Semin Reprod Med 2009; 27(2): 137-148
DOI: 10.1055/s-0029-1202302
© Thieme Medical Publishers

Reproduction in Men with Klinefelter Syndrome: The Past, the Present, and the Future

Darius A. Paduch1 , 2 , Alexander Bolyakov1 , Paula Cohen3 , Alexander Travis4
  • 1Department of Urology and Reproductive Medicine, Weill Medical College of Cornell University, New York, New York
  • 2Center for Biomedical Research, Population Council, New York, New York
  • 3Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York
  • 4Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, New York
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
26. Februar 2009 (online)

ABSTRACT

Klinefelter syndrome (KS) is the most common chromosomal aberration in men. There are approximately 250,000 men with KS in the United States, and the prevalence of KS in male reproductive practices is 3 to 4%; however, most men are never diagnosed. KS has an effect on normal development, growth, social interactions, bone structure, and sexual and reproductive function, thus a multidisciplinary approach to men with KS is important in providing state of the art care to children and men with KS.

Over the last 10 years, with advancements in artificial reproductive techniques and the successful delivery of healthy children from men with KS, the involvement of reproductive endocrinologists and urologists in the care of patients with KS is becoming commonplace. The new areas of intense research investigate optimal methods of hormonal manipulations, preservation of fertility in adolescents, and development of universal early screening programs for KS.

This review provides the latest update in our understanding of the pathophysiology, natural history, and evolving paradigms of therapy in adolescents and men with KS.

REFERENCES

  • 1 Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter's syndrome.  Lancet. 2004;  364 273-283
  • 2 Graham Jr J M, Bashir A S, Stark R E, Silbert A, Walzer S. Oral and written language abilities of XXY boys: implications for anticipatory guidance.  Pediatrics. 1988;  81 795-806
  • 3 Samango-Sprouse C. Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation.  Semin Reprod Med. 2001;  19 193-202
  • 4 Tournaye H, Staessen C, Liebaers I et al.. Testicular sperm recovery in nine 47,XXY Klinefelter patients.  Hum Reprod. 1996;  11 1644-1649
  • 5 Palermo G D, Schlegel P N, Sills E 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;  338 588-590
  • 6 Thomas N S, Hassold T J. Aberrant recombination and the origin of Klinefelter syndrome.  Hum Reprod Update. 2003;  9 309-317
  • 7 Lowe X, Eskenazi B, Nelson D O et al.. Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome.  Am J Hum Genet. 2001;  69 1046-1054
  • 8 Palermo G D, Neri Q V, Hariprashad J J et al.. ICSI and its outcome.  Semin Reprod Med. 2000;  18 161-169
  • 9 Hong Y K, Ontiveros S D, Strauss W M. A revision of the human XIST gene organization and structural comparison with mouse Xist.  Mamm Genome. 2000;  11 220-224
  • 10 Nguyen D K, Disteche C M. Dosage compensation of the active X chromosome in mammals.  Nat Genet. 2006;  38 47-53
  • 11 Nguyen D K, Disteche C M. High expression of the mammalian X chromosome in brain.  Brain Res. 2006;  1126 46-49
  • 12 Vawter M P, Harvey P D, DeLisi L E. Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.  Am J Med Genet B Neuropsychiatr Genet. 2007;  144B 728-734
  • 13 Ross M T, Grafham D V, Coffey A J et al.. The DNA sequence of the human X chromosome.  Nature. 2005;  434 325-337
  • 14 Akhtar A. Dosage compensation: an intertwined world of RNA and chromatin remodelling.  Curr Opin Genet Dev. 2003;  13 161-169
  • 15 Zechner U, Wilda M, Kehrer-Sawatzki H et al.. A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution?.  Trends Genet. 2001;  17 697-701
  • 16 Wilda M, Bachner D, Zechner U et al.. Do the constraints of human speciation cause expression of the same set of genes in brain, testis, and placenta?.  Cytogenet Cell Genet. 2000;  91 300-302
  • 17 Khil P P, Smirnova N A, Romanienko P J, Camerini-Otero R D. The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation.  Nat Genet. 2004;  36 642-646
  • 18 Wang P J, McCarrey J R, Yang F, Page D C. An abundance of X-linked genes expressed in spermatogonia.  Nat Genet. 2001;  27 422-426
  • 19 Schiff J D, Palermo G D, Veeck L L et al.. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome.  J Clin Endocrinol Metab. 2005;  90 6263-6267
  • 20 Damani M N, Mittal R, Oates R D. Testicular tissue extraction in a young male with 47,XXY Klinefelter's syndrome: potential strategy for preservation of fertility.  Fertil Steril. 2001;  76 1054-1056
  • 21 Aksglaede L, Wikstrom A M, Rajpert-De Meyts E et al.. Natural history of seminiferous tubule degeneration in Klinefelter syndrome.  Hum Reprod Update. 2006;  12 39-48
  • 22 Lin Y M, Huang W J, Lin J S, Kuo P L. Progressive depletion of germ cells in a man with nonmosaic Klinefelter's syndrome: optimal time for sperm recovery.  Urology. 2004;  63 380-381
  • 23 Yamamoto Y, Sofikitis N, Mio Y et al.. Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelter's syndrome.  Hum Reprod. 2002;  17 886-896
  • 24 Wikstrom A M, Raivio T, Hadziselimovic F et al.. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion.  J Clin Endocrinol Metab. 2004;  89 2263-2270
  • 25 Bastida M G, Rey R A, Bergada I et al.. Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome.  Clin Endocrinol (Oxf). 2007;  67 863-870
  • 26 Wikstrom A M, Bay K, Hero M, Andersson A M, Dunkel L. Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome.  J Clin Endocrinol Metab. 2006;  91 4705-4708
  • 27 Regadera J, Codesal J, Paniagua R, Gonzalez-Peramato P, Nistal M. Immunohistochemical and quantitative study of interstitial and intratubular Leydig cells in normal men, cryptorchidism, and Klinefelter's syndrome.  J Pathol. 1991;  164 299-306
  • 28 Boujrad N, Hochereau-de Reviers M T, Carreau S. Evidence for germ cell control of Sertoli cell function in three models of germ cell depletion in adult rat.  Biol Reprod. 1995;  53 1345-1352
  • 29 Hsueh W A, Hsu T H, Federman D D. Endocrine features of Klinefelter's syndrome.  Medicine (Baltimore). 1978;  57 447-461
  • 30 Raman J D, Schlegel P N. Aromatase inhibitors for male infertility.  J Urol. 2002;  167(2 Pt 1) 624-629
  • 31 Wikstrom A M, Hoei-Hansen C E, Dunkel L, Rajpert-De Meyts E. 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. 2007;  92 714-719
  • 32 Morel F, Bernicot I, Herry A et al.. An increased incidence of autosomal aneuploidies in spermatozoa from a patient with Klinefelter's syndrome.  Fertil Steril. 2003;  79(Suppl 3) 1644-1646
  • 33 Eskenazi B, Wyrobek A J, Kidd S A et al.. Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome.  Hum Reprod. 2002;  17 576-583
  • 34 Bergere M, Wainer R, Nataf V et al.. Biopsied testis cells of four 47,XXY patients: fluorescence in-situ hybridization and ICSI results.  Hum Reprod. 2002;  17 32-37
  • 35 Paduch D A. FastStart High Fidelity PCR system simplifies study of epigenetics and DNA methylation.  Biochemica (Indianap, Ind). 2005;  2 19
  • 36 Mantovani V, Dondi E, Larizza D et al.. Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?.  Eur J Hum Genet. 2002;  10 137-140
  • 37 Samli H, Samli M M, Azgoz A, Solak M. Y chromosome microdeletion in a case with Klinefelter's syndrome.  Arch Androl. 2006;  52 427-431
  • 38 Mitra A, Dada R, Kumar R et al.. Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.  Asian J Androl. 2006;  8 81-88
  • 39 Campbell W A, Price W H. Venous thromboembolic disease in Klinefelter's syndrome.  Clin Genet. 1981;  19 275-280
  • 40 Vetto J, Jun S Y, Paduch D, Eppich H, Shih R. Stages at presentation, prognostic factors, and outcome of breast cancer in males.  Am J Surg. 1999;  177 379-383
  • 41 Swerdlow A J, Schoemaker M J, Higgins C D, Wright A F, Jacobs P A. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study.  J Natl Cancer Inst. 2005;  97 1204-1210
  • 42 Friedler S, Raziel A, Strassburger D et al.. Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter's syndrome.  Hum Reprod. 2001;  16 2616-2620
  • 43 Greco E, Iacobelli M, Rienzi L et al.. Birth of a healthy boy after fertilization of cryopreserved oocytes with cryopreserved testicular spermatozoa from a man with nonmosaic Klinefelter syndrome.  Fertil Steril. 2008;  89 991-992
  • 44 Faglia G, Arosio M, Porretti S. Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?.  J Endocrinol Invest. 2000;  23 721-723
  • 45 Vigueras-Villasenor R M, Moreno-Mendoza N A, Reyes-Torres G et al.. The effect of estrogen on testicular gonocyte maturation.  Reprod Toxicol. 2006;  22 513-520
  • 46 Kuhn J M, Reznik Y, Mahoudeau J A et al.. hCG test in gynaecomastia: further study.  Clin Endocrinol (Oxf). 1989;  31 581-590
  • 47 Sibert L, Rives N, Rey D, Mac E B, Grise P. Semen cryopreservation after orchidectomy in men with testicular cancer.  BJU Int. 1999;  84 1038-1042
  • 48 Tournaye H, Goossens E, Verheyen G et al.. Preserving the reproductive potential of men and boys with cancer: current concepts and future prospects.  Hum Reprod Update. 2004;  10 525-532
  • 49 Krausz C, Forti G. Sperm cryopreservation in male infertility due to genetic disorders.  Cell Tissue Bank. 2006;  7 105-112
  • 50 Kinsey A C, Pomeroy W R, Martin C E. Sexual behavior in the human male. 1948.  Am J Public Health. 2003;  93 894-898
  • 51 Paduch D A, Niedzielski J. Semen analysis in young men with varicocele: preliminary study.  J Urol. 1996;  156(2 Pt 2) 788-790
  • 52 van den Berg H, Repping S, van der Veen F. Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer.  Hum Reprod. 2007;  22 594-597

Darius A PaduchM.D. Ph.D. 

Department of Urology, Weill Medical College of Cornell University

525 East 68th St., F-924A, New York, NY 10065

eMail: darius.paduch@mac.com