{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:02:36Z","timestamp":1792141356975,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hypogonadotropic hypogonadism (HH) is a treatable cause of nonobstructive azoospermic male infertility. Gonadotropin treatment can successfully induce spermatogenesis in most patients, although comprehensive quantitative summary data on spermatogenic outcomes like those required to induce pregnancy is lacking in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Systematic review and meta\u2010analysis of outcomes related to male reproductive function following gonadotropin treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our search strategy identified 41 studies encompassing 1673 patients with a mean age of 25 (\u00b1\u20095)\u2009years. Average sperm concentration achieved after a median of 18\u2009months of gonadotropin treatment was 11.6\u2009M\/mL of ejaculate (95% CI 8.4\u201314.9). Sperm concentrations &gt;\u20090, &gt;\u20091, &gt;\u20095, &gt;\u200910 and &gt;\u200920\u2009M\/mL were achieved by 78%, 55%, 36%, 24% and 15% of patients, respectively. Mean sperm output and the proportion of patients achieving all sperm thresholds were significantly greater following combined hCG\/FSH treatment compared with hCG monotherapy. When compared by diagnosis, patients with congenital HH (CHH) had significantly lower mean sperm output compared with patients with hypopituitarism or mixed patient cohorts that did not differentiate between CHH and hypopituitarism. Treatment\u2010related increases in testosterone and testicular volume (TV) were not different between hCG and combined hCG\/FSH treated patients, although increases in TV were lower in men with CHH compared with those with hypopituitarism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gonadotropin treatment successfully induced spermatogenesis in most men with pathological gonadotropin deficiency. Sperm outputs more consistent with those typically needed to induce a natural pregnancy were less commonly achieved. Despite similar effects on serum testosterone and TV, combined hCG\/FSH appeared more efficacious than hCG alone at inducing spermatogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.15151","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T12:49:04Z","timestamp":1729774144000},"page":"167-177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta\u2010Analysis"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1430-0499","authenticated-orcid":false,"given":"Christopher A.","family":"Muir","sequence":"first","affiliation":[{"name":"Department of Andrology Concord Repatriation General Hospital Sydney New South Wales Australia"},{"name":"Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia"},{"name":"School of Clinical Medicine University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Andrology Concord Repatriation General Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Jayadev","sequence":"additional","affiliation":[{"name":"Department of Andrology Concord Repatriation General Hospital Sydney New South Wales Australia"},{"name":"Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann J.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Andrology Concord Repatriation General Hospital Sydney New South Wales Australia"},{"name":"Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Handelsman","sequence":"additional","affiliation":[{"name":"Department of Andrology Concord Repatriation General Hospital Sydney New South Wales Australia"},{"name":"Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia"},{"name":"ANZAC Research Institute Concord Repatriation General Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00459-w"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-18907-1.00141-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00116"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvad166"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2014.10.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1648"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.262"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000002867"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01381-z"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-135"},{"issue":"3","key":"e_1_2_7_12_1","first-page":"40","article-title":"Meta: An R Package for Meta\u2010Analysis","volume":"7","author":"Schwarzer G.","year":"2007","journal-title":"R News"},{"issue":"3","key":"e_1_2_7_13_1","first-page":"113","article-title":"Gonadotropins in Infertile Men With Idiopathic Hypogonadotropic Hypogonadism","volume":"2","author":"Abbasi H.","year":"2008","journal-title":"International Journal of Fertility and Sterility"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(98)00450-6"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2003.tb02712.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1390298"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/12.5.980"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-66-6-1144"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)60084-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-021-01556-x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_107_18"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.108.007278"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(98)00156-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198509123131102"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02550500"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1984.tb03347.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb03785.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1310347"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1994.tb01249.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-61-4-746"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)59720-9"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2021.04.009"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.07.1742"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000158133.09197.f4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-017-0232-y"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/14647271003639723"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_6_19"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12128"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13164"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)54493-8"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)54730-X"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-020-01111-6"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den046"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03346659"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1992.tb01131.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.06.022"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3802"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/1557988318818280"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2023.11.010"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.02315"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180284"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp048"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnae003"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68614-5"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-59-5-882"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111024"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-6-1184"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1985.tb00829.x"},{"issue":"6","key":"e_1_2_7_59_1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1210\/jcem.77.6.8263139","article-title":"Failure of Combined Follicle\u2010Stimulating Hormone\u2013Testosterone Administration to Initiate and\/or Maintain Spermatogenesis in Men With Hypogonadotropic Hypogonadism","volume":"77","author":"Schaison G.","year":"1993","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000508329"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.15151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T13:16:38Z","timestamp":1735823798000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.15151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/cen.15151"],"URL":"https:\/\/doi.org\/10.1111\/cen.15151","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]},"assertion":[{"value":"2024-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}