ART strategies in Klinefelter syndrome

Abstract

Purpose

Patients with Klinefelter syndrome (KS) who receive assisted reproductive technology (ART) treatment often experience poor pregnancy rates due to decreased fertilization, cleavage, and implantation rates and even an increased miscarriage rate. Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients. In this review, we summarize the methods for guiding KS patients during ART and for developing optimal strategies for preserving fertility, improving pregnancy rate and live birth rate, and avoiding the birth of KS infants.

Methods

We searched PubMed and Google Scholar publications related to KS patients on topics of controlled ovarian stimulation protocols, sperm extraction, fertility preservation, gamete artificial activation, round spermatid injection (ROSI), and non-invasive prenatal screening (PGD) methods.

Results

This review outlines the different ovulation-inducing treatments for female partners according to the individual sperm status in the KS patient. We further summarize the methods of retrieving sperm, storing, and freezing rare sperm. We reviewed different methods of gamete artificial activation and discussed the feasibility of ROSI for sterile KS patients who absolutely lack sperm. The activation of eggs in the process of intracytoplasmic sperm injection and non-invasive PGD are urgently needed to prevent the birth of KS infants.

Conclusion

The integrated strategies will pave the way for the establishment of ART treatment approaches and improve the clinical outcome for KS patients.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A, et al. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Investig. 2017;40(2):123–34. https://doi.org/10.1007/s40618-016-0541-6.

    Article  Google Scholar 

  2. 2.

    Capalbo A, Hoffmann ER, Cimadomo D, Ubaldi FM, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23(6):706–22. https://doi.org/10.1093/humupd/dmx026.

    Article  PubMed  Google Scholar 

  3. 3.

    Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87(1):81–3.

    PubMed  Google Scholar 

  4. 4.

    Abramsky L, Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn. 1997;17(4):363–8.

    PubMed  Google Scholar 

  5. 5.

    Grace RJ. Klinefelter’s syndrome: a late diagnosis. Lancet. 2004;364(9430):284. https://doi.org/10.1016/S0140-6736(04)16679-8.

    Article  PubMed  Google Scholar 

  6. 6.

    Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83. https://doi.org/10.1016/S0140-6736(04)16678-6.

    Article  PubMed  Google Scholar 

  7. 7.

    Ferlin A, Schipilliti M, Di Mambro A, Vinanzi C, Foresta C. Osteoporosis in Klinefelter’s syndrome. Mol Hum Reprod. 2010;16(6):402–10. https://doi.org/10.1093/molehr/gaq026.

    Article  PubMed  Google Scholar 

  8. 8.

    Hieronimus S, Lussiez V, Le Duff F, Ferrari P, Bstandig B, Fenichel P. Klinefelter's syndrome and bone mineral density: is osteoporosis a constant feature? Ann Endocrinol. 2011;72(1):14–8. https://doi.org/10.1016/j.ando.2010.10.002.

    Article  Google Scholar 

  9. 9.

    Greco E, Rienzi L, Ubaldi F, Tesarik J. Klinefelter’s syndrome and assisted reproduction. Fertil Steril. 2001;76(5):1068–9.

    PubMed  Google Scholar 

  10. 10.

    Radicioni AF, Ferlin A, Balercia G, Pasquali D, Vignozzi L, Maggi M, et al. Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J Endocrinol Investig. 2010;33(11):839–50. https://doi.org/10.1007/BF03350351.

    Article  Google Scholar 

  11. 11.

    Nieschlag E, Ferlin A, Gravholt CH, Gromoll J, Kohler B, Lejeune H, et al. The Klinefelter syndrome: current management and research challenges. Andrology. 2016;4(3):545–9. https://doi.org/10.1111/andr.12208.

    Article  PubMed  Google Scholar 

  12. 12.

    Selice R, Di Mambro A, Garolla A, Ficarra V, Iafrate M, Ferlin A, et al. Spermatogenesis in Klinefelter syndrome. J Endocrinol Investig. 2010;33(11):789–93. https://doi.org/10.3275/6935.

    Article  Google Scholar 

  13. 13.

    Maiburg M, Repping S, Giltay J. The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertil Steril. 2012;98(2):253–60. https://doi.org/10.1016/j.fertnstert.2012.06.019.

    Article  PubMed  Google Scholar 

  14. 14.

    Franik S, Smeets D, van de Zande G, Gomes I, D'Hauwers K, Braat DDM, et al. Klinefelter syndrome and fertility-impact of X-chromosomal inheritance on spermatogenesis. Andrologia. 2018;50(5):e13004. https://doi.org/10.1111/and.13004.

    Article  PubMed  Google Scholar 

  15. 15.

    Aksglaede L, Andersson AM, Jorgensen N, Jensen TK, Carlsen E, McLachlan RI, et al. Primary testicular failure in Klinefelter’s syndrome: the use of bivariate luteinizing hormone-testosterone reference charts. Clin Endocrinol. 2007;66(2):276–81. https://doi.org/10.1111/j.1365-2265.2006.02722.x.

    Article  Google Scholar 

  16. 16.

    Aksglaede L, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168(4):R67–76. https://doi.org/10.1530/EJE-12-0934.

    Article  PubMed  Google Scholar 

  17. 17.

    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. https://doi.org/10.1016/j.juro.2009.05.019.

    Article  PubMed  Google Scholar 

  18. 18.

    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(4):970–4. https://doi.org/10.1016/j.fertnstert.2013.06.010.

    Article  PubMed  Google Scholar 

  19. 19.

    Nawroth F, Isachenko V, Dessole S, Rahimi G, Farina M, Vargiu N, et al. Vitrification of human spermatozoa without cryoprotectants. Cryo-Letters. 2002;23(2):93–102.

    PubMed  Google Scholar 

  20. 20.

    Hallak J, Sharma RK, Wellstead C, Agarwal A. Cryopreservation of human spermatozoa: comparison of TEST-yolk buffer and glycerol. Int J Fertil Women’s Med. 2000;45(1):38–42.

    Google Scholar 

  21. 21.

    Hsieh Y, Tsai H, Chang C, Lo H. Cryopreservation of human spermatozoa within human or mouse empty zona pellucidae. Fertil Steril. 2000;73(4):694–8.

    PubMed  Google Scholar 

  22. 22.

    Liu J, Zheng XZ, Baramki TA, Compton G, Yazigi RA, Katz E. Cryopreservation of a small number of fresh human testicular spermatozoa and testicular spermatozoa cultured in vitro for 3 days in an empty zona pellucida. J Androl. 2000;21(3):409–13.

    PubMed  Google Scholar 

  23. 23.

    Schuster TG, Keller LM, Dunn RL, Ohl DA, Smith GD. Ultra-rapid freezing of very low numbers of sperm using cryoloops. Hum Reprod. 2003;18(4):788–95.

    PubMed  Google Scholar 

  24. 24.

    Herrler A, Eisner S, Bach V, Weissenborn U, Beier HM. Cryopreservation of spermatozoa in alginic acid capsules. Fertil Steril. 2006;85(1):208–13. https://doi.org/10.1016/j.fertnstert.2005.06.049.

    Article  PubMed  Google Scholar 

  25. 25.

    Cohen J, Garrisi GJ, Congedo-Ferrara TA, Kieck KA, Schimmel TW, Scott RT. Cryopreservation of single human spermatozoa. Hum Reprod. 1997;12(5):994–1001.

    PubMed  Google Scholar 

  26. 26.

    Montag M, Rink K, Dieckmann U, Delacretaz G, van der Ven H. Laser-assisted cryopreservation of single human spermatozoa in cell-free zona pellucida. Andrologia. 1999;31(1):49–53.

    PubMed  Google Scholar 

  27. 27.

    Isachenko V, Isachenko E, Katkov II, Montag M, Dessole S, Nawroth F, et al. Cryoprotectant-free cryopreservation of human spermatozoa by vitrification and freezing in vapor: effect on motility, DNA integrity, and fertilization ability. Biol Reprod. 2004;71(4):1167–73. https://doi.org/10.1095/biolreprod.104.028811.

    Article  PubMed  Google Scholar 

  28. 28.

    Chen Y, Li L, Qian Y, Xu C, Zhu Y, Huang H, et al. Small-volume vitrification for human spermatozoa in the absence of cryoprotectants by using Cryotop. Andrologia. 2015;47(6):694–9. https://doi.org/10.1111/and.12320.

    Article  PubMed  Google Scholar 

  29. 29.

    Walmsley R, Cohen J, Ferrara-Congedo T, Reing A, Garrisi J. The first births and ongoing pregnancies associated with sperm cryopreservation within evacuated egg zonae. Hum Reprod. 1998;13(Suppl 4):61–70.

    PubMed  Google Scholar 

  30. 30.

    Endo Y, Fujii Y, Kurotsuchi S, Motoyama H, Funahashi H. Successful delivery derived from vitrified-warmed spermatozoa from a patient with nonobstructive azoospermia. Fertil Steril. 2012;98(6):1423–7. https://doi.org/10.1016/j.fertnstert.2012.07.1128.

    Article  PubMed  Google Scholar 

  31. 31.

    Peng QP, Cao SF, Lyu QF, Xue SG, Jin W, Liu XY, et al. A novel method for cryopreservation of individual human spermatozoa. In Vitro Cellular Develop Biol Animal. 2011;47(8):565–72. https://doi.org/10.1007/s11626-011-9428-1.

    Article  Google Scholar 

  32. 32.

    Greco E, Litwicka K, Ferrero S, Baroni E, Sapienza F, Rienzi L, et al. GnRH antagonists in ovarian stimulation for ICSI with oocyte restriction: a matched, controlled study. Reprod BioMed Online. 2007;14(5):572–8.

    PubMed  Google Scholar 

  33. 33.

    Rashid MRZ, Ong FB, Omar MH, Ng SP, Nurshaireen A, Sharifah-Teh NSMN, et al. GnRH agonist and GnRH antagonist in intracytoplasmic injection cycles. Med J Malays. 2008;63(2):113–7.

    Google Scholar 

  34. 34.

    Moez K, Meriem E, Fethi Z, Amel Z. Short vs long agonist protocols in poor responders undergoing IVF. La Tunisie Medicale. 2014;92(10):604.

    Google Scholar 

  35. 35.

    Ochin H, Ma X, Wang L, Li X, Song J, Meng Y, et al. Low dose clomiphene citrate as a mild stimulation protocol in women with unsuspected poor in vitro fertilization result can generate more oocytes with optimal cumulative pregnancy rate. J Ovarian Res. 2018;11(1):37.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Reyftmann L, Déchaud H, Loup V, Anahory T, Brunet-Joyeux C, Lacroix N, et al. Natural cycle in vitro fertilization cycle in poor responders. Gynecol Obstet Fertil. 2007;35(4):352–8.

    PubMed  Google Scholar 

  37. 37.

    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. https://doi.org/10.1210/jc.2003-031725.

    Article  PubMed  Google Scholar 

  38. 38.

    Gurbuz AS, Salvarci A, Ozcimen N, Zamani AG. Early morphokinetic monitoring of embryos after intracytoplasmic sperm injection with fresh ejaculate sperm in nonmosaic Klinefelter syndrome: a different presentation. Case Reports Genet. 2015;2015:827656–4. https://doi.org/10.1155/2015/827656.

    Article  Google Scholar 

  39. 39.

    Wu FC, Bancroft J, Davidson DW, Nicol K. The behavioural effects of testosterone undecanoate in adult men with Klinefelter’s syndrome: a controlled study. Clin Endocrinol. 1982;16(5):489–97.

    Google Scholar 

  40. 40.

    Cruger D, Toft B, Agerholm I, Fedder J, Hald F, Bruun-Petersen G. Birth of a healthy girl after ICSI with ejaculated spermatozoa from a man with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2001;16(9):1909–11. https://doi.org/10.1093/humrep/16.9.1909.

    Article  PubMed  Google Scholar 

  41. 41.

    Kitamura M, Matsumiya K, Koga M, Nishimura K, Miura H, Tsuji T, et al. Ejaculated spermatozoa in patients with non-mosaic Klinefelter’s syndrome. Int J Urol. 2000;7(3):88–92.

    PubMed  Google Scholar 

  42. 42.

    Gies I, Unuane D, Velkeniers B, De Schepper J. Management of Klinefelter syndrome during transition. Eur J Endocrinol. 2014;171(2):R67–77. https://doi.org/10.1530/EJE-14-0213.

    Article  PubMed  Google Scholar 

  43. 43.

    Reubinoff BE, Abeliovich D, Werner M, Schenker JG, Safran A, Lewin A. A birth in non-mosaic Klinefelter’s syndrome after testicular fine needle aspiration, intracytoplasmic sperm injection and preimplantation genetic diagnosis. Hum Reprod. 1998;13(7):1887–92.

    PubMed  Google Scholar 

  44. 44.

    Tournaye H, Staessen C, Liebaers I, Van Assche E, Devroey P, Bonduelle M, et al. Testicular sperm recovery in nine 47. XXY Klinefelter patients. Hum Reprod. 1996;11(8):1644–9.

    PubMed  Google Scholar 

  45. 45.

    Palermo GD, Schlegel PN, Sills ES, Veeck LL, Zaninovic N, Menendez S, et al. Births after intracytoplasmic injection of sperm obtained by testicular extraction from men with nonmosaic Klinefelter’s syndrome. N Engl J Med. 1998;338(9):588–90. https://doi.org/10.1056/NEJM199802263380905.

    Article  PubMed  Google Scholar 

  46. 46.

    Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, et al. Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2017;23(3):265–75. https://doi.org/10.1093/humupd/dmx008.

    Article  PubMed  Google Scholar 

  47. 47.

    Paduch DA, Fine RG, Bolyakov A, Kiper J. New concepts in Klinefelter syndrome. Curr Opin Urol. 2008;18(6):621–7. https://doi.org/10.1097/MOU.0b013e32831367c7.

    Article  PubMed  Google Scholar 

  48. 48.

    Franik S, Hoeijmakers Y, D’Hauwers K, Braat DD, Nelen WL, Smeets D, et al. Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome. Hum Reprod. 2016;31(9):dew179.

    Google Scholar 

  49. 49.

    Gies I, Oates R, De Schepper J, Tournaye H. Testicular biopsy and cryopreservation for fertility preservation of prepubertal boys with Klinefelter syndrome: a pro/con debate. Fertil Steril. 2016;105(2):249–55. https://doi.org/10.1016/j.fertnstert.2015.12.011.

    Article  PubMed  Google Scholar 

  50. 50.

    Rohayem J, Fricke R, Czeloth K, Mallidis C, Wistuba J, Krallmann C, et al. 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(5):868–75.

    PubMed  Google Scholar 

  51. 51.

    Cissen M, Meijerink AM, D’Hauwers KW, Meissner A, Van DWN, Mochtar MH, et al. Prediction model for obtaining spermatozoa with testicular sperm extraction in men with non-obstructive azoospermia. Hum Reprod. 2016;31(9):1934.

    PubMed  Google Scholar 

  52. 52.

    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(6):1102–5. https://doi.org/10.1016/s0015-0282(01)01793-9.

    Article  PubMed  Google Scholar 

  53. 53.

    Bergère 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(1):32–7.

    PubMed  Google Scholar 

  54. 54.

    Sciurano RB, Hisano CV, Luna RMI, Olmedo S, Brugo VG, Rey CR, et al. Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients. Hum Reprod. 2009;24(9):2353–60.

    PubMed  Google Scholar 

  55. 55.

    Yasuhisa Y, Nikolaos S, Yasuyuki M, Dimitrios L, Apostolos K, Ikuo M. Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2002;17(4):886–96.

    Google Scholar 

  56. 56.

    Miki T, Nagayoshi M, Takemoto Y. Genetic risk of Klinefelter’s syndrome in assisted reproductive technology. Reproduct Med Biol. 2017;16(2):188–95.

    Google Scholar 

  57. 57.

    Coerdt W, Rehder H, Gausmann I, Johannisson R, Gropp A. Quantitative Histology of Human Fetal Testes in Chromosomal Disease. Pediatr Pathol. 1985;3(2-4):245–59.

    PubMed  Google Scholar 

  58. 58.

    Zondek LH, Zondek T. KLINEFELTER’S SYNDROME IN A FETUS. Lancet. 1974;304:347.

    Google Scholar 

  59. 59.

    Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl. 2003;24(1):41–8.

    PubMed  Google Scholar 

  60. 60.

    Aksglaede L, Jorgensen N, Skakkebaek NE, Juul A. Low semen volume in 47 adolescents and adults with 47,XXY Klinefelter or 46,XX male syndrome. Int J Androl. 2009;32(4):376–84. https://doi.org/10.1111/j.1365-2605.2008.00921.x.

    Article  PubMed  Google Scholar 

  61. 61.

    Nahata L, Yu RN, Paltiel HJ, Chow JS, Logvinenko T, Rosoklija I, et al. Sperm retrieval in adolescents and young adults with Klinefelter syndrome: a prospective, pilot study. J Pediatr. 2016;170:260–5.e2.

    PubMed  Google Scholar 

  62. 62.

    Gies I, Schepper JD, Goossens E, Saen DV, Pennings G, Tournaye H. Spermatogonial stem cell preservation in boys with Klinefelter syndrome: to bank or not to bank, that’s the question. Fertil Steril. 2012;98(2):284–9.

    PubMed  Google Scholar 

  63. 63.

    Shinji K, Isao H, Yukari H, Akiko H, Hiroyuki K, Nobuyuki K, et al. Birth of healthy neonates after intracytoplasmic injection of ejaculated or testicular spermatozoa from men with nonmosaic Klinefelter’s syndrome: a report of 2 cases. J Reprod Med. 2004;49(2):126–30.

    Google Scholar 

  64. 64.

    Bourne H, Stern K, Clarke G, Pertile M, Speirs A, Baker HW. Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47, XXY Klinefelter’s syndrome. Hum Reprod. 1997;12(11):2447–50. https://doi.org/10.1093/humrep/12.11.2447.

    Article  PubMed  Google Scholar 

  65. 65.

    Gérard T, Nelly F, Nicole MD, Anne Le D, Renato F, Michel V, et al. Reproductive genetic counselling in non-mosaic 47,XXY patients: implications for preimplantation or prenatal diagnosis: Case report and review. Hum Reprod. 2003;18(2):271–5.

    Google Scholar 

  66. 66.

    Staessen C, Tournaye H, Assche EV, Michiels A, Landuyt LV, Devroey P, et al. PGD in 47,XXY Klinefelter’s syndrome patient. Hum Reprod Update. 2003;9(4):319–30.

    PubMed  Google Scholar 

  67. 67.

    Sun J, Chen W, Zhou L, Hu J, Li Z, Zhang Z, et al. Successful delivery derived from cryopreserved rare human spermatozoa with novel cryopiece. Andrology. 2017;5(4):832–7.

    PubMed  Google Scholar 

  68. 68.

    Liu F, Zou SS, Zhu Y, Sun C, Liu YF, Wang SS, et al. A novel micro-straw for cryopreservation of small number of human spermatozoon. Asian J Androl. 2017;19(3):326–9.

    PubMed  Google Scholar 

  69. 69.

    Laron Z, Dickerman Z, Zamir R, Galatzer A. Paternity in Klinefelter’s syndrome—a case report. Arch Androl. 1982;8(2):149–51.

    PubMed  Google Scholar 

  70. 70.

    Terzoli G, Lalatta F, Lobbiani A, Simoni G, Colucci G. Fertility in a 47,XXY patient: assessment of biological paternity by deoxyribonucleic acid fingerprinting. Fertil Steril. 1992;58(4):821–2. https://doi.org/10.1016/s0015-0282(16)55334-5.

    Article  PubMed  Google Scholar 

  71. 71.

    Lin YM, Huang WJ, Lin JSN, Kuo PL. Progressive depletion of germ cells in a man with nonmosaic Klinefelter’s syndrome: optimal time for sperm recovery. Urology. 2004;63(2):380–1.

    PubMed  Google Scholar 

  72. 72.

    Fullerton G, Hamilton M, Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009? Hum Reprod. 2010;25(3):588–97.

    PubMed  Google Scholar 

  73. 73.

    Schlegel PN. Nonobstructive azoospermia: a revolutionary surgical approach and results. Semin Reprod Med. 2009;27(02):165–70.

    PubMed  Google Scholar 

  74. 74.

    Madureira C, Cunha M, Sousa M, Neto AP, Pinho MJ, Viana P, et al. Treatment by testicular sperm extraction and intracytoplasmic sperm injection of 65 azoospermic patients with non-mosaic Klinefelter syndrome with birth of 17 healthy children. Andrology. 2014;2(4):623–31. https://doi.org/10.1111/j.2047-2927.2014.00231.x.

    Article  PubMed  Google Scholar 

  75. 75.

    Fayomi AP, Peters K, Sukhwani M, Valli-Pulaski H. Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science. 2019;363(6433):1314–9. https://doi.org/10.1126/science.aav2914.

    Article  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Christiansen P, Andersson AM, Skakkebaek NE. Longitudinal studies of inhibin B levels in boys and young adults with Klinefelter syndrome. J Clin Endocrinol Metab. 2003;88(2):888–91. https://doi.org/10.1210/jc.2002-021379.

    Article  PubMed  Google Scholar 

  77. 77.

    Wikstrom AM, Painter JN, Raivio T, Aittomaki K, Dunkel L. Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome. Clin Endocrinol. 2010;65(1):92–7.

    Google Scholar 

  78. 78.

    María Gabriela B, Rey RA, Ignacio B, Patricia B, Luz A, Graciela DR, et al. Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome. Clin Endocrinol. 2010;67(6):863–70.

    Google Scholar 

  79. 79.

    Zeger MPD, Zinn AR, Lahlou N, Ramos P, Kowal K, Samango-Sprouse C, et al. Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome. J Pediatr. 2008;152(5):716–22.

    PubMed  Google Scholar 

  80. 80.

    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(4):998–1004. https://doi.org/10.1093/humrep/des002.

    Article  PubMed  Google Scholar 

  81. 81.

    Saen D, Van Gies I, Schepper J, De Tournaye H, Goossens E. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking? Hum Reprod. 2012;27(2):323–30.

    PubMed  Google Scholar 

  82. 82.

    Van SD, Vloeberghs V, Gies I, Mateizel I, Sermon K, De SJ, et al. When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome? Hum Reprod. 2018;33(6):1009–22.

    Google Scholar 

  83. 83.

    Vicdan K, Akarsu C, Sozen E, Buluc B, Vicdan A, Yilmaz Y, et al. Outcome of intracytoplasmic sperm injection using fresh and cryopreserved-thawed testicular spermatozoa in 83 azoospermic men with Klinefelter syndrome. J Obstet Gynaecol Res. 2016;42(11):1558–66. https://doi.org/10.1111/jog.13090.

    Article  PubMed  Google Scholar 

  84. 84.

    Kvist K, Thorup J, Byskov AG, Hoyer PE, Mollgard K, Yding Andersen C. Cryopreservation of intact testicular tissue from boys with cryptorchidism. Hum Reprod. 2006;21(2):484–91. https://doi.org/10.1093/humrep/dei331.

    Article  PubMed  Google Scholar 

  85. 85.

    Picton HM, Wyns C, Anderson RA, Goossens E, Jahnukainen K, Kliesch S, et al. A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. Hum Reprod. 2015;30(11):2463–75.

    PubMed  Google Scholar 

  86. 86.

    Baert Y, Braye A, Struijk RB, Pelt AMMV, Goossens E. Cryopreservation of testicular tissue before long-term testicular cell culture does not alter invitro cell dynamics. Fertil Steril. 2015;104(5):1244–52.e4.

    PubMed  Google Scholar 

  87. 87.

    Sá R, Cremades N, Malheiro I, Sousa M. Cryopreservation of human testicular diploid germ cell suspensions. Andrologia. 2012;44(6):366–72.

    PubMed  Google Scholar 

  88. 88.

    Tanaka A, Tanaka I, Nagayoshi M, Awata S, Himeno N, Kusunoki H. V-10: In vitro culture of the immature spermatogenic cells. Fertil Steril. 2006;86(3):S518–S9.

    Google Scholar 

  89. 89.

    Gianaroli L, Selman HA, Magli MC, Colpi G, Fortini D, Ferraretti AP. Birth of a healthy infant after conception with round spermatids isolated from cryopreserved testicular tissue. Fertil Steril. 1999;72(3):539–41. https://doi.org/10.1016/s0015-0282(99)00285-x.

    Article  PubMed  Google Scholar 

  90. 90.

    Ulug U, Bener F, Akman MA, Bahceci M. Partners of men with Klinefelter syndrome can benefit from assisted reproductive technologies. Fertil Steril. 2003;80(4):903–6.

    PubMed  Google Scholar 

  91. 91.

    Tanaka A, Nagayoshi M, Takemoto Y, Tanaka I, Kusunoki H, Watanabe S, et al. Fourteen babies born after round spermatid injection into human oocytes. Proc Natl Acad Sci U S A. 2015;112(47):14629–34. https://doi.org/10.1073/pnas.1517466112.

    Article  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Tanaka A, Suzuki K, Nagayoshi M, Tanaka A, Takemoto Y, Watanabe S, et al. Ninety babies born after round spermatid injection into oocytes: survey of their development from fertilization to 2 years of age. Fertil Steril. 2018;110(3):443–51. https://doi.org/10.1016/j.fertnstert.2018.04.033.

    Article  PubMed  Google Scholar 

  93. 93.

    Onofre J, Baert Y, Faes K, Goossens E. Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation. Hum Reprod Update. 2016;22(6):744–61.

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Friedler S, Raziel A, Strassburger D, Schachter M, Bern O, Ronel R. Outcome of ICSI using fresh and cryopreserved–thawed testicular spermatozoa in patients with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2001;16(12):2616–20.

    PubMed  Google Scholar 

  95. 95.

    Okada H, Goda K, Muto S, Maruyama O, Koshida M, Horie S. Four pregnancies in nonmosaic Klinefelter’s syndrome using cryopreserved-thawed testicular spermatozoa. Fertil Steril. 2005;84(5):1508.e13–6.

    Google Scholar 

  96. 96.

    Kyono K, Uto H, Nakajo Y, Kumagai S, Araki Y, Kanto S. Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm. J Assist Reprod Genet. 2007;24(1):47–51.

    PubMed  Google Scholar 

  97. 97.

    Fusi F, Calzi F, Rabellotti E, Papaleo E, Gonfiantini C, Bonzi V, et al. Fertilizing capability of frozen-thawed spermatozoa recovered from microsurgical epidydimal sperm aspiration and cryopreserved in oocyte-free human zona pellucida. Hum Reprod. 2001;16:117.

    Google Scholar 

  98. 98.

    Levi-Setti PE, Albani E, Negri L, Cesana A, Novara P, Bianchi S. Cryopreservation of a small number of spermatozoa in yolk-filled human zonae pellucidae. Arch Ital Urol Androl. 2003;75(4):195–8.

    PubMed  Google Scholar 

  99. 99.

    Alexander J, Irmhild G, Martina WB, Johann L, Andreas O, Heinz S. Novel method for the cryopreservation of testicular sperm and ejaculated spermatozoa from patients with severe oligospermia: A pilot study. Fertil Steril. 2004;82(2):445–7.

    Google Scholar 

  100. 100.

    Lecomte PJ, Barthelemy C, Nduwayo L, Hamamah S. Necrospermia: etiology and management. 1999.

  101. 101.

    Ortega C, Verheyen G, Raick D, Camus M, Devroey P, Tournaye H. Absolute asthenozoospermia and ICSI: what are the options? Hum Reprod Update. 2011;17(5):684–92. https://doi.org/10.1093/humupd/dmr018.

    Article  PubMed  Google Scholar 

  102. 102.

    Nordhoff V. How to select immotile but viable spermatozoa on the day of intracytoplasmic sperm injection? An embryologist's view. Andrology. 2015;3(2):156–62.

    PubMed  Google Scholar 

  103. 103.

    Esteves SC, Varghese AC. Laboratory handling of epididymal and testicular spermatozoa: what can be done to improve sperm injections outcome. J Human Reproduct Sci. 2012;5(3):233–43.

    Google Scholar 

  104. 104.

    Sallam H, Farrag A, Agameya A, Ezzeldin F, Eid A, Sallam A. The use of a modified hypo-osmotic swelling test for the selection of viable ejaculated and testicular immotile spermatozoa in ICSI. Hum Reprod. 2001;16(2):272–6.

    PubMed  Google Scholar 

  105. 105.

    Sallam HN, Ashraf F, Abdel-Fattah A, Yehia EG, Fathy E. The use of the modified hypo-osmotic swelling test for the selection of immotile testicular spermatozoa in patients treated with ICSI: a randomized controlled study. Hum Reprod. 2005;20(12):3435–40.

    PubMed  Google Scholar 

  106. 106.

    Westlander G, Barry M, Petrucco O, Norman R. Different fertilization rates between immotile testicular spermatozoa and immotile ejaculated spermatozoa for ICSI in men with Kartagener’s syndrome: case reports. Hum Reprod. 2003;18(6):1286–8.

    PubMed  Google Scholar 

  107. 107.

    Kordus RJ, Price RL, Davis JM, Whitman-Elia GF. Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: a case report. J Assist Reprod Genet. 2008;25(9-10):437–43.

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Geber S, Lemgruber M, Taitson PF, Valle M, Sampaio M. Birth of healthy twins after intracytoplasmic sperm injection using ejaculated immotile spermatozoa from a patient with Kartagener’s syndrome. Andrologia. 2012;44(s1):842–4.

    PubMed  Google Scholar 

  109. 109.

    Hossain A, Osuamkpe C, Hossain S, Phelps JY. Spontaneously developed tail swellings (SDTS) influence the accuracy of the hypo-osmotic swelling test (HOS-test) in determining membrane integrity and viability of human spermatozoa. J Assist Reprod Genet. 2010;27(2-3):83–6.

    PubMed  Google Scholar 

  110. 110.

    Griveau JF, Lobel B, Laurent MC, Michardière L, Lannou DL. Interest of pentoxifylline in ICSI with frozen–thawed testicular spermatozoa from patients with non-obstructive azoospermia. Reprod BioMed Online. 2006;12(1):14–8.

    PubMed  Google Scholar 

  111. 111.

    Vijay M, Ranjana M, Sucheta D, Kavita S, Sadhana D. Selection of viable spermatozoa from testicular biopsies: a comparative study between pentoxifylline and hypoosmotic swelling test. Fertil Steril. 2011;95(2):631–4.

    Google Scholar 

  112. 112.

    Kovacic B, Vlaisavljevic V, Reljic M. Clinical use of pentoxifylline for activation of immotile testicular sperm before ICSI in patients with azoospermia. J Androl. 2006;27(1):45–52. https://doi.org/10.2164/jandrol.05079.

    Article  PubMed  Google Scholar 

  113. 113.

    Terriou P, Hans E, Giorgetti C, Spach JL, Salzmann J, Urrutia V, et al. Pentoxifylline initiates motility in spontaneously immotile epididymal and testicular spermatozoa and allows normal fertilization, pregnancy, and birth after intracytoplasmic sperm injection. J Assist Reprod Genet. 2000;17(4):194–9.

    PubMed  PubMed Central  Google Scholar 

  114. 114.

    Unsal E, Turan V, Aktuna S, Hurdag C, Bereketoglu G, Canillioglu Y, et al. Effects of pentoxifylline and platelet activating factor on sperm DNA damage. Eur J Obstet Gynecol Reprod Biol. 2016;197:125–9. https://doi.org/10.1016/j.ejogrb.2015.12.016.

    Article  PubMed  Google Scholar 

  115. 115.

    Ain R, ., Seshagiri PB. Micromolar concentration of pentoxifylline improves development in vitro of hamster 8-cell embryos: confirmation of biological viability by embryo transfer. Reprod Fertil Dev 1997;9(7):697.

    PubMed  Google Scholar 

  116. 116.

    Aktan TM, Montag M, Duman S, Gorkemli H, Rink K, Yurdakul T. Use of a laser to detect viable but immotile spermatozoa. Andrologia. 2004;36(6):366–9. https://doi.org/10.1111/j.1439-0272.2004.00636.x.

    Article  PubMed  Google Scholar 

  117. 117.

    Nordhoff V, Schuring AN, Krallmann C, Zitzmann M, Schlatt S, Kiesel L, et al. Optimizing TESE-ICSI by laser-assisted selection of immotile spermatozoa and polarization microscopy for selection of oocytes. Andrology. 2013;1(1):67–74. https://doi.org/10.1111/j.2047-2927.2012.00020.x.

    Article  PubMed  Google Scholar 

  118. 118.

    Ogura A, Matsuda J, Yanagimachi R. Birth of normal young after electrofusion of mouse oocytes with round spermatids. Proc Natl Acad Sci U S A. 1994;91(16):7460–2.

    PubMed  PubMed Central  Google Scholar 

  119. 119.

    Ogura A, Matsuda J, Asano T, Suzuki O, Yanagimachi R. Mouse oocytes injected with cryopreserved round spermatids can develop into normal offspring. J Assist Reprod Genet. 1996;13(5):431–4.

    PubMed  Google Scholar 

  120. 120.

    Ogonuki N, Tsuchiya H, Hirose Y, Okada H, Ogura A, Sankai T. Pregnancy by the tubal transfer of embryos developed after injection of round spermatids into oocyte cytoplasm of the cynomolgus monkey (Macaca fascicularis). Hum Reprod. 2003;18(6):1273–80.

    PubMed  Google Scholar 

  121. 121.

    Ozil JP, Banrezes B, Toth S, Pan H, Schultz RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006;300(2):534–44. https://doi.org/10.1016/j.ydbio.2006.08.041.

    Article  PubMed  Google Scholar 

  122. 122.

    Sugaya S. Pregnancy following calcium ionophore oocyte activation in an oligozoospermia patient with repeated failure of fertilization after ICSI. Clin Exp Obstet Gynecol. 2010;37(4):261–2.

    PubMed  Google Scholar 

  123. 123.

    Nikiforaki D, Vanden Meerschaut F, de Roo C, Lu Y, Ferrer-Buitrago M, de Sutter P, et al. Effect of two assisted oocyte activation protocols used to overcome fertilization failure on the activation potential and calcium releasing pattern. Fertil Steril. 2016;105(3):798–806 e2. https://doi.org/10.1016/j.fertnstert.2015.11.007.

    Article  PubMed  Google Scholar 

  124. 124.

    Chen J, Qian Y, Tan Y, Mima H. Successful pregnancy following oocyte activation by strontium in normozoospermic patients of unexplained infertility with fertilisation failures during previous intracytoplasmic sperm injection treatment. Reprod Fertil Dev. 2010;22(5):852–5. https://doi.org/10.1071/RD09268.

    Article  PubMed  Google Scholar 

  125. 125.

    Kim JW, Kim SD, Yang SH, Yoon SH, Jung JH, Lim JH. Successful pregnancy after SrCl2 oocyte activation in couples with repeated low fertilization rates following calcium ionophore treatment. Syst Biol Reprod Med. 2014;60(3):177–82. https://doi.org/10.3109/19396368.2014.900832.

    Article  PubMed  Google Scholar 

  126. 126.

    Liu Y, Cao YX, Zhang ZG, Xing Q. Artificial oocyte activation and human failed-matured oocyte vitrification followed by in vitro maturation. Zygote. 2013;21(1):71–6. https://doi.org/10.1017/S0967199411000530.

    Article  PubMed  Google Scholar 

  127. 127.

    Baltaci V, Ayvaz OU, Unsal E, Aktas Y, Baltaci A, Turhan F, et al. The effectiveness of intracytoplasmic sperm injection combined with piezoelectric stimulation in infertile couples with total fertilization failure. Fertil Steril. 2010;94(3):900–4. https://doi.org/10.1016/j.fertnstert.2009.03.107.

    Article  PubMed  Google Scholar 

  128. 128.

    Mansour R, Fahmy I, Tawab NA, Kamal A, El-Demery Y, Aboulghar M, et al. Electrical activation of oocytes after intracytoplasmic sperm injection: a controlled randomized study. Fertil Steril. 2009;91(1):133–9. https://doi.org/10.1016/j.fertnstert.2007.08.017.

    Article  PubMed  Google Scholar 

  129. 129.

    Koo OJ, Jang G, Kwon DK, Kang JT, Kwon OS, Park HJ, et al. Electrical activation induces reactive oxygen species in porcine embryos. Theriogenology. 2008;70(7):1111–8. https://doi.org/10.1016/j.theriogenology.2008.06.031.

    Article  PubMed  Google Scholar 

  130. 130.

    Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485–7. https://doi.org/10.1016/S0140-6736(97)02174-0.

    Article  PubMed  Google Scholar 

  131. 131.

    Bischoff FZ, Hahn S, Johnson KL, Simpson JL, Bianchi DW, Lewis DE, et al. Intact fetal cells in maternal plasma: are they really there? Lancet. 2003;361(9352):139–40. https://doi.org/10.1016/S0140-6736(03)12191-5.

    Article  PubMed  Google Scholar 

  132. 132.

    Lo YM, Hjelm NM, Fidler C, Sargent IL, Murphy MF, Chamberlain PF, et al. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med. 1998;339(24):1734–8. https://doi.org/10.1056/NEJM199812103392402.

    Article  PubMed  Google Scholar 

  133. 133.

    Lo YM, Patel P, Sampietro M, Gillmer MD, Fleming KA, Wainscoat JS. Detection of single-copy fetal DNA sequence from maternal blood. Lancet. 1990;335(8703):1463–4.

    PubMed  Google Scholar 

  134. 134.

    Lo YD, Chiu RW. Non-invasive prenatal diagnosis of Down’s syndrome. Lancet. 2007;369(9578):1997. https://doi.org/10.1016/S0140-6736(07)60935-0.

    Article  PubMed  Google Scholar 

  135. 135.

    Hulten M. Non-invasive prenatal diagnosis of Down’s syndrome. Lancet. 2001;357(9260):963–4. https://doi.org/10.1016/S0140-6736(05)71670-6.

    Article  PubMed  Google Scholar 

  136. 136.

    Kou KO, Poon CF, Kwok SL, Chan KY, Tang MH, Kan AS, et al. Effect of non-invasive prenatal testing as a contingent approach on the indications for invasive prenatal diagnosis and prenatal detection rate of Down’s syndrome. Hong Kong Med J. 2016;22(3):223–30. https://doi.org/10.12809/hkmj154730.

    Article  PubMed  Google Scholar 

  137. 137.

    Perez-Carbajo E, Zapardiel I, Sanfrutos-Llorente L, Cruz-Melguizo S, Martinez-Payo C, Iglesias-Goy E. Prenatal diagnosis of concurrent achondroplasia and klinefelter syndrome. Case Rep Obstet Gynecol. 2015;2015:980749–2. https://doi.org/10.1155/2015/980749.

    Article  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Mansfield C, Hopfer S, Marteau TM. Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review. European Concerted Action: DADA (Decision-making After the Diagnosis of a fetal Abnormality). Prenat Diagn. 1999;19(9):808–12.

    PubMed  Google Scholar 

  139. 139.

    Pimpolari L, Liberati N, Martini M, Colloridi F, Radicioni A, Duse M, et al. Prenatal genetic counseling in Klinefelter syndrome: comments on the article by Lalatta et al. [2013] and a proposal of a new approach. Am J Med Genet A. 2015;167A(2):450–4. https://doi.org/10.1002/ajmg.a.36875.

    Article  PubMed  Google Scholar 

  140. 140.

    Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344(6268):768–70. https://doi.org/10.1038/344768a0.

    Article  PubMed  Google Scholar 

  141. 141.

    el-Hashemite N, Wells D, Delhanty JD. Preimplantation genetic diagnosis of beta-thalassaemia. Lancet. 1996;348(9027):620–1. https://doi.org/10.1016/s0140-6736(05)64841-6.

    Article  PubMed  Google Scholar 

  142. 142.

    Sermon K, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis. Lancet. 2004;363(9421):1633–41. https://doi.org/10.1016/S0140-6736(04)16209-0.

    Article  PubMed  Google Scholar 

  143. 143.

    Handyside AH, Pattinson JK, Penketh RJ, Delhanty JD, Winston RM, Tuddenham EG. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet. 1989;1(8634):347–9.

    PubMed  Google Scholar 

  144. 144.

    Schoolcraft WB, Fragouli E, Stevens J, Munne S, Katz-Jaffe MG, Wells D. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril. 2010;94(5):1700–6. https://doi.org/10.1016/j.fertnstert.2009.10.015.

    Article  PubMed  Google Scholar 

  145. 145.

    De Vos A, Staessen C, De Rycke M, Verpoest W, Haentjens P, Devroey P, et al. Impact of cleavage-stage embryo biopsy in view of PGD on human blastocyst implantation: a prospective cohort of single embryo transfers. Hum Reprod. 2009;24(12):2988–96. https://doi.org/10.1093/humrep/dep251.

    Article  PubMed  Google Scholar 

  146. 146.

    Gleicher N, Vidali A, Braverman J, Kushnir VA, Barad DH, Hudson C, et al. Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos. Reprod Biol Endocrinol. 2016;14(1):54. https://doi.org/10.1186/s12958-016-0193-6.

    Article  PubMed  PubMed Central  Google Scholar 

  147. 147.

    Palini S, Galluzzi L, De Stefani S, Bianchi M, Wells D, Magnani M, et al. Genomic DNA in human blastocoele fluid. Reprod BioMed Online. 2013;26(6):603–10. https://doi.org/10.1016/j.rbmo.2013.02.012.

    Article  PubMed  Google Scholar 

  148. 148.

    Wu H, Ding C, Shen X, Wang J, Li R, Cai B, et al. Medium-based noninvasive preimplantation genetic diagnosis for human alpha-thalassemias-SEA. Medicine. 2015;94(12):e669. https://doi.org/10.1097/MD.0000000000000669.

    Article  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Yang L, Lv Q, Chen W, Sun J, Wu Y, Wang Y, et al. resence of embryonic DNA in culture medium. Oncotarget. 2017;8(40):67805–9. https://doi.org/10.18632/oncotarget.18852.

    Article  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Xu J, Fang R, Chen L, Chen D, Xiao JP, Yang W, et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci U S A. 2016;113(42):11907–12. https://doi.org/10.1073/pnas.1613294113.

    Article  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Liu W, Zhang H, Hu D, Lu S, Sun X. The performance of MALBAC and MDA methods in the identification of concurrent mutations and aneuploidy screening to diagnose beta-thalassaemia disorders at the single- and multiple-cell levels. J Clin Lab Anal. 2018;32(2). https://doi.org/10.1002/jcla.22267.

  152. 152.

    Li W, Ma Y, Yu S, Sun N, Wang L, Chen D, et al. The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation. J Assist Reprod Genet. 2017;34(12):1653–8. https://doi.org/10.1007/s10815-017-1018-z.

    Article  PubMed  PubMed Central  Google Scholar 

  153. 153.

    Chiang CM, Lin CJ, Lee LM, Chen SM. Outcome of Intracytoplasmic Injection of Sperm Obtained by Testicular Sperm Extraction from 14 Azoospermic Men Suffering from 47,XXY Non-mosaic Klinefelter's Syndrome. Taiwanese J Obstet Gynecol. 2004;43:88–96. https://doi.org/10.1016/S1028-4559(09)60062-0.

  154. 154.

    Schiff JD, Palermo GD, Veeck LL, Marc G, Zev R, Schlegel PN. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90(11):6263–7.

  155. 155.

    Koga M, Tsujimura A, Takeyama M, Kiuchi H, Takao T, Miyagawa Y, et al. Clinical Comparison of Successful and Failed Microdissection Testicular Sperm Extraction in Patients with Nonmosaic Klinefelter Syndrome. Urology. 2007;70(2):341–5.

  156. 156.

    Ferhi K, Avakian R, Griveau JF, Guille F. Age as only predictive factor for successful sperm recovery in patients with Klinefelter's syndrome. Andrologia. 2009;41(2):84–7. https://doi.org/10.1111/j.1439-0272.2008.00875.x.

  157. 157.

    Yarali H, Polat M, Bozdag G, Gunel M, Alpas I, Esinler I, et al. TESE-ICSI in patients with non-mosaic Klinefelter syndrome: a comparative study. Reprod BioMed Online. 2009;18(6):756–60.

  158. 158.

    Bakircioglu ME, Ulug U, Erden HF, Tosun S, Bayram A, Ciray N, et al. Klinefelter syndrome: does it confer a bad prognosis in treatment of nonobstructive azoospermia? Fertil Steril. 2011;95(5):1696–9. https://doi.org/10.1016/j.fertnstert.2011.01.005.

  159. 159.

    Rives N, Milazzo JP, Perdrix A, Castanet M, Joly-Helas G, Sibert L, et al. The feasibility of fertility preservation in adolescents with Klinefelter syndrome. Hum Reprod. 2013;28(6):1468–79. https://doi.org/10.1093/humrep/det084.

  160. 160.

    Greco E, Scarselli F, Minasi MG, Casciani V, Zavaglia D, Dente D, et al. Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome. Hum Reprod 2013;28(5):1155–60.

  161. 161.

    Sabbaghian M, Modarresi T, Hosseinifar H, Hosseini J, Farrahi F, Dadkhah F, et al. Comparison of Sperm Retrieval and Intracytoplasmic Sperm Injection Outcome in Patients With and Without Klinefelter Syndrome. Urology. 2014;83(1):107–10. https://doi.org/10.1016/j.urology.2013.09.021.

  162. 162.

    Plotton I, d'Estaing SG, Cuzin B, Brosse A, Benchaib M, Lornage J, et al. Preliminary Results of a Prospective Study of Testicular Sperm Extraction in Young Versus Adult Patients With Nonmosaic 47, XXY Klinefelter Syndrome. J Clin Endocrin Metab. 2015;100(3):961–7. https://doi.org/10.1210/jc.2014-3083.

  163. 163.

    Majzoub A, Arafa M, Al Said S, Agarwal A, Seif A, Al Naimi A, et al. Outcome of testicular sperm extraction in nonmosaic Klinefelter syndrome patients: what is the best approach? Andrologia. 2016;48(2):171–6. https://doi.org/10.1111/and.12428.

  164. 164.

    Chihara M, Ogi K, Ishiguro T, Yoshida K, Godo C, Takakuwa K, et al. Microdissection testicular sperm extraction in five Japanese patients with nonmosaic Klinefelter's syndrome. Reproduc Med Biol. 2018;17(2):209–16.

  165. 165.

    Ozer C, Caglar AP, Goren MR, Toksoz S, Gul U, Turunc T. Sperm retrieval by microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in nonobstructive azoospermic patients with Klinefelter syndrome. Andrologia. 2018;50(3):e12983.

Download references

Acknowledgments

The authors thank all members of the IVF center in Shanghai General hospital for helpful discussions when preparing this manuscript.

Authors’roles

C.W, B. M, and Y. Y collected the information, analyzed the data, and wrote the manuscript. S. D, Y. Y, and S. J designed the pictures. Z. Z supervised the conception, design, and development of all aspects of the article and was involved in the data analysis and manuscript preparation. W. S, W. Y, F.Y, W.Y, and Z. Z review and editing of the final article. All the authors have seen and approved the final version.

Funding

This work was supported by grants from the National Natural Science Foundation of China (grants 81672562, 81872111, 81370074, 81902630), National Key Technology R&D Program of China (2019YFC1005200 and 2019YFC1005201), Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan (19XD1423100), the project of Outstanding Medical Doctor for ZZ, the cross project of Medical and Engineering (YG2016MS27), Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20181714), the projects sponsored by the development fund for Shanghai talents, the Shanghai Municipal Public Health Bureau (grant XYQ2013119), and the “Chenxing Project” from Shanghai Jiao Tong University to Z.Z.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Zhenbo Zhang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, W., Bai, M.Z., Yang, Y. et al. ART strategies in Klinefelter syndrome. J Assist Reprod Genet (2020). https://doi.org/10.1007/s10815-020-01818-2

Download citation

Keywords

  • Klinefelter syndrome
  • Administration strategy
  • Single sperm cryopreservation
  • TESE
  • Fertility preservation