R67–76.

    Article  CAS  Google Scholar 

  6. Mehta A, Paduch DA. Klinefelter syndrome: an argument for early aggressive hormonal and fertility management. Fertil Steril. 2012;98:274–83.

    Article  Google Scholar 

  7. 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.

    PubMed  PubMed Central  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. Plotton I, Brosse A, Cuzin B, Lejeune H. Klinefelter syndrome and TESE-ICSI. Ann Endocrinol. 2014;75:118–25.

    Article  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14:131–5.

    Article  CAS  Google Scholar 

  17. Paduch DA, Fine RG, Bolyakov A, Kiper J. New concepts in Klinefelter syndrome. Curr Opin Urol. 2008;18:621–7.

    Article  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl. 2003;24:41–8.

    Article  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. Heard E, Disteche CM. Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev. 2006;20:1848–67.

    Article  CAS  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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.

    Article  CAS  Google Scholar 

  31. 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.

    Article  Google Scholar 

  32. 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.

    Article  CAS  Google Scholar 

  33. Condorelli RA, Cannarella R, Calogero AE, La Vignera S. Evaluation of testicular function in prepubertal children. Endocrine. 2018;62:274–80.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Unit of Andrology and Reproductive Medicine and Centre for Male Gamete Cryopreservation, University of Padua, Padua, Italy

    Marco Ghezzi & Andrea Garolla

  2. Department of Experimental and Clinical Medicine, Endocrinology Unit, University of Catanzaro Magna Graecia, Catanzaro, Italy

    Antonio Aversa

Authors
  1. Marco Ghezzi
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  2. Antonio Aversa
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  3. Andrea Garolla
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Corresponding author

Correspondence to Andrea Garolla .

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Editors and Affiliations

  1. Unit of Andrology and Reproductive Medicine, University of Padua, Padua, Italy

    Andrea Garolla

  2. Endocrinology Unit, Ospedale Maggiore, Bologna, Italy

    Giovanni Corona

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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

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  • DOI: https://doi.org/10.1007/978-3-030-51410-5_23

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-51409-9

  • Online ISBN: 978-3-030-51410-5

  • eBook Packages: MedicineMedicine (R0)

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