{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:57:32Z","timestamp":1768348652328,"version":"3.49.0"},"reference-count":239,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Foundation for Science and Technology (FCT) Portugal","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"the Foundation for Science and Technology (FCT) Portugal","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"the Foundation for Science and Technology (FCT) Portugal","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"ITR (Laboratory for Integrative and Translational Research in Population Health)","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"ITR (Laboratory for Integrative and Translational Research in Population Health)","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"ITR (Laboratory for Integrative and Translational Research in Population Health)","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500\/1000 per male live birth (karyotype 47,XXY). High stature, tiny testicles, small penis, gynecomastia, feminine body proportions and hair, visceral obesity, and testicular failure are all symptoms of KS. Endocrine (osteoporosis, obesity, diabetes), musculoskeletal, cardiovascular, autoimmune disorders, cancer, neurocognitive disabilities, and infertility are also outcomes of KS. Causal theories are discussed in addition to hormonal characteristics and testicular histology. The retrieval of spermatozoa from the testicles for subsequent use in assisted reproduction treatments is discussed in the final sections. Despite testicular atrophy, reproductive treatments allow excellent results, with rates of 40\u201360% of spermatozoa recovery, 60% of clinical pregnancy, and 50% of newborns. This is followed by a review on the predictive factors for successful sperm retrieval. The risks of passing on the genetic defect to children are also discussed. Although the risk is low (0.63%) when compared to the general population (0.5\u20131%), patients should be informed about embryo selection through pre-implantation genetic testing (avoids clinical termination of pregnancy). Finally, readers are directed to a number of reviews where they can enhance their understanding of comprehensive diagnosis, clinical care, and fertility preservation.<\/jats:p>","DOI":"10.3390\/genes14030647","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T05:18:43Z","timestamp":1678079923000},"page":"647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-3822","authenticated-orcid":false,"given":"Ros\u00e1lia","family":"S\u00e1","sequence":"first","affiliation":[{"name":"Laboratory of Cell Biology, Department of Microscopy, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"UMIB-Unit for Multidisciplinary Research in Biomedicine, 4050-313 Porto, Portugal"},{"name":"ITR-Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda do Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Department of Urology, Hospital Eduardo Santos Silva, Centro Hospitalar de Vila Nova de Gaia\/Espinho, Rua Concei\u00e7\u00e3o Fernandes, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"Alberto","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Medicine, University of Porto, Alameda do Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Centre for Reproductive Genetics A. Barros, Av. do Bessa, 240, 1\u00ba Dto. Frente, 4100-012 Porto, Portugal"},{"name":"Institute of Health Research and Innovation (IPATIMUP\/i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-3290","authenticated-orcid":false,"given":"M\u00e1rio","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Department of Microscopy, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"UMIB-Unit for Multidisciplinary Research in Biomedicine, 4050-313 Porto, Portugal"},{"name":"ITR-Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1210\/jcem-2-11-615","article-title":"Syndrome characterized by gynecomastia, aspermatogenesis without A-Leydigism, and increased excretion of follicle stimulating hormone","volume":"2","author":"Klinefelter","year":"1942","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/183302a0","article-title":"A case of human intersexuality having a possible XXY sex-determining mechanism","volume":"183","author":"Jacobs","year":"1959","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","article-title":"Klinefelter syndrome","volume":"364","author":"Lanfranco","year":"2004","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","article-title":"Klinefelter syndrome (KS): Genetics, Clinical phenotype and hypogonadism","volume":"40","author":"Bonomi","year":"2017","journal-title":"J. Endocrinol. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/rmb2.12261","article-title":"Klinefelter syndrome: From pediatrics to geriatrics","volume":"18","author":"Shiraishi","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"ref_6","first-page":"561","article-title":"Klinefelter Syndrome","volume":"Volume 5","author":"Huhtaniemi","year":"2019","journal-title":"Encyclopedia of Endocrine Diseases"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.beem.2020.101480","article-title":"Infertility considerations in klinefelter syndrome: From origin to management","volume":"34","author":"Deebel","year":"2020","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/humupd\/dmi039","article-title":"Natural history of seminiferous tubule degeneration in Klinefelter syndrome","volume":"12","author":"Aksglaede","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1093\/humrep\/dep431","article-title":"Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?","volume":"25","author":"Fullerton","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/molehr\/gaq019","article-title":"Novel genetic aspects of Klinefelter\u2019s syndrome","volume":"16","author":"Gromoll","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1093\/humrep\/der193","article-title":"Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter syndrome","volume":"26","author":"Gruchy","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2164\/jandrol.110.011536","article-title":"Further evidence of the clinical, hormonal, and genetic heterogeneity of Klinefelter syndrome: A study of 216 infertile Egyptian patients","volume":"33","author":"Elsobky","year":"2012","journal-title":"J. Androl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1210\/jc.2002-021491","article-title":"Prenatal and postnatal prevalence of Klinefelter syndrome: A national registry study","volume":"88","author":"Bojesen","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1210\/er.2017-00212","article-title":"Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology","volume":"39","author":"Gravholt","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1001\/archinte.158.12.1309","article-title":"Klinefelter syndrome","volume":"158","author":"Smyth","year":"1998","journal-title":"Arch. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/01.GIM.0000095626.54201.D0","article-title":"Klinefelter syndrome: Expanding the phenotype and identifying new research directions","volume":"5","author":"Simpson","year":"2003","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/EJE-12-0934","article-title":"Testicular function and fertility in men with Klinefelter syndrome: A review","volume":"168","author":"Aksglaede","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/andr.12208","article-title":"The Klinefelter syndrome: Current management and research challenges","volume":"4","author":"Nieschlag","year":"2016","journal-title":"Andrology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/j.1651-2227.2011.02246.x","article-title":"Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: A Copenhagen experience","volume":"100","author":"Aksglaede","year":"2011","journal-title":"Acta Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0022-4731(84)90203-6","article-title":"Hormonal regulation of androgen production by the Leydig cell","volume":"20","author":"Dufau","year":"1984","journal-title":"J. Steroid Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e28138","DOI":"10.4161\/spmg.28138","article-title":"Receptors and signaling pathways involved in proliferation and differentiation of Sertoli cells","volume":"4","author":"Lucas","year":"2014","journal-title":"Spermatogenesis"},{"key":"ref_22","first-page":"468","article-title":"A short evolutionary history of FSH-stimulated spermatogenesis","volume":"14","author":"Huhtaniemi","year":"2015","journal-title":"Hormones"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ucl.2016.01.001","article-title":"Physiology of the Hypothalamic Pituitary Gonadal Axis in the Male","volume":"43","author":"Corradi","year":"2016","journal-title":"Urol. Clin. N. Am."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1210\/jc.2012-2382","article-title":"Klinefelter syndrome-a clinical update","volume":"98","author":"Groth","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1210\/jc.2005-0697","article-title":"Morbidity in Klinefelter syndrome: A Danish register study based on hospital discharge diagnoses","volume":"91","author":"Bojesen","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1093\/molehr\/gaq016","article-title":"Klinefelter\u2019s syndrome, type 2 diabetes and the metabolic syndrome: The impact of body composition","volume":"16","author":"Bojesen","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.beem.2010.09.006","article-title":"Klinefelter syndrome","volume":"25","author":"Dunkel","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E508","DOI":"10.1210\/jc.2014-2834","article-title":"Anthropometry in Klinefelter syndrome\u2014Multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism","volume":"100","author":"Chang","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.2047-2927.2014.00231.x","article-title":"Treatment by testicular sperm extraction and intracytoplasmic sperm injection of 65 azoospermic patients with non-mosaic Klinefelter syndrome with birth of 17 healthy children","volume":"2","author":"Madureira","year":"2014","journal-title":"Andrology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/ajmg.c.31786","article-title":"Gonadal dysfunction and beyond: Clinical challenges in children, adolescents, and adults with 47,XXY Klinefelter syndrome","volume":"184","author":"Zitzmann","year":"2020","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_31","first-page":"412","article-title":"Clinical outcomes of 77 TESE treatment cycles in non-mosaic Klinefelter syndrome patients","volume":"26","author":"Barros","year":"2022","journal-title":"JBRA Assist. Reprod."},{"key":"ref_32","first-page":"39","article-title":"Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome","volume":"64","author":"Ross","year":"2005","journal-title":"Horm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E746","DOI":"10.1210\/jc.2010-2103","article-title":"Assessment of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome: Insulin-like peptide 3 levels are normal and positively correlated with LH levels","volume":"96","author":"Cabrol","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/j.1651-2227.2011.02280.x","article-title":"Clinical and hormonal status of infants with nonmosaic XXY karyotype","volume":"100","author":"Lahlou","year":"2011","journal-title":"Acta Paediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ajmg.c.31794","article-title":"Minipuberty in Klinefelter syndrome: Current status and future directions","volume":"184","author":"Aksglaede","year":"2020","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.jpeds.2007.10.019","article-title":"Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome","volume":"152","author":"Zeger","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/ajmg.c.31807","article-title":"Early neurodevelopmental and medical profile in children with sex chromosome trisomies: Background for the prospective eXtraordinarY babies study to identify early risk factors and targets for intervention","volume":"184","author":"Tartaglia","year":"2020","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.1210\/jc.2005-0432","article-title":"Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome","volume":"90","author":"Zinn","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1172-1-42","article-title":"Klinefelter syndrome and other sex chromosomal aneuploidies","volume":"1","author":"Visootsak","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_40","first-page":"150","article-title":"Genital anomalies in Klinefelter\u2019s syndrome","volume":"68","author":"Lee","year":"2007","journal-title":"Horm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1210\/js.2019-00274","article-title":"Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition","volume":"3","author":"Davis","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1515\/jpem-2019-0243","article-title":"Sex differences in infant body composition emerge in the first 5 months of life","volume":"32","author":"Davis","year":"2019","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1210\/jc.2007-1426","article-title":"Abnormal sex chromosome constitution and longitudinal growth: Serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome (SRY)-positive 46,XX karyotypes","volume":"93","author":"Aksglaede","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_44","first-page":"2259","article-title":"Klinefelter syndrome","volume":"72","author":"Wattendorf","year":"2005","journal-title":"Am. Fam. Physician"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/S0028-3932(03)00061-7","article-title":"Executive skills in Klinefelter\u2019s syndrome","volume":"41","author":"Temple","year":"2003","journal-title":"Neuropsychologia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/1098-2779(2000)6:2<107::AID-MRDD4>3.0.CO;2-2","article-title":"Neurobehavioral phenotype of Klinefelter syndrome","volume":"6","author":"Geschwind","year":"2000","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4103\/1008-682X.122201","article-title":"The role of hypogonadism in Klinefelter syndrome","volume":"16","author":"Groth","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/andr.12909","article-title":"European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology","volume":"9","author":"Zitzmann","year":"2021","journal-title":"Andrology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2337\/dc06-0145","article-title":"The metabolic syndrome is frequent in Klinefelter\u2019s syndrome and is associated with abdominal obesity and hypogonadism","volume":"29","author":"Bojesen","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/ncpuro0775","article-title":"Klinefelter syndrome in clinical practice","volume":"4","author":"Bojesen","year":"2007","journal-title":"Nat. Clin. Pract. Urol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"112","DOI":"10.12688\/f1000research.16747.1","article-title":"Recent advances in managing and understanding Klinefelter syndrome","volume":"8","author":"Bearelly","year":"2019","journal-title":"F1000Research"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/ajmg.c.31798","article-title":"Morbidity in Klinefelter syndrome and the effect of testosterone treatment","volume":"184","author":"Chang","year":"2020","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e000271","DOI":"10.1161\/JAHA.113.000271","article-title":"Testosterone and the cardiovascular system: A comprehensive review of the basic science literature","volume":"2","author":"Herring","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s12276-020-0397-x","article-title":"Therapeutics targeting the fibrinolytic system","volume":"52","author":"Lin","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100064","DOI":"10.1016\/j.cytox.2022.100064","article-title":"Plasminogen activator inhibitor-1 mediate downregulation of adiponectin in type 2 diabetes patients with metabolic syndrome","volume":"4","author":"Nawaz","year":"2022","journal-title":"Cytokine X"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/MED.0000000000000454","article-title":"Endocrine aspects of Klinefelter syndrome","volume":"26","author":"Lizarazo","year":"2019","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1586\/erm.10.63","article-title":"Klinefelter syndrome: Clinical and molecular aspects","volume":"10","author":"Giltay","year":"2010","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jpsychires.2013.10.001","article-title":"Klinefelter syndrome and risk of psychosis, autism and ADHD","volume":"48","author":"Larsson","year":"2014","journal-title":"J. Psychiatr. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/1871530318666180703160250","article-title":"Neuropsychiatric Aspects in Men with Klinefelter Syndrome","volume":"19","author":"Giagulli","year":"2019","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.fertnstert.2012.06.019","article-title":"The genetic origin of Klinefelter syndrome and its effect on spermatogenesis","volume":"98","author":"Maiburg","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/humupd\/dmg028","article-title":"Aberrant recombination and the origin of Klinefelter syndrome","volume":"9","author":"Thomas","year":"2003","journal-title":"Hum. Reprod. Update"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1210\/jc.2004-1424","article-title":"X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients","volume":"89","author":"Zitzmann","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e642","DOI":"10.1111\/j.1365-2605.2011.01223.x","article-title":"Genotype and phenotype in Klinefelter syndrome\u2014impact of androgen receptor polymorphism and skewed X inactivation","volume":"34","author":"Bojesen","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.fertnstert.2013.12.051","article-title":"Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients","volume":"101","author":"Samplaski","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E518","DOI":"10.1210\/jc.2014-2780","article-title":"Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome","volume":"100","author":"Zitzmann","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/ajmg.a.33334","article-title":"Increased number of sex chromosomes affects height in a nonlinear fashion: A study of 305 patients with sex chromosome aneuploidy","volume":"152A","author":"Ottesen","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1093\/hmg\/ddr030","article-title":"FGFR3 is a target of the homeobox transcription factor SHOX in limb development","volume":"20","author":"Decker","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/andr.12146","article-title":"The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype","volume":"4","author":"Rocca","year":"2016","journal-title":"Andrology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13740","DOI":"10.1038\/s41598-018-31780-0","article-title":"DNA hypermethylation and differential gene expression associated with Klinefelter syndrome","volume":"8","author":"Nielsen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1046\/j.1365-2605.2003.00393.x","article-title":"The CAG repeat polymorphism within the androgen receptor gene and maleness","volume":"26","author":"Zitzmann","year":"2003","journal-title":"Int. J. Androl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/17446651.2019.1671821","article-title":"Fertility management of Klinefelter syndrome","volume":"14","author":"Fainberg","year":"2019","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1365-2265.2006.02554.x","article-title":"Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome","volume":"65","author":"Painter","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/ejhg.2014.142","article-title":"The FSHB- 211G>T variant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome","volume":"23","author":"Busch","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(04)16256-9","article-title":"Genomic imprinting in disruptive spermatogenesis","volume":"363","author":"Marques","year":"2004","journal-title":"Lancet"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/molehr\/gam093","article-title":"Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia","volume":"14","author":"Marques","year":"2008","journal-title":"Mol. Hum. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.4161\/epi.6.11.17993","article-title":"DNA methylation imprinting marks and DNA methyltransferase expression in human spermatogenic cell stages","volume":"6","author":"Marques","year":"2011","journal-title":"Epigenetics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/andr.12379","article-title":"Impairment of sperm DNA methylation in male infertility: A meta-analytic study","volume":"5","author":"Santi","year":"2017","journal-title":"Andrology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13148-019-0720-3","article-title":"High-resolution analysis of germ cells from men with sex chromosomal aneuploidies reveals normal transcriptome but impaired imprinting","volume":"11","author":"Laurentino","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/11.suppl_4.1","article-title":"Cytogenetics of infertile men","volume":"11","author":"Bonduelle","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/j.1939-4640.2002.tb02597.x","article-title":"Cytogenetic investigations of infertile men with low sperm counts: A 25-year experience","volume":"23","author":"Vincent","year":"2002","journal-title":"J. Androl."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.reprotox.2006.04.016","article-title":"Genetic causes of male infertility","volume":"22","author":"Ferlin","year":"2006","journal-title":"Reprod. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/molehr\/gaq022","article-title":"Clinical and therapeutic aspects of Klinefelter\u2019s syndrome: Sexual function","volume":"16","author":"Vignozzi","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1093\/humrep\/der351","article-title":"Hidden mosaicism in patients with Klinefelter\u2019s syndrome: Implications for genetic reproductive counselling","volume":"26","author":"Blanco","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S0140-6736(63)92413-9","article-title":"Possible fertility in Klinefelter\u2019s syndrome","volume":"1","author":"Kaplan","year":"1963","journal-title":"Lancet"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1530\/jrf.0.0250401","article-title":"A study of four cases with Klinefelter\u2019s syndrome, showing motile spermatozoa in their ejaculates","volume":"25","author":"Foss","year":"1971","journal-title":"J. Reprod. Fertil."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/j.1939-4640.2003.tb02638.x","article-title":"Clinical and diagnostic features of patients with suspected Klinefelter syndrome","volume":"24","author":"Kamischke","year":"2003","journal-title":"J. Androl."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/BF03350343","article-title":"Spermatogenesis in Klinefelter syndrome","volume":"33","author":"Selice","year":"2010","journal-title":"J. Endocrinol. Investig."},{"key":"ref_88","first-page":"42","article-title":"Nonmosaic Klinefelter Syndrome Successful Conception after TESE\/ICSI: A case report","volume":"1","author":"SayedElAkhras","year":"2018","journal-title":"Open Access J. Reprod. Syst. Sex. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.jpurol.2021.02.021","article-title":"Androgenization in Klinefelter syndrome: Clinical spectrum from infancy through young adulthood","volume":"17","author":"Nassau","year":"2021","journal-title":"J. Pediatr. Urol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/andr.12767","article-title":"Sperm retrieval rates in non-mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real-life setting?","volume":"8","author":"Boeri","year":"2020","journal-title":"Andrology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/223643a0","article-title":"Two types of tubules containing only Sertoli cells in adults with Klinefelter\u2019s syndrome","volume":"223","author":"Skakkebaek","year":"1969","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1511.e1","DOI":"10.1016\/j.fertnstert.2005.10.069","article-title":"Adult onset of declining spermatogenesis in a man with nonmosaic Klinefelter\u2019s syndrome","volume":"85","author":"Ichioka","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.fertnstert.2011.11.009","article-title":"Presence of spermatogonia in 47,XXY men with no spermatozoa recovered after testicular sperm extraction","volume":"97","author":"Tournaye","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/S0015-0282(01)01793-9","article-title":"Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: A prospective study of possible predictive factors for successful sperm recovery","volume":"75","author":"Westlander","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/humrep\/17.1.32","article-title":"Biopsied testis cells of four 47,XXY patients: Fluorescence in-situ hybridization and ICSI results","volume":"17","author":"Wainer","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_96","first-page":"12","article-title":"A fertile patient with Klinefelter\u2019s syndrome","volume":"43","author":"Warburg","year":"1963","journal-title":"Acta Endocrinol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/BF00218909","article-title":"Achievement of meiosis in XXY germ cells: Study of 543 sperm karyotypes from an XY\/XXY mosaic patient","volume":"93","author":"Cozzi","year":"1994","journal-title":"Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/BF02265260","article-title":"Increased incidence of hyperhaploid 24,XY spermatozoa detected by three-colour FISH in a 46,XY\/47,XXY male","volume":"97","author":"Chevret","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_99","first-page":"203","article-title":"High incidence of sperm sex chromosomes aneuploidies in two patients with Klinefelter\u2019s syndrome","volume":"83","author":"Foresta","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/humrep\/16.5.887","article-title":"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","volume":"16","author":"Blanco","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_101","first-page":"3807","article-title":"Analysis of meiosis in intratesticular germ cells from subjects affected by classic Klinefelter\u2019s syndrome","volume":"84","author":"Foresta","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1093\/humrep\/dep180","article-title":"Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients","volume":"24","author":"Sciurano","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/humrep\/17.4.886","article-title":"Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelter\u2019s syndrome","volume":"17","author":"Yamamoto","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1530\/rep.1.00641","article-title":"Recombination in men with Klinefelter syndrome","volume":"130","author":"Gonsalves","year":"2005","journal-title":"Reproduction"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S0015-0282(00)01556-9","article-title":"Sperm chromosome analysis and outcome of IVF in patients with non-mosaic Klinefelter\u2019s syndrome","volume":"74","author":"Levron","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0015-0282(16)57315-4","article-title":"High fertilization rate with intracytoplasmic sperm injection in mosaic Klinefelter\u2019s syndrome","volume":"63","author":"Harari","year":"1995","journal-title":"Fertil. Steril."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1177\/0300060518788757","article-title":"Intracytoplasmic sperm injection outcome of ejaculated spermatozoa from a man with mosaic Klinefelter\u2019s Syndrome: Case report and literature review","volume":"46","author":"Yu","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/humrep\/15.2.440","article-title":"Fluorescence in-situ hybridization of sex chromosomes in spermatozoa and spare preimplantation embryos of a Klinefelter 46,XY\/47,XXY male","volume":"15","author":"Bielanska","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1745-7262.2005.00023.x","article-title":"Birth after intracytoplasmic sperm injection of ejaculated spermatozoa from a man with mosaic Klinefelter\u2019s syndrome","volume":"7","author":"Akashi","year":"2005","journal-title":"Asian J. Androl."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/01485018208987032","article-title":"Paternity in Klinefelter\u2019s syndrome\u2014A case report","volume":"8","author":"Laron","year":"1982","journal-title":"Arch. Androl."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0015-0282(16)55334-5","article-title":"Fertility in a 47,XXY patient: Assessment of biological paternity by deoxyribonucleic acid fingerprinting","volume":"58","author":"Terzoli","year":"1992","journal-title":"Fertil. Steril."},{"key":"ref_112","first-page":"122","article-title":"Fertility in a patient diagnosed with klinefelter syndrome: A rare case report","volume":"7","author":"Alaidarous","year":"2019","journal-title":"Endocrinol. Metab. Int. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"989701","DOI":"10.3389\/fgene.2022.989701","article-title":"Birth of a boy after intracytoplasmic sperm injection using ejaculated spermatozoa from a nonmosaic klinefelter syndrome man with normal sperm motility: A case report","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/humupd\/dmg029","article-title":"PGD in 47,XXY Klinefelter\u2019s syndrome patients","volume":"9","author":"Staessen","year":"2003","journal-title":"Hum. Reprod. Update"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1093\/humrep\/16.12.2616","article-title":"Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter\u2019s syndrome","volume":"16","author":"Friedler","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/S0015-0282(97)00280-X","article-title":"Pregnancy after intracytoplasmic sperm injection with sperm from a man with a 47,XXY Klinefelter\u2019s karyotype","volume":"68","author":"Hinney","year":"1997","journal-title":"Fertil. Steril."},{"key":"ref_117","first-page":"88","article-title":"Ejaculated spermatozoa in patients with non-mosaic Klinefelter\u2019s syndrome","volume":"7","author":"Kitamura","year":"2000","journal-title":"Int. J. Urol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0015-0282(03)01157-9","article-title":"Partners of men with Klinefelter syndrome can benefit from assisted reproductive technologies","volume":"80","author":"Ulug","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/humrep\/12.11.2447","article-title":"Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47,XXY Klinefelter\u2019s syndrome","volume":"12","author":"Bourne","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0015-0282(00)00710-X","article-title":"Birth of healthy male twins after intracytoplasmic sperm injection of frozen-thawed testicular spermatozoa from a patient with nonmosaic Klinefelter syndrome","volume":"74","author":"Raziel","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1093\/humrep\/16.9.1909","article-title":"Birth of a healthy girl after ICSI with ejaculated spermatozoa from a man with non-mosaic Klinefelter\u2019s syndrome","volume":"16","author":"Toft","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/humrep\/deg070","article-title":"Reproductive genetic counselling in non-mosaic 47,XXY patients: Implications for preimplantation or prenatal diagnosis: Case report and review","volume":"18","author":"Tachdjian","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_123","first-page":"126","article-title":"Birth of healthy neonates after intracytoplasmic injection of ejaculated or testicular spermatozoa from men with nonmosaic Klinefelter\u2019s syndrome: A report of 2 cases","volume":"49","author":"Komori","year":"2004","journal-title":"J. Reprod. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"309","DOI":"10.31083\/j.ceog.2020.02.5201","article-title":"A patient with non-mosaic 47, XXY karyotype fathering a normal healthy infant using intracytoplasmic sperm injection (ICSI)\u2014A case report","volume":"47","author":"Ye","year":"2020","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1530\/EJE-07-0709","article-title":"Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes","volume":"158","author":"Aksglaede","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/andr.12597","article-title":"AMH and INSL3 in testicular and extragonadal pathophysiology: What do we know?","volume":"7","author":"Sansone","year":"2019","journal-title":"Andrology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1210\/jc.2002-021379","article-title":"Longitudinal studies of inhibin B levels in boys and young adults with Klinefelter syndrome","volume":"88","author":"Christiansen","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1210\/jc.2004-2257","article-title":"Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: Relationship to the luteinizing hormone-testosterone axis","volume":"90","author":"Bay","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/j.1651-2227.2011.02148.x","article-title":"Serum concentrations of Anti-M\u00fcllerian Hormone (AMH) in 95 patients with Klinefelter syndrome with or without cryptorchidism","volume":"100","author":"Aksglaede","year":"2011","journal-title":"Acta. Paediatr."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1111\/cen.14578","article-title":"Interpretation of reproductive hormones before, during and after the pubertal transition-Identifying health and disordered puberty","volume":"95","author":"Howard","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1093\/humrep\/deu124","article-title":"Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome","volume":"29","author":"Lottrup","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/ajmg.c.31787","article-title":"Germ cell loss in Klinefelter syndrome: When and why?","volume":"184","author":"Willems","year":"2020","journal-title":"Am. J. Med. Genet. C. Semin. Med. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"906381","DOI":"10.3389\/fendo.2022.906381","article-title":"AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications","volume":"13","author":"Edelsztein","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00441-015-2213-9","article-title":"INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio)","volume":"363","author":"Assis","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1365-2265.2007.02977.x","article-title":"Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome","volume":"67","author":"Bastida","year":"2007","journal-title":"Clin. Endocrinol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.fertnstert.2012.06.024","article-title":"The natural history of endocrine function and spermatogenesis in Klinefelter syndrome: What the data show","volume":"98","author":"Oates","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1095\/biolreprod.111.092593","article-title":"Diverse roles for sex hormone-binding globulin in reproduction","volume":"85","author":"Hammond","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1365-2265.1975.tb01547.x","article-title":"Hormonal studies in Klinefelter\u2019s syndrome","volume":"4","author":"Wang","year":"1975","journal-title":"Clin. Endocrinol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"324835","DOI":"10.1155\/2012\/324835","article-title":"Clinical Presentation of Klinefelter\u2019s Syndrome: Differences According to Age","volume":"2012","author":"Pacenza","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/j.1365-2605.2012.01269.x","article-title":"Reduced artery diameters in Klinefelter syndrome","volume":"35","author":"Foresta","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.2047-2927.2014.00190.x","article-title":"Intratesticular testosterone is increased in men with Klinefelter syndrome and may not be released into the bloodstream owing to altered testicular vascularization\u2013 a preliminary report","volume":"2","author":"Tuttelmann","year":"2014","journal-title":"Andrology"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Giudice, M.G., Vermeulen, M., and Wyns, C. (2019). Blood Testis Barrier and Somatic Cells Impairment in a Series of 35 Adult Klinefelter Syndrome Patients. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225717"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/humupd\/dmz038","article-title":"Age-related presence of spermatogonia in patients with Klinefelter syndrome: A systematic review and meta-analysis","volume":"26","author":"Deebel","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1093\/humrep\/dey025","article-title":"A diagnostic germ cell score for immature testicular tissue at risk of germ cell loss","volume":"33","author":"Heckmann","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/humrep\/dey094","article-title":"When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?","volume":"33","author":"Vloeberghs","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41419-018-0671-1","article-title":"Transcriptome analysis of the adult human Klinefelter testis and cellularity-matched controls reveals disturbed differentiation of Sertoli- and Leydig cells","volume":"9","author":"Winge","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3109\/15513818509078785","article-title":"Quantitative histology of human fetal testes in chromosomal disease","volume":"3","author":"Coerdt","year":"1985","journal-title":"Pediatr. Pathol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0140-6736(74)91608-0","article-title":"Letter: Klinefelter\u2019s syndrome in a fetus","volume":"2","author":"Murken","year":"1974","journal-title":"Lancet"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1210\/jc.2003-031624","article-title":"Inhibin B and anti-M\u00fcllerian hormone, but not testosterone levels, are normal in infants with nonmosaic Klinefelter syndrome","volume":"89","author":"Lahlou","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1210\/jc.2003-031725","article-title":"Klinefelter syndrome in adolescence: Onset of puberty is associated with accelerated germ cell depletion","volume":"89","author":"Raivio","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"45729","DOI":"10.1038\/srep45729","article-title":"Testis Transcriptome Modulation in Klinefelter Patients with Hypospermatogenesis","volume":"7","author":"Ferlin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0140-6736(92)92425-F","article-title":"Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte","volume":"340","author":"Palermo","year":"1992","journal-title":"Lancet"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/oxfordjournals.humrep.a138191","article-title":"Higher success rate by intracytoplasmic sperm injection than by subzonal insemination. Report of a second series of 300 consecutive treatment cycles","volume":"8","author":"Liu","year":"1993","journal-title":"Hum. Reprod."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/oxfordjournals.humrep.a138192","article-title":"High fertilization and implantation rates after intracytoplasmic sperm injection","volume":"8","author":"Nagy","year":"1993","journal-title":"Hum. Reprod."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/HUMREP\/10.6.1457","article-title":"Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia","volume":"10","author":"Devroey","year":"1995","journal-title":"Hum. Reprod."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/oxfordjournals.humrep.a019288","article-title":"Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia","volume":"11","author":"Devroey","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/oxfordjournals.humrep.a019004","article-title":"Correlation between testicular histology and outcome after intracytoplasmic sperm injection using testicular spermatozoa","volume":"11","author":"Tournaye","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/humrep\/12.1.80","article-title":"Are there any predictive factors for successful testicular sperm recovery in azoospermic patients?","volume":"12","author":"Tournaye","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/humrep\/14.suppl_1.71","article-title":"Surgical sperm recovery for intracytoplasmic sperm injection: Which method is to be preferred?","volume":"14","author":"Tournaye","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1093\/oxfordjournals.humrep.a019462","article-title":"Testicular sperm recovery in nine 47,XXY Klinefelter patients","volume":"11","author":"Tournaye","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_161","first-page":"69","article-title":"Surgical Sperm Retrieval for Intracytoplasmic Sperm Injection","volume":"20","author":"Tournaye","year":"1997","journal-title":"Int. J. Androl."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJM199802263380905","article-title":"Births after intracytoplasmic injection of sperm obtained by testicular extraction from men with nonmosaic Klinefelter\u2019s syndrome","volume":"338","author":"Palermo","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1210\/jc.2014-3083","article-title":"Preliminary results of a prospective study of testicular sperm extraction in young versus adult patients with nonmosaic 47,XXY Klinefelter syndrome","volume":"100","author":"Plotton","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/andr.12503","article-title":"A history of undescended testes in young men with Klinefelter syndrome does not reduce the chances for successful microsurgical testicular sperm extraction","volume":"6","author":"Ragab","year":"2018","journal-title":"Andrology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/humrep\/deh253","article-title":"Can biological or clinical parameters predict testicular sperm recovery in 47,XXY Klinefelter\u2019s syndrome patients?","volume":"19","author":"Vernaeve","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"6263","DOI":"10.1210\/jc.2004-2322","article-title":"Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome","volume":"90","author":"Schiff","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.urology.2006.05.028","article-title":"Aging may adversely affect testicular sperm recovery in patients with Klinefelter syndrome","volume":"68","author":"Bakircioglu","year":"2006","journal-title":"Urology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10815-006-9079-4","article-title":"Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm","volume":"24","author":"Kyono","year":"2007","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_169","first-page":"421","article-title":"Outcomes of Micro-Dissection TESE in Patients with Non-Mosaic Klinefelter\u2019s Syndrome without Hormonal Treatment","volume":"8","author":"Ozveri","year":"2015","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1439-0272.1995.tb02094.x","article-title":"Increased prolactin secretion and thyrotrophin response to thyrotrophin releasing hormone in Klinefelter\u2019s syndrome","volume":"27","author":"Kumanov","year":"1995","journal-title":"Andrologia"},{"key":"ref_171","first-page":"317","article-title":"Testicular function in Klinefelter syndrome","volume":"69","author":"Dunkel","year":"2008","journal-title":"Horm. Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1055\/s-0029-1202302","article-title":"Reproduction in men with Klinefelter syndrome: The past, the present, and the future","volume":"27","author":"Paduch","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/j.1651-2227.2011.02233.x","article-title":"Body composition, metabolic syndrome and type 2 diabetes in Klinefelter syndrome","volume":"100","author":"Gravholt","year":"2011","journal-title":"Acta. Paediatr."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.fertnstert.2012.05.026","article-title":"It\u2019s not all about the testes: Medical issues in Klinefelter patients","volume":"98","author":"Sokol","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.fertnstert.2005.05.053","article-title":"Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter\u2019s syndrome","volume":"84","author":"Okada","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.fertnstert.2011.01.005","article-title":"Klinefelter syndrome: Does it confer a bad prognosis in treatment of nonobstructive azoospermia?","volume":"95","author":"Bakircioglu","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.juro.2009.05.019","article-title":"Successful fertility treatment for Klinefelter\u2019s syndrome","volume":"182","author":"Ramasamy","year":"2009","journal-title":"J. Urol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1439-0272.2008.00875.x","article-title":"Age as only predictive factor for successful sperm recovery in patients with Klinefelter\u2019s syndrome","volume":"41","author":"Ferhi","year":"2009","journal-title":"Andrologia"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S1472-6483(10)60023-5","article-title":"TESE-ICSI in patients with non-mosaic Klinefelter syndrome: A comparative study","volume":"18","author":"Yarali","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.urology.2013.09.021","article-title":"Comparison of sperm retrieval and intracytoplasmic sperm injection outcome in patients with and without Klinefelter syndrome","volume":"83","author":"Sabbaghian","year":"2014","journal-title":"Urology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/andr.12067","article-title":"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\u2019s syndrome","volume":"3","author":"Rohayem","year":"2015","journal-title":"Andrology"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Ozer, C., Caglar Aytac, P., Goren, M.R., Toksoz, S., Gul, U., and Turunc, T. (2018). Sperm retrieval by microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in nonobstructive azoospermic patients with Klinefelter syndrome. Andrologia, 50.","DOI":"10.1111\/and.12983"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"636629","DOI":"10.3389\/frph.2021.636629","article-title":"How Successful Is Surgical Sperm Retrieval in Klinefelter Syndrome?","volume":"3","author":"Kailash","year":"2021","journal-title":"Front. Reprod. Health"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0015-0282(02)03092-3","article-title":"Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy","volume":"77","author":"Madgar","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.fertnstert.2020.05.043","article-title":"Role of treatment with human chorionic gonadotropin and clinical parameters on testicular sperm recovery with microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in 184 Klinefelter syndrome patients","volume":"114","author":"Guo","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/and.12428","article-title":"Outcome of testicular sperm extraction in nonmosaic Klinefelter syndrome patients: What is the best approach?","volume":"48","author":"Majzoub","year":"2016","journal-title":"Andrologia"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/jog.13090","article-title":"Outcome of intracytoplasmic sperm injection using fresh and cryopreserved-thawed test\u0131cular spermatozoa in 83 azoospermic men with Klinefelter syndrome","volume":"42","author":"Vicdan","year":"2016","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/humupd\/dmx008","article-title":"Sperm recovery and ICSI outcomes in Klinefelter syndrome: A systematic review and meta-analysis","volume":"23","author":"Corona","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.urology.2004.07.013","article-title":"Successful testicular sperm extraction in Korean Klinefelter syndrome","volume":"64","author":"Seo","year":"2004","journal-title":"Urology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.fertnstert.2008.07.1703","article-title":"High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction","volume":"92","author":"Ramasamy","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.2047-2927.2013.00157.x","article-title":"Should repeated TESE be performed following a failed TESE in men with Klinefelter Syndrome?","volume":"2","author":"Haliloglu","year":"2014","journal-title":"Andrology"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.urology.2007.03.056","article-title":"Clinical comparison of successful and failed microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome","volume":"70","author":"Koga","year":"2007","journal-title":"Urology"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/humrep\/det046","article-title":"Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome","volume":"28","author":"Greco","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/S0015-0282(03)00403-5","article-title":"Low levels of serum inhibin B do not exclude successful sperm recovery in men with nonmosaic Klinefelter syndrome","volume":"79","author":"Westlander","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1365-2605.2008.00921.x","article-title":"Low semen volume in 47 adolescents and adults with 47,XXY Klinefelter or 46,XX male syndrome","volume":"32","author":"Aksglaede","year":"2009","journal-title":"Int. J. Androl."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1023\/A:1014792922874","article-title":"Birth of a healthy male after frozen thawed blastocyst transfer following intracytoplasmic injection of frozen thawed testicular spermatozoa from a man with nonmosaic Klinefelter\u2019s syndrome","volume":"19","author":"Rosenlund","year":"2002","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000093426","article-title":"An ongoing pregnancy after frozen thawed embryo transfer in a patient with Klinefelter\u2019s syndrome","volume":"62","author":"Yarali","year":"2006","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.fertnstert.2011.06.011","article-title":"Birth of a healthy boy using fresh testicular sperm in a patient with Klinefelter syndrome combined with Kartagener syndrome","volume":"96","author":"Vicdan","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1093\/humrep\/13.7.1887","article-title":"A birth in non-mosaic Klinefelter\u2019s syndrome after testicular fine needle aspiration, intracytoplasmic sperm injection and preimplantation genetic diagnosis","volume":"13","author":"Reubinoff","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_200","first-page":"424","article-title":"Births using frozen-thawed testicular spermatozoa and frozen-thawed embryos in two azoospermic patients with non-mosaic Klinefelter\u2019s Syndrome","volume":"8","author":"Vicdan","year":"2007","journal-title":"J. Turk. Ger. Gynecol. Assoc."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0015-0282(99)00151-X","article-title":"Birth of twin males with normal karyotype after intracytoplasmic sperm injection with use of testicular spermatozoa from a nonmosaic patient with Klinefelter\u2019s syndrome","volume":"71","author":"Nodar","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/humrep\/14.2.368","article-title":"Birth of a healthy neonate following the intracytoplasmic injection of testicular spermatozoa from a patient with Klinefelter\u2019s syndrome","volume":"14","author":"Friedler","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0015-0282(01)02734-0","article-title":"Klinefelter\u2019s syndrome and assisted reproduction","volume":"76","author":"Greco","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/S0015-0282(01)02830-8","article-title":"Birth of two infants with normal karyotype after intracytoplasmic injection of sperm obtained by testicular extraction from two men with nonmosaic Klinefelter\u2019s syndrome","volume":"76","author":"Poulakis","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1093\/humrep\/16.11.2347","article-title":"Pregnancy achieved following ICSI from a man with Klinefelter\u2019s syndrome and spinal cord injury","volume":"16","author":"Kyono","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fertnstert.2012.06.001","article-title":"Klinefelter syndrome: An argument for early aggressive hormonal and fertility management","volume":"98","author":"Mehta","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/humrep\/14.1.131","article-title":"Testicular sperm extraction: Microdissection improves sperm yield with minimal tissue excision","volume":"14","author":"Schlegel","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.fertnstert.2005.05.033","article-title":"Four pregnancies in nonmosaic Klinefelter\u2019s syndrome using cryopreserved-thawed testicular spermatozoa","volume":"84","author":"Okada","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"366","DOI":"10.21037\/tau.2019.04.08","article-title":"Comparison and outcomes of nonobstructive azoospermia patients with different etiology undergoing MicroTESE and ICSI treatments","volume":"8","author":"Chen","year":"2019","journal-title":"Transl. Androl. Urol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/aja.2012.141","article-title":"Microdissection testicular sperm extraction: An update","volume":"15","author":"Dabaja","year":"2013","journal-title":"Asian J. Androl."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1093\/oxfordjournals.humrep.a019463","article-title":"Preimplantation diagnosis for X and Y normality in embryos from three Klinefelter patients","volume":"11","author":"Staessen","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/humrep\/15.8.1804","article-title":"A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter\u2019s syndrome: Case report","volume":"15","author":"Strassburger","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1046\/j.1439-0272.2002.00498.x","article-title":"Use of a highly sensitive quantitative telomerase assay in intracytoplasmic sperm injection programmes for the treatment of 47,XXY non-mosaic Klinefelter men","volume":"34","author":"Yamamoto","year":"2002","journal-title":"Andrologia"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1028-4559(09)60062-0","article-title":"Outcome of Intracytoplasmic Injection of Sperm Obtained by Testicular Sperm Extraction from 14 Azoospermic Men Suffering from 47,XXY Non-mosaic Klinefelter\u2019s Syndrome","volume":"43","author":"Chiang","year":"2004","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"991.e5","DOI":"10.1016\/j.fertnstert.2007.04.039","article-title":"Birth of a healthy boy after fertilization of cryopreserved oocytes with cryopreserved testicular spermatozoa from a man with nonmosaic Klinefelter syndrome","volume":"89","author":"Greco","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.urology.2008.02.022","article-title":"Androgen decline in patients with nonobstructive azoospemia after microdissection testicular sperm extraction","volume":"72","author":"Takada","year":"2008","journal-title":"Urology"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.fertnstert.2013.06.010","article-title":"Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor","volume":"100","author":"Mehta","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1093\/humrep\/det084","article-title":"The feasibility of fertility preservation in adolescents with Klinefelter syndrome","volume":"28","author":"Rives","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jpeds.2015.12.028","article-title":"Sperm Retrieval in Adolescents and Young Adults with Klinefelter Syndrome: A Prospective, Pilot Study","volume":"170","author":"Nahata","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/rmb2.12092","article-title":"Microdissection testicular sperm extraction in five Japanese patients with non-mosaic Klinefelter\u2019s syndrome","volume":"17","author":"Chihara","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s10815-020-01818-2","article-title":"ART strategies in Klinefelter syndrome","volume":"37","author":"Chen","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.fertnstert.2013.10.012","article-title":"Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: A meta-analysis","volume":"101","author":"Ohlander","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1093\/humrep\/12.3.468","article-title":"Incidence of diploid and disomic sperm nuclei in 45 infertile men","volume":"12","author":"Guttenbach","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s004390050391","article-title":"Segregation of sex chromosomes into sperm nuclei in a man with 47,XXY Klinefelter\u2019s karyotype: A FISH analysis","volume":"99","author":"Guttenbach","year":"1997","journal-title":"Hum. Genet."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/14.4.946","article-title":"Klinefelter\u2019s syndrome in the male infertility clinic","volume":"14","author":"Okada","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/S0140-6736(00)05201-6","article-title":"Risk of trisomy 21 in offspring of patients with Klinefelter\u2019s syndrome","volume":"357","author":"Hennebicq","year":"2001","journal-title":"Lancet"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/S0015-0282(03)00343-1","article-title":"An increased incidence of autosomal aneuploidies in spermatozoa from a patient with Klinefelter\u2019s syndrome","volume":"79","author":"Morel","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1159\/000086905","article-title":"Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities","volume":"111","author":"Ferlin","year":"2005","journal-title":"Cytogenet. Genome Res."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/rmb2.12029","article-title":"Genetic risk of Klinefelter\u2019s syndrome in assisted reproductive technology","volume":"16","author":"Miki","year":"2017","journal-title":"Reprod. Med. Biol."},{"key":"ref_230","unstructured":"Turnpenny, P.D., and Ellard, S. (2012). Emery\u2019s Elements of Medical Genetics, Elsevier Churchill Livingstone. [14th ed.]."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ejhg.2008.265","article-title":"Incidence of non-age-dependent chromosomal abnormalities: A population-based study on 88965 amniocenteses","volume":"17","author":"Forabosco","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/(SICI)1097-0223(199704)17:4<363::AID-PD79>3.0.CO;2-O","article-title":"47,XXY (Klinefelter syndrome) and 47,XYY: Estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling","volume":"17","author":"Abramsky","year":"1997","journal-title":"Prenat. Diagn."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1210\/jc.2005-1077","article-title":"Mortality in patients with Klinefelter syndrome in Britain: A cohort study","volume":"90","author":"Swerdlow","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5694\/j.1326-5377.2011.tb04141.x","article-title":"The prevalence and diagnosis rates of Klinefelter syndrome: An Australian comparison","volume":"194","author":"Herlihy","year":"2011","journal-title":"Med. J. Aust."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Pook, C.J., Cocca, A., Grandone, A., Al-Hussini, M., and Lam, W. (2021). The Evidence for Fertility Preservation in Pediatric Klinefelter Syndrome. Front. Reprod. Health., 3.","DOI":"10.3389\/frph.2021.629179"},{"key":"ref_236","first-page":"56","article-title":"Infertility in Patients With Klinefelter Syndrome: Optimal Timing for Sperm and Testicular Tissue Cryopreservation","volume":"20","author":"Hawksworth","year":"2018","journal-title":"Rev. Urol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1093\/humrep\/dew179","article-title":"Klinefelter syndrome and fertility: Sperm preservation should not be offered to children with Klinefelter syndrome","volume":"31","author":"Franik","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"102177","DOI":"10.1016\/j.jogoh.2021.102177","article-title":"Fertility preservation in young men with Klinefelter syndrome: A systematic review","volume":"50","author":"Ly","year":"2021","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1111\/andr.12249","article-title":"Testicular function during puberty and young adulthood in patients with Klinefelter\u2019s syndrome with and without spermatozoa in seminal fluid","volume":"4","author":"Rohayem","year":"2016","journal-title":"Andrology"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/647\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:47:44Z","timestamp":1760122064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,4]]},"references-count":239,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["genes14030647"],"URL":"https:\/\/doi.org\/10.3390\/genes14030647","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,4]]}}}