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Fertility Preservation

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

Abstract

Most of men with non-mosaic Klinefelter syndrome (KS) are azoospermic and for many decades use of donor semen was the only possible way of becoming a father for KS men. In the last 20 years, hundreds of non-mosaic azoospermic KS men have been submitted to testicular sperm extraction (TESE) and an overall sperm retrieval rate (SRR) of approximately 40% per TESE cycle has been recently reported. Data about pregnancy rate and live birth rate after intracytoplamic sperm injection (ICSI) support now the notion that KS men should not be considered anymore infertile. SSR appears to be independent of surgical procedure (TESE or micro-TESE) and patient age, suggesting that the focal spermatogenesis in KS testes does not undergo a progressive seminiferous tubule hyalinization. Undefined yet is whether it is necessary to perform TESE before initiating testosterone therapy in hypogonadal KS men, or whether it is safe to wait until paternity is wished by interruption of testosterone treatment. TESE technique holds a risk for inducing or aggravating androgen deficiency in KS, independently of the surgical technique, indicating the need of endocrine monitoring after TESE to initiate testosterone treatment if needed. Of note, although TESE-ICSI gives the chance for an eventually normal live birth in non-mosaic KS men, it should be considered that the cumulative delivery rates per patient submitted to TESE is approximately 16% or lower. Prior to undergoing TESE, patients should be counseled that the majority of them will probably not father a genetically proper child.

Keywords

  • Klinefelter syndrome
  • Testicular sperm extraction
  • Intracytoplamic sperm injection
  • Sperm retrieval rate
  • Testosterone
  • Hypogonadism

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References

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

    CrossRef  CAS  PubMed  Google Scholar 

  2. Rohayem J, Fricke R, Czeloth K, Mallidis C, Wistuba J, Krallmann C, Zitzmann M, Kliesch S. Age and markers of Leydig cell function, but not of Sertoli cell function predict the success of sperm retrieval in adolescents and adults with Klinefelter’s syndrome. Andrology. 2015;3:868–75.

    CrossRef  CAS  PubMed  Google Scholar 

  3. Aksglaede L, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168(4):R67–76.

    CrossRef  CAS  PubMed  Google Scholar 

  4. Tournaye H, Staessen C, Liebaers I, Van Assche E, Devroey P, Bonduelle M, Van Steirteghem A. Testicular sperm recovery in nine 47,XXY Klinefelter patients. Hum Reprod. 1996;11:1644–9.

    CrossRef  CAS  PubMed  Google Scholar 

  5. 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.

    CrossRef  CAS  PubMed  Google Scholar 

  6. Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Magi M, et al. Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2017;23:265–75.

    CrossRef  CAS  PubMed  Google Scholar 

  7. Aksglaede L, Wikstrom AM, Rajpert-De ME, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update. 2006;12:39–48.

    CrossRef  PubMed  Google Scholar 

  8. Van Saen D, Vloeberghs V, Gies I, Mateizel SK, De Schepper J, Tournaye H, Goossens E. When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome? Hum Reprod. 2018;33(6):1009–22.

    CrossRef  PubMed  CAS  Google Scholar 

  9. Winge SB, Dalgaard MD, Jensen JM, Graem N, Schierup MH, Juul A, Raipert-De Meyts E, Almstrup K. Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible involvement of long non-coding RNAs in gonocyte maturation. Hum Mol Genet. 2017;27:430–9.

    CrossRef  CAS  Google Scholar 

  10. Ross JL, Samango-Sprouse C, Lahlou N, Kowal K, Elder FF, Zinn A. Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome. Horm Res. 2005;64:39–45.

    CAS  PubMed  Google Scholar 

  11. Zeger MP, Zinn AR, Lahlou N, Ramos P, Kowal K, Samango Sprouse C, Ross JL. Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome. J Pediatr. 2008;152:716–22.

    CrossRef  PubMed  Google Scholar 

  12. 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;89:2263–70.

    CrossRef  PubMed  CAS  Google Scholar 

  13. Wikstrom AM, Hoei-Hansen CE, Dunkel L, Rajpert-De ME. Immunoexpression of androgen receptor and nine markers of maturation in the testes of adolescent boys with Klinefelter syndrome: evidence for degeneration of germ cells at the onset of meiosis. J Clin Endocrinol Metab. 2006;92:714–9.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Franik S, Hoeijmakers Y, D’Hauwers K, Braat DD, Nelen WL, Smeets D, Claahsen-van der Grinten HL, Ramos L, Fleischer K. Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome. Hum Reprod. 2016;31(9):1952–9.

    CrossRef  CAS  PubMed  Google Scholar 

  15. Rohayem J, Nieschlag E, Zitzmann M, Kliesch S. Testicular function during puberty and young adulthood in patients with Klinefelter’s syndrome with and without spermatozoa in seminal fluid. Andrology. 2016;4:1178–86.

    CrossRef  CAS  PubMed  Google Scholar 

  16. Plotton I, Giscard D’Estaing S, Cuzin B, Brosse A, Benchaib M, Lornage J, Ecochard R, Dijoud F, Lejeune H, FERTIPRESERVE Group. 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;100:961–7.

    CrossRef  CAS  PubMed  Google Scholar 

  17. Nahata L, Yu RN, Paltiel HJ, Chow JS, Logvinenko T, Rosoklija I, Cohen LE. Sperm retrieval in adolescents and young adults with Klinefelter syn-drome: a prospective, pilot study. J Pediatr. 2016;170:260–65.e2.

    CrossRef  PubMed  Google Scholar 

  18. Sciurano RB, Luna Hisano CV, Rahn MI, Brugo Olmedo S, Rey Valzacchi G, Coco R, Solari AJ. Focal spermatogenesis originates in euploid germ cellsin classical Klinefelter patients. Hum Reprod. 2009;24:2353–60.

    CrossRef  CAS  PubMed  Google Scholar 

  19. Oates R. Adolescent Klinefelter syndrome: is there an advantage to testis tissue harvesting or not? F1000Res. 2016;5:1595.

    CrossRef  Google Scholar 

  20. Avarbock MR, Brinster CJ, Brinster RL. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med. 1996;2:693–6.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  21. Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A. 1994;91:11298–302.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gies I, De Schepper J, Van Saen D, Anckaert E, Goossens E, Tournaye H. Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47, XXY boys by single testicular biopsy. Hum Reprod. 2012;27:998–1004.

    CrossRef  CAS  PubMed  Google Scholar 

  23. Van Saen D, Gies I, De Schepper J, Tournaye H, Goossens E. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking? Hum Reprod. 2012;27:323–30.

    CrossRef  PubMed  CAS  Google Scholar 

  24. Vloeberghs V, Verheyen G, Santos-Ribeiro S, Staessen C, Verpoest W, Gies I, Tournaye H. Is genetic fatherhood within reach for all azoospermic Klinefelter men? PLoS One. 2018;13(7):e0200300.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  25. Westlander G, Ekerhovd E, Bergh C. Low levels of serum inhibin B do not exclude successful sperm recovery in men with nonmosaic Klinefelter syndrome. Fertil Steril. 2003;79(Suppl 3):1680–2.

    CrossRef  PubMed  Google Scholar 

  26. Madgar I, Dor J, Weissenberg R, Raviv G, Menashe Y, Levron J. Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy. Fertil Steril. 2002;77:1167–9.

    CrossRef  PubMed  Google Scholar 

  27. Schiff JD, Palermo GD, Veeck LL, Goldstein M, Rosenwaks Z, Schlegel PN. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90:6263–7.

    CrossRef  CAS  PubMed  Google Scholar 

  28. Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for Klinefelter’s syndrome. J Urol. 2009;182(3):1108–13.

    CrossRef  CAS  PubMed  Google Scholar 

  29. Mehta A, Bolyakov A, Roosma J, Schlegel PN, Paduch DA. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor. Fertil Steril. 2013;100:970–4.

    CrossRef  CAS  PubMed  Google Scholar 

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

    CrossRef  CAS  PubMed  Google Scholar 

  31. Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertil Steril. 2015;104(5):1099–103.e1-3.

    CrossRef  PubMed  Google Scholar 

  32. Deruyver Y, Vanderschueren D, Van der Aa F. Outcome of microdissection TESE compared with conventional TESE in non-obstructive azoospermia: a systematic review. Andrology. 2014;2(1):20–4.

    CrossRef  CAS  PubMed  Google Scholar 

  33. Ramasamy R, Yagan N, Schlegel PN. Structural and functional changes to the testis after conventional versus microdissection testicular sperm extraction. Urology. 2005;65:1190–4.

    CrossRef  PubMed  Google Scholar 

  34. Shin DH, Turek PJ. Sperm retrieval techniques. Nat Rev Urol. 2013;10:723–30.

    CrossRef  PubMed  Google Scholar 

  35. Eliveld J, van Wely M, Meißner A, Repping S, van der Veen F, van Pelt AMM. The risk of TESE-induced hypogonadism: a systematic review and meta-analysis. Hum Reprod Update. 2018;24(4):442–5.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  36. Bobjer J, Naumovska M, Giwercman YL, Giwercman A. High prevalence of androgen deficiency and abnormal lipid profile in infertile men with non-obstructive azoospermia. Int J Androl. 2012;12(35):688–94.

    CrossRef  CAS  Google Scholar 

  37. Ishikawa T, Yamaguchi K, Chiba K, Takenaka A, Fujisawa M. Serum hormones in patients with nonobstructive azoospermia after microdissection testicular sperm extraction. J Urol. 2009;182:1495–9.

    CrossRef  CAS  PubMed  Google Scholar 

  38. Takada S, Tsujimura A, Ueda T, Matsuoka Y, Takao T, Miyagawa Y, Koga M, Takeyama M, Okamoto Y, Matsumiya K, Fujioka H, Nonomura N, Okuyama A. Androgen decline in patients with nonobstructive azoospemia after microdissection testicular sperm extraction. Urology. 2008;72:114–8.

    CrossRef  PubMed  Google Scholar 

  39. Hessel M, Robben JC, D’Hauwers KW, Braat DD, Ramos L. The influence of sperm motility and cryopreservation on the treatment outcome after intracytoplasmic sperm injection following testicular sperm extraction. Acta Obstet Gynecol Scand. 2015;94:1313–21.

    CrossRef  PubMed  Google Scholar 

  40. 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;31:1934–41.

    CrossRef  CAS  PubMed  Google Scholar 

  41. Vloeberghs V, Verheyen G, Haentjens P, Goossens A, Polyzos NP, Tournaye H. How successful is TESE-ICSI in couples with non-obstructive azoospermia. Hum Reprod. 2015;30(8):1790–6.

    CrossRef  CAS  PubMed  Google Scholar 

  42. Staessen C, Tournaye H, Van Assche E, Michiels A, Van Landuyt L, Devroey P, Liebaers I, Van Steirteghem A. PGD in 47,XXY Klinefelter’s syndrome patients. Hum Reprod Update. 2003;9:319–30.

    CrossRef  CAS  PubMed  Google Scholar 

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Correspondence to Arcangelo Barbonetti .

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Barbonetti, A., D’Andrea, S., Totaro, M., Parisi, A., Salacone, P., Francavilla, S. (2020). Fertility Preservation. 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_22

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  • DOI: https://doi.org/10.1007/978-3-030-51410-5_22

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