{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:32:02Z","timestamp":1777984322126,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.166812.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000}}],"reference-count":43,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HIBAH PUTI 2024 Universitas Indonesia","award":["NKB-289\/UN2.RST\/HKP.05.00\/2024"],"award-info":[{"award-number":["NKB-289\/UN2.RST\/HKP.05.00\/2024"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns7:p>Objective This study aims to evaluate spermatogenic failure in azoospermic men by characterizing patterns in Modified Johnsen Scores from testicular biopsies, examining their correlation with clinical and hormonal parameters, and determining the probability of live sperm retrieval. Novelty As one of the largest datasets on azoospermia in Indonesia, this study provides a comprehensive histopathological and hormonal profile of azoospermic patients, while also emphasizing the diagnostic value of bilateral testicular biopsies\u2014an area often underexplored in Southeast Asian populations. Methods A retrospective analysis was conducted on azoospermic patients who underwent bilateral testicular biopsies between April 2011 and July 2024. Testicular tissue samples were assessed using the Modified Johnsen scoring system (range: 1 to 10), and classified histopathologically from tubular fibrosis to complete spermatogenesis. Clinical parameters, including age, body mass index, sperm retrieval outcomes, and serum levels of follicle-stimulating hormone, luteinizing hormone, and testosterone, were collected and analyzed. Statistical associations between these parameters and histopathological subtypes were determined using significance testing. Results A total of 409 testicular biopsies were evaluated. The most frequent Modified Johnsen Scores were 7 (20%) and 5 (16.6%). Histopathological analysis showed that 40.3% of cases exhibited spermatogenic arrest, while only 7% demonstrated normal spermatogenesis. Discordant histopathological patterns between the two testes were observed in 18.5% of patients. Follicle-stimulating hormone and luteinizing hormone levels showed statistically significant associations with histopathological subtypes (p &lt; 0.001). Age, body mass index, and testosterone levels did not correlate significantly. Conclusion Spermatogenic arrest is the predominant abnormality in azoospermic men, with hormonal variations\u2014particularly in follicle-stimulating hormone and luteinizing hormone\u2014strongly associated with testicular pathology. The discordant histology between the testes underscores the importance of bilateral biopsies. Higher Modified Johnsen Scores were positively correlated with the likelihood of successful sperm retrieval.<\/ns7:p>","DOI":"10.12688\/f1000research.166812.2","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:44:08Z","timestamp":1773827048000},"page":"25","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering fertility potential: Clinical and histopathological insights from testicular biopsies in azoospermic men in a large Indonesian cohort"],"prefix":"10.12688","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-2713","authenticated-orcid":false,"given":"Dyandra","family":"Parikesit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-0610","authenticated-orcid":false,"given":"Armand","family":"Achmadsyah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Favian Ariiq","family":"Rahmat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8076-8586","authenticated-orcid":false,"given":"Retta Catherina","family":"Sihotang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heri","family":"Wibowo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aria","family":"Kekalih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luluk","family":"Yunaini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmarinah","family":".","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-3668","authenticated-orcid":false,"given":"Eric","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-6753","authenticated-orcid":false,"given":"Ponco","family":"Birowo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"15-26","DOI":"10.6061\/clinics\/2013(Sup01)03","article-title":"The epidemiology and etiology of azoospermia.","volume":"68","author":"M Cocuzza","year":"2013","journal-title":"Clinics."},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.32421\/juri.v23i2.251","article-title":"ETIOLOGY OF MALE INFERTILITY IN JAKARTA.","volume":"23","author":"A Basukarno","year":"2016 Sept","journal-title":"Indones J. 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Endocrinol."},{"key":"ref9","first-page":"81-86","article-title":"Histopathological Patterns of Testicular Biopsies in Male Infertility.","volume":"2","author":"H Mushtaq","year":"2013","journal-title":"J. Islamabad Med. Dent. Coll."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"346-355","DOI":"10.21037\/tau.2019.06.23","article-title":"Cut-off values of the Johnsen score and Copenhagen index as histopathological prognostic factors for postoperative semen quality in selected infertile patients undergoing microsurgical correction of bilateral subclinical varicocele.","volume":"8","author":"T Teixeira","year":"2019 Aug","journal-title":"Transl. Androl. Urol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/ijerph21050517","article-title":"The Association between Body Mass Index and Glycohemoglobin (HbA1c) in the US Population\u2019s Diabetes Status.","volume":"21","author":"W Lin","year":"2024 Apr 23","journal-title":"Int. J. Environ. Res. Public Health."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1186\/s12889-023-16793-3","article-title":"Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of global burden of disease study.","volume":"23","author":"B Huang","year":"2023 Nov 8","journal-title":"BMC Public Health."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"S206-S214","DOI":"10.21037\/tau.2019.08.36","article-title":"Towards a better testicular sperm extraction: novel sperm sorting technologies for non-motile sperm extracted by microdissection TESE.","volume":"9","author":"C Mangum","year":"2020 Mar","journal-title":"Transl. Androl. Urol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1764-1770","DOI":"10.1111\/andr.13610","article-title":"Testicular biopsies in men with testicular microlithiasis and additional risk factors for cancer: A case series.","volume":"12","author":"R Frandsen","year":"2024 Nov","journal-title":"Andrology."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"555-593","DOI":"10.1016\/S0094-0143(05)70200-7","article-title":"TESTICULAR BIOPSY.","volume":"26","author":"M Nistal","year":"1999 Aug","journal-title":"Urol. Clin. North Am."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"19-23","DOI":"10.4103\/0974-7796.75867","article-title":"Histopathological patterns of testicular biopsy in male infertility: A retrospective study from a tertiary care center in the western part of Saudi Arabia.","volume":"3","author":"L Abdullah","year":"2011","journal-title":"Urol. 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J."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"577-581","DOI":"10.1136\/bmj.3.5880.577","article-title":"Testicular Biopsy in Evaluation of Male Infertility.","volume":"3","author":"E Meinhard","year":"1973 Sept 15","journal-title":"BMJ."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.5580\/16b2","article-title":"Patterns of Testicular Histopathology in Men with Primary Infertility.","volume":"5","author":"M Rashed","year":"2008","journal-title":"Int. J. Urol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"56-60","DOI":"10.1016\/S0015-0282(16)44479-1","article-title":"Reappraisal of the Value of Testicular Biopsy in the Investigation of Infertility.","volume":"33","author":"T Colgan","year":"1980 Jan","journal-title":"Fertil. Steril."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"147-150","DOI":"10.1159\/000325923","article-title":"Testicular Fine Needle Aspiration Cytology in Male Infertility.","volume":"50","author":"A Amin","year":"2006","journal-title":"Acta. Cytol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"757-762","DOI":"10.1016\/S0022-5347(17)56589-1","article-title":"Testicular Abnormalities of the Subfertile Male.","volume":"122","author":"G Brannen","year":"1979 Dec","journal-title":"J Urol."},{"key":"ref24","first-page":"992-994","article-title":"Morphological profile of testicular biopsies associated with infertility.","volume":"22","author":"A Jamal","year":"2001 Nov","journal-title":"Saudi Med. J."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"177-182","DOI":"10.30699\/ijp.2017.25036","article-title":"Testicular Biopsy in Males With Infertility: A Longitudinal Study.","volume":"12","author":"S Siadati","year":"2017","journal-title":"Iran J. Pathol."},{"key":"ref26","first-page":"625-628","article-title":"Morphologic patterns of male infertility in Saudi patients. A University Hospital experience.","volume":"21","author":"M Al-Rayess","year":"2000 July","journal-title":"Saudi Med. J."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"978-983","DOI":"10.1016\/S0015-0282(16)53990-9","article-title":"The prevalence of subfertility: a review of the current confusion and a report of two new studies.","volume":"54","author":"E Greenhall","year":"1990 Dec","journal-title":"Fertil. Steril."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"477-482","DOI":"10.1590\/S1415-47572004000400002","article-title":"Somatic and germ cell cytogenetic studies and AZF microdeletion screening in infertile men.","volume":"27","author":"R Carrara","year":"2004","journal-title":"Genet. Mol. 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Androl."},{"key":"ref32","first-page":"578-584","article-title":"Histological pattern of testicular biopsies in infertile males in Ibadan.","volume":"67","author":"J Thomas","year":"1990 Aug","journal-title":"Nigeria. East Afr. Med. J."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1442-1456","DOI":"10.21037\/tau.2020.03.35","article-title":"Histology and sperm retrieval among men with Y chromosome microdeletions.","volume":"10","author":"W Yuen","year":"2021 Mar","journal-title":"Transl. Androl. Urol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"287-293","DOI":"10.4103\/UA.UA_36_18","article-title":"Microdissection testicular sperm extraction: Overall results and impact of preoperative testosterone level on sperm retrieval rate in patients with nonobstructive azoospermia.","volume":"11","author":"S Mehmood","year":"2019","journal-title":"Urol. 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Steril."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1020-1027","DOI":"10.1111\/andr.12246","article-title":"Micro RNA expression profiles in testicular biopsies of patients with impaired spermatogenesis.","volume":"4","author":"P Noveski","year":"2016 Nov","journal-title":"Andrology."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"915-921","DOI":"10.1016\/j.fertnstert.2020.10.005","article-title":"Efficacy of the second micro\u2013testicular sperm extraction after failed first micro\u2013testicular sperm extraction in men with nonobstructive azoospermia.","volume":"115","author":"O \u00d6zman","year":"2021 Apr","journal-title":"Fertil. Steril."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3015-3018","DOI":"10.1007\/s10815-021-02313-y","article-title":"FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia.","volume":"38","author":"P Kavoussi","year":"2021 Nov","journal-title":"J. Assist Reprod. Genet."},{"key":"ref39","first-page":"e14546","article-title":"Correlation between serum levels of reproductive hormones and testicular spermatogenic function in men with azoospermia.","volume":"54","author":"Y Liu","year":"2022 Nov","journal-title":"Andrologia."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"9-15","DOI":"10.1016\/j.androl.2019.06.001","article-title":"Relationship between testicular histopathology and the success of testicular sperm extraction in patients with non-mosaic Klinefelter syndrome.","volume":"19","author":"C Y\u00fccel","year":"2021 Jan","journal-title":"Rev. Int. 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Med."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"6-12","DOI":"10.1111\/bju.16205","article-title":"Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review.","volume":"134","author":"Z Jiao","year":"2024 July","journal-title":"BJU Int."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/15-25\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/15-25\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/15-25\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T04:59:07Z","timestamp":1773896347000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/15-25\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":43,"URL":"https:\/\/doi.org\/10.12688\/f1000research.166812.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.166812.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.197124.r468660","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.197124.r468660","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/15-25\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.183856.r450727, Doddy Moesbadianto Soebadi, Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 06 Feb 2026, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/15-25\/v1#referee-response-450727","order":0,"name":"referee-response-450727","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.197124.r468660, Hideyuki Kobayashi, Department of Urology, Toho University faculty of Medicine, Tokyo, 19 Mar 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/15-25\/v2#referee-response-468660","order":1,"name":"referee-response-468660","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by HIBAH PUTI 2024 Universitas Indonesia NKB-289\/UN2.RST\/HKP.05.00\/2024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}