{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:42:27Z","timestamp":1791301347609,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod Biol Endocrinol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The production of spermatozoa, a process known as spermatogenesis, is primarily controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-driven testosterone. LH acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing LH activity can effectively restore spermatogenesis in males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of male infertility is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of LH activity in spermatogenesis regulation and explore available preparations for therapeutic use. We also examine the evidence regarding the effectiveness of LH-containing drugs in treating specific male infertility conditions and identify the main areas for future research. Our review highlights the critical role of LH in spermatogenesis and emphasizes the potential of LH-containing drugs in treating male infertility. However, further research is required to completely elucidate the mechanisms underlying the effects of LH activity on sperm production and to establish the most effective dosages and treatment durations.\n<\/jats:p>","DOI":"10.1186\/s12958-024-01333-4","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:34:30Z","timestamp":1736739270000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The role of luteinizing hormone activity in spermatogenesis: from physiology to clinical practice"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-9680","authenticated-orcid":false,"given":"Sandro C.","family":"Esteves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-5366","authenticated-orcid":false,"given":"Peter","family":"Humaidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"1333_CR1","doi-asserted-by":"publisher","first-page":"102310","DOI":"10.1016\/j.bpobgyn.2022.102310","volume":"86","author":"SC Esteves","year":"2023","unstructured":"Esteves SC, Achermann APP, Simoni M, Santi D, Casarini L. Male infertility and gonadotropin treatment: what can we learn from real-world data? Best Pract Res Clin Obstet Gynaecol. 2023;86:102310.","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"issue":"Suppl 1","key":"1333_CR2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.6061\/clinics\/2013(Sup01)09","volume":"68","author":"R Fraietta","year":"2013","unstructured":"Fraietta R, Zylberstejn DS, Esteves SC. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo). 2013;68(Suppl 1):81\u20138.","journal-title":"Clinics (Sao Paulo)"},{"key":"1333_CR3","doi-asserted-by":"publisher","first-page":"763","DOI":"10.3389\/fendo.2018.00763","volume":"9","author":"OO Oduwole","year":"2018","unstructured":"Oduwole OO, Peltoketo H, Huhtaniemi IT. Role of follicle-stimulating hormone in spermatogenesis. Front Endocrinol (Lausanne). 2018;9:763.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1333_CR4","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s11255-011-0065-0","volume":"44","author":"L Yang","year":"2012","unstructured":"Yang L, Zhang SX, Dong Q, Xiong ZB, Li X. Application of hormonal treatment in hypogonadotropic hypogonadism: more than ten years experience. Int Urol Nephrol. 2012;44:393\u20139.","journal-title":"Int Urol Nephrol"},{"key":"1333_CR5","doi-asserted-by":"publisher","first-page":"279","DOI":"10.6061\/clinics\/2014(04)10","volume":"69","author":"B Le\u00e3o Rde","year":"2014","unstructured":"Le\u00e3o Rde B, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics (Sao Paulo). 2014;69:279\u201393.","journal-title":"Clinics (Sao Paulo)"},{"key":"1333_CR6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1507\/endocrj.EJ17-0001","volume":"64","author":"K Shiraishi","year":"2017","unstructured":"Shiraishi K, Matsuyama H. Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [review]. Endocr J. 2017;64:123\u201331.","journal-title":"Endocr J"},{"key":"1333_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1210\/jcem-48-2-279","volume":"48","author":"L Axelrod","year":"1979","unstructured":"Axelrod L, Neer RM, Kliman B. Hypogonadism in a male with immunologically active, biologically inactive luteinizing hormone: an exception to a venerable rule. J Clin Endocrinol Metab. 1979;48:279\u201387.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR8","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1056\/NEJMoa071999","volume":"357","author":"A Lofrano-Porto","year":"2007","unstructured":"Lofrano-Porto A, Barra GB, Giacomini LA, Nascimento PP, Latronico AC, Casulari LA, et al. Luteinizing hormone beta mutation and hypogonadism in men and women. N Engl J Med. 2007;357:897\u2013904.","journal-title":"N Engl J Med"},{"key":"1333_CR9","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1056\/NEJMoa040326","volume":"351","author":"H Valdes-Socin","year":"2004","unstructured":"Valdes-Socin H, Salvi R, Daly AF, Gaillard RC, Quatresooz P, Tebeu PM, et al. Hypogonadism in a patient with a mutation in the luteinizing hormone beta-subunit gene. N Engl J Med. 2004;351:2619\u201325.","journal-title":"N Engl J Med"},{"key":"1333_CR10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1056\/NEJM199201163260306","volume":"326","author":"J Weiss","year":"1992","unstructured":"Weiss J, Axelrod L, Whitcomb RW, Harris PE, Crowley WF, Jameson JL. Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing hormone. N Engl J Med. 1992;326:179\u201383.","journal-title":"N Engl J Med"},{"key":"1333_CR11","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1210\/jcem.85.6.6636","volume":"85","author":"J Gromoll","year":"2000","unstructured":"Gromoll J, Eiholzer U, Nieschlag E, Simoni M. Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab. 2000;85:2281\u20136.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR12","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1210\/jc.2002-021946","volume":"88","author":"T M\u00fcller","year":"2003","unstructured":"M\u00fcller T, Gromoll J, Simoni M. Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action. J Clin Endocrinol Metab. 2003;88:2242\u20139.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR13","doi-asserted-by":"publisher","first-page":"12735","DOI":"10.3390\/ijms222312735","volume":"22","author":"OO Oduwole","year":"2021","unstructured":"Oduwole OO, Huhtaniemi IT, Misrahi M. The roles of luteinizing hormone, follicle-stimulating hormone and testosterone in spermatogenesis and folliculogenesis revisited. Int J Mol Sci. 2021;22:12735.","journal-title":"Int J Mol Sci"},{"key":"1333_CR14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/jc.2008-1584","volume":"94","author":"H Valdes-Socin","year":"2009","unstructured":"Valdes-Socin H, Salvi R, Thiry A, Daly AF, Pralong FP, Gaillard R, et al. Testicular effects of isolated luteinizing hormone deficiency and reversal by long-term human chorionic gonadotropin treatment. J Clin Endocrinol Metab. 2009;94:3\u20134.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR15","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.1210\/jc.2004-2465","volume":"90","author":"MM Grumbach","year":"2005","unstructured":"Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005;90:3122\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR16","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1590\/s1677-5538.ibju.2022.99.13","volume":"48","author":"RJ Laursen","year":"2022","unstructured":"Laursen RJ, Alsbjerg B, Elbaek HO, Povlsen BB, Jensen KBS, Lykkegaard J, et al. Recombinant gonadotropin therapy to improve spermatogenesis in nonobstructive azoospermic patients: a proof of concept study. Int Braz J Urol. 2022;48:471\u201381.","journal-title":"Int Braz J Urol"},{"key":"1333_CR17","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.3390\/jcm10143144","volume":"10","author":"DL Andrade","year":"2021","unstructured":"Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med. 2021;10:3144.","journal-title":"J Clin Med"},{"key":"1333_CR18","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1530\/EJE-07-0876","volume":"159","author":"A Cailleux-Bounacer","year":"2008","unstructured":"Cailleux-Bounacer A, Reznik Y, Cauliez B, Menard JF, Duparc C, Kuhn JM. Evaluation of endocrine testing of Leydig cell function using extractive and recombinant human chorionic gonadotropin and different doses of recombinant human LH in normal men. Eur J Endocrinol. 2008;159:171\u20138.","journal-title":"Eur J Endocrinol"},{"key":"1333_CR19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1080\/13685538.2016.1276161","volume":"20","author":"D Santi","year":"2017","unstructured":"Santi D, Spaggiari G, Casarini L, Fanelli F, Mezzullo M, Pagotto U, et al. Central hypogonadism due to a giant, \u201csilent\u201d FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Aging Male. 2017;20:96\u2013101.","journal-title":"Aging Male"},{"key":"1333_CR20","doi-asserted-by":"publisher","first-page":"R994","DOI":"10.1152\/ajpregu.00314.2012","volume":"303","author":"JD Veldhuis","year":"2012","unstructured":"Veldhuis JD, Liu PY, Takahashi PY, Weist SM, Wigham JR. Analysis of the impact of intravenous LH pulses versus continuous LH infusion on testosterone secretion during GnRH-receptor blockade. Am J Physiol Regul Integr Comp Physiol. 2012;303:R994\u20131002.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1333_CR21","doi-asserted-by":"publisher","first-page":"459","DOI":"10.4103\/1008-682X.148719","volume":"17","author":"SC Esteves","year":"2015","unstructured":"Esteves SC. Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl. 2015;17:459\u201370.","journal-title":"Asian J Androl"},{"key":"1333_CR22","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1210\/endo-124-6-3043","volume":"124","author":"BR Zirkin","year":"1989","unstructured":"Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989;124:3043\u20139.","journal-title":"Endocrinology"},{"key":"1333_CR23","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1111\/j.2047-2927.2013.00141.x","volume":"1","author":"E Shinjo","year":"2013","unstructured":"Shinjo E, Shiraishi K, Matsuyama H. The effect of human chorionic gonadotropin-based hormonal therapy on intratesticular testosterone levels and spermatogonial DNA synthesis in men with non-obstructive azoospermia. Andrology. 2013;1:929\u201335.","journal-title":"Andrology"},{"key":"1333_CR24","doi-asserted-by":"publisher","first-page":"R7","DOI":"10.1016\/0303-7207(91)90130-K","volume":"78","author":"AP Themmen","year":"1991","unstructured":"Themmen AP, Blok LJ, Post M, Baarends WM, Hoogerbrugge JW, Parmentier M, et al. Follitropin receptor down-regulation involves a cAMP-dependent post-transcriptional decrease of receptor mRNA expression. Mol Cell Endocrinol. 1991;78:R7\u201313.","journal-title":"Mol Cell Endocrinol"},{"key":"1333_CR25","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1093\/humrep\/deh255","volume":"19","author":"C Foresta","year":"2004","unstructured":"Foresta C, Bettella A, Spolaore D, Merico M, Rossato M, Ferlin A. Suppression of the high endogenous levels of plasma FSH in infertile men are associated with improved Sertoli cell function as reflected by elevated levels of plasma inhibin B. Hum Reprod. 2004;19:1431\u20137.","journal-title":"Hum Reprod"},{"key":"1333_CR26","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/andr.12809","volume":"9","author":"SC Esteves","year":"2021","unstructured":"Esteves SC, Lombardo F, Garrido N, Alvarez J, Zini A, Colpi GM, et al. SARS-CoV-2 pandemic and repercussions for male infertility patients: a proposal for the individualized provision of andrological services. Andrology. 2021;9:10\u20138.","journal-title":"Andrology"},{"key":"1333_CR27","doi-asserted-by":"publisher","first-page":"e14251","DOI":"10.1111\/and.14251","volume":"54","author":"SW Andrabi","year":"2022","unstructured":"Andrabi SW, Saini P, Joshi M, Mehta P, Makker GC, Mishra G, et al. HCG therapy in azoospermic men with lower or borderline testosterone levels and the prognostic value of Y-deletion analysis in its outcome. Andrologia. 2022;54:e14251.","journal-title":"Andrologia"},{"key":"1333_CR28","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1111\/j.1365-2605.1982.tb00278.x","volume":"5","author":"WB Schill","year":"1982","unstructured":"Schill WB, J\u00fcngst D, Unterburger P, Braun S. Combined hMG\/hCG treatment in subfertile men with idiopathic normogonadotrophic oligozoospermia. Int J Androl. 1982;5:467\u201377.","journal-title":"Int J Androl"},{"key":"1333_CR29","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1210\/jcem-65-6-1081","volume":"65","author":"UA Knuth","year":"1987","unstructured":"Knuth UA, H\u00f6nigl W, Bals-Pratsch M, Schleicher G, Nieschlag E. Treatment of severe oligospermia with human chorionic gonadotropin\/human menopausal gonadotropin: a placebo-controlled, double blind trial. J Clin Endocrinol Metab. 1987;65:1081\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR30","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/S0015-0282(98)00008-9","volume":"69","author":"C Foresta","year":"1998","unstructured":"Foresta C, Bettella A, Ferlin A, Garolla A, Rossato M. Evidence for a stimulatory role of follicle-stimulating hormone on the spermatogonial population in adult males. Fertil Steril. 1998;69:636\u201342.","journal-title":"Fertil Steril"},{"key":"1333_CR31","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1080\/13685538.2019.1590696","volume":"23","author":"S La Vignera","year":"2020","unstructured":"La Vignera S, Condorelli RA, Duca Y, Mongioi LM, Cannarella R, Giacone F, et al. FSH therapy for idiopathic male infertility: four schemes are better than one. Aging Male. 2020;23:750\u20135.","journal-title":"Aging Male"},{"key":"1333_CR32","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1007\/s11255-021-02979-4","volume":"53","author":"APP Achermann","year":"2021","unstructured":"Achermann APP, Pereira TA, Esteves SC. Microdissection testicular sperm extraction (micro-TESE) in men with infertility due to nonobstructive azoospermia: summary of current literature. Int Urol Nephrol. 2021;53:2193\u2013210.","journal-title":"Int Urol Nephrol"},{"key":"1333_CR33","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1111\/andr.13405","volume":"11","author":"SC Esteves","year":"2023","unstructured":"Esteves SC, Coimbra I, Hallak J. Surgically retrieved spermatozoa for ICSI cycles in non-azoospermic males with high sperm DNA fragmentation in semen. Andrology. 2023;11:1613\u201334.","journal-title":"Andrology"},{"key":"1333_CR34","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41585-018-0051-8","volume":"15","author":"SC Esteves","year":"2018","unstructured":"Esteves SC, Roque M, Bedoschi G, Haahr T, Humaidan P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol. 2018;15:535\u201362.","journal-title":"Nat Rev Urol"},{"key":"1333_CR35","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1093\/humupd\/dmac016","volume":"28","author":"T Tharakan","year":"2022","unstructured":"Tharakan T, Corona G, Foran D, Salonia A, Sofikitis N, Giwercman A, et al. Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis. Hum Reprod Update. 2022;28:609\u201328.","journal-title":"Hum Reprod Update"},{"key":"1333_CR36","doi-asserted-by":"publisher","first-page":"6263","DOI":"10.1210\/jc.2004-2322","volume":"90","author":"JD Schiff","year":"2005","unstructured":"Schiff JD, Palermo GD, Veeck LL, Goldstein M, Rosenwaks Z, Schlegel PN. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90:6263\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"1333_CR37","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.fertnstert.2005.12.055","volume":"86","author":"H Selman","year":"2006","unstructured":"Selman H, De Santo M, Sterzik K, Cipollone G, Aragona C, El-Danasouri I. Rescue of spermatogenesis arrest in azoospermic men after long-term gonadotropin treatment. Fertil Steril. 2006;86:466\u20138.","journal-title":"Fertil Steril"},{"key":"1333_CR38","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1093\/humrep\/der404","volume":"27","author":"K Shiraishi","year":"2012","unstructured":"Shiraishi K, Ohmi C, Shimabukuro T, Matsuyama H. Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Hum Reprod. 2012;27:331\u20139.","journal-title":"Hum Reprod"},{"key":"1333_CR39","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.juro.2012.04.002","volume":"188","author":"JE Reifsnyder","year":"2012","unstructured":"Reifsnyder JE, Ramasamy R, Husseini J, Schlegel PN. Role of optimizing testosterone before microdissection testicular sperm extraction in men with nonobstructive azoospermia. J Urol. 2012;188:532\u20136.","journal-title":"J Urol"},{"key":"1333_CR40","doi-asserted-by":"publisher","first-page":"E110","DOI":"10.1111\/j.1464-410X.2012.11485.x","volume":"111","author":"A Hussein","year":"2013","unstructured":"Hussein A, Ozgok Y, Ross L, Rao P, Niederberger C. Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study. BJU Int. 2013;111:E110\u20134.","journal-title":"BJU Int"},{"key":"1333_CR41","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/iju.13076","volume":"23","author":"K Shiraishi","year":"2016","unstructured":"Shiraishi K, Ishikawa T, Watanabe N, Iwamoto T, Matsuyama H. Salvage hormonal therapy after failed microdissection testicular sperm extraction: a multi-institutional prospective study. Int J Urol. 2016;23:496\u2013500.","journal-title":"Int J Urol"},{"key":"1333_CR42","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s12958-018-0401-7","volume":"16","author":"X Hu","year":"2018","unstructured":"Hu X, Ding Z, Hong Z, Zou Z, Feng Y, Zhu R, et al. Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study. Reprod Biol Endocrinol. 2018;16:91.","journal-title":"Reprod Biol Endocrinol"},{"key":"1333_CR43","doi-asserted-by":"publisher","first-page":"e13176","DOI":"10.1111\/and.13176","volume":"51","author":"MK Amer","year":"2019","unstructured":"Amer MK, Ahmed AR, Abdel Hamid AA, GamalEl Din SF. Can spermatozoa be retrieved in non-obstructive azoospermic patients with high FSH level? A retrospective cohort study. Andrologia. 2019;51:e13176.","journal-title":"Andrologia"},{"key":"1333_CR44","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1177\/0391560320913401","volume":"87","author":"MK Amer","year":"2020","unstructured":"Amer MK, Ahmed HEH, GamalEl Din SF, Fawzy Megawer A, Ahmed AR. Evaluation of neoadjuvant gonadotropin administration with downregulation by testosterone prior to second time microsurgical testicular sperm extraction: a prospective case-control study. Urologia. 2020;87:185\u201390.","journal-title":"Urologia"},{"key":"1333_CR45","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.fertnstert.2020.05.043","volume":"114","author":"F Guo","year":"2020","unstructured":"Guo F, Fang A, Fan Y, Fu X, Lan Y, Liu M, et al. 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. Fertil Steril. 2020;114:997\u20131005.","journal-title":"Fertil Steril"},{"key":"1333_CR46","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12958-022-00934-1","volume":"20","author":"T Peng","year":"2022","unstructured":"Peng T, Liao C, Ye X, Chen Z, Lan Y, Fu X, et al. Gonadotropins treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia: a single-center cohort study. Reprod Biol Endocrinol. 2022;20:61.","journal-title":"Reprod Biol Endocrinol"},{"key":"1333_CR47","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s11255-019-02091-8","volume":"51","author":"RJ Laursen","year":"2019","unstructured":"Laursen RJ, Elbaek HO, Povlsen BB, Lykkegaard J, Jensen KBS, Esteves SC, et al. Hormonal stimulation of spermatogenesis: a new way to treat the infertile male with non-obstructive azoospermia? Int Urol Nephrol. 2019;51:453\u20136.","journal-title":"Int Urol Nephrol"},{"key":"1333_CR48","doi-asserted-by":"publisher","unstructured":"Esteves SC, Achermann APP, Miyaoka R, Verza S Jr, Fregonesi A, Riccetto CLZ. Clinical factors impacting microdissection testicular sperm extraction success in hypogonadal men with nonobstructive azoospermia. Fertil Steril. 2024;122(4):636\u201347. https:\/\/doi.org\/10.1016\/j.fertnstert.2024.06.013.","DOI":"10.1016\/j.fertnstert.2024.06.013"},{"key":"1333_CR49","doi-asserted-by":"publisher","first-page":"e13874","DOI":"10.1111\/and.13874","volume":"53","author":"SC Esteves","year":"2021","unstructured":"Esteves SC, Zini A, Coward RM, Evenson DP, Gos\u00e1lvez J, Lewis SEM, Sharma R, Humaidan P. Sperm DNA fragmentation testing: summary evidence and clinical practice recommendations. Andrologia. 2021;53:e13874.","journal-title":"Andrologia"},{"key":"1333_CR50","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1055\/s-0043-1777324","volume":"41","author":"JLM Nielsen","year":"2023","unstructured":"Nielsen JLM, Majzoub A, Esteves S, Humaidan P. Unraveling the impact of sperm DNA fragmentation on reproductive outcomes. Semin Reprod Med. 2023;41:241\u201357.","journal-title":"Semin Reprod Med"},{"key":"1333_CR51","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/andr.12724","volume":"8","author":"SC Esteves","year":"2020","unstructured":"Esteves SC, Santi D, Simoni M. An update on clinical and surgical interventions to reduce sperm DNA fragmentation in infertile men. Andrology. 2020;8:53\u201381.","journal-title":"Andrology"},{"key":"1333_CR52","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2119\/molmed.2014.00158","volume":"21","author":"M Muratori","year":"2015","unstructured":"Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, et al. Investigation on the origin of sperm DNA Fragmentation: role of apoptosis, immaturity and oxidative stress. Mol Med. 2015;21:109\u201322.","journal-title":"Mol Med"},{"key":"1333_CR53","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3389\/fendo.2018.00383","volume":"9","author":"N Colacurci","year":"2018","unstructured":"Colacurci N, De Leo V, Ruvolo G, Piomboni P, Caprio F, Pivonello R, et al. Recombinant FSH improves sperm DNA damage in male infertility: a phase II Clinical Trial. Front Endocrinol (Lausanne). 2018;9:383.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1333_CR54","doi-asserted-by":"publisher","first-page":"588","DOI":"10.2164\/jandrol.111.013326","volume":"3","author":"N Colacurci","year":"2012","unstructured":"Colacurci N, Monti MG, Fornaro F, Izzo G, Izzo P, Trotta C, et al. Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia. J Androl. 2012;3:588\u201393.","journal-title":"J Androl"},{"key":"1333_CR55","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1093\/humrep\/13.3.596","volume":"13","author":"A Kamischke","year":"1998","unstructured":"Kamischke A, Behre HM, Bergmann M, Simoni M, Sch\u00e4fer T, Nieschlag E. Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial. Hum Reprod. 1998;13:596\u2013603.","journal-title":"Hum Reprod"},{"key":"1333_CR56","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.mce.2014.06.013","volume":"393","author":"L Casarini","year":"2014","unstructured":"Casarini L, Moriondo V, Marino M, Adversi F, Capodanno F, Grisolia C, et al. FSHR polymorphism p.N680S mediates different responses to FSH in vitro. Mol Cell Endocrinol. 2014;393:83\u201391.","journal-title":"Mol Cell Endocrinol"},{"key":"1333_CR57","doi-asserted-by":"publisher","first-page":"103647","DOI":"10.1016\/j.rbmo.2023.103647","volume":"48","author":"SC Esteves","year":"2023","unstructured":"Esteves SC, Humaidan P, Ubaldi FM, Alviggi C, Antonio L, Barratt CLR, et al. APHRODITE criteria: addressing male patients with hypogonadism and\/or infertility owing to altered idiopathic testicular function. Reprod BioMed Online. 2023;48:103647.","journal-title":"Reprod BioMed Online"},{"key":"1333_CR58","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/andr.12886","volume":"9","author":"L Farahani","year":"2021","unstructured":"Farahani L, Tharakan T, Yap T, Ramsay JW, Jayasena CN, Minhas S. The semen microbiome and its impact on sperm function and male fertility: a systematic review and meta-analysis. Andrology. 2021;9:115\u201344.","journal-title":"Andrology"},{"key":"1333_CR59","doi-asserted-by":"publisher","first-page":"1348186","DOI":"10.3389\/fendo.2024.1348186","volume":"15","author":"FTL Neto","year":"2024","unstructured":"Neto FTL, Viana MC, Cariati F, Conforti A, Alviggi C, Esteves SC. Effect of environmental factors on seminal microbiome and impact on sperm quality. Front Endocrinol (Lausanne). 2024;15:1348186.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"5","key":"1333_CR60","doi-asserted-by":"publisher","first-page":"654","DOI":"10.3390\/genes12050654","volume":"12","author":"C Pagliuca","year":"2021","unstructured":"Pagliuca C, Cariati F, Bagnulo F, Scaglione E, Carotenuto C, Farina F, et al. Microbiological evaluation and sperm DNA fragmentation in semen samples of patients undergoing fertility investigation. Genes (Basel). 2021;12(5):654.","journal-title":"Genes (Basel)"}],"container-title":["Reproductive Biology and Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12958-024-01333-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12958-024-01333-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12958-024-01333-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T08:05:46Z","timestamp":1747209946000},"score":1,"resource":{"primary":{"URL":"https:\/\/rbej.biomedcentral.com\/articles\/10.1186\/s12958-024-01333-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":60,"journal-issue":{"issue":"S1","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["1333"],"URL":"https:\/\/doi.org\/10.1186\/s12958-024-01333-4","relation":{},"ISSN":["1477-7827"],"issn-type":[{"value":"1477-7827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,13]]},"assertion":[{"value":"28 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SCE and PH declare receipt of unrestricted research grants from Merck; and lecture fees from Merck, MedEA, and Event Planet.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}