{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:10:21Z","timestamp":1756379421750,"version":"3.44.0"},"reference-count":22,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,6,2]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>46,XX male sex reversal syndrome is a rare genetic disorder where individuals with a 46,XX karyotype present with male phenotypic characteristics despite the absence of an Y chromosome. We report a case of a male in his early 30s, presenting with infertility and azoospermia, with bilateral small testes, but no other sexual dysfunction or any signs of hypovirulisation. His hormonal evaluation revealed hypogonadism with normal gonadotropin levels. Genetic testing showed a 46,XX karyotype with the presence of the sex-determining region on the Y chromosome (SRY) gene and microdeletions in the azoospermia factor region, confirming the diagnosis of SRY-positive 46,XX male sex reversal syndrome. As sperm retrieval was not recommended, the couple pursued donor insemination, resulting in conception during the first cycle. The female partner is now in her third trimester of pregnancy. Testosterone replacement therapy was initiated for hypogonadism, and long-term follow-up was recommended for monitoring therapy and neoplastic risk. This case intends to provide an overview focused on improving diagnostic and management strategies for 46,XX male sex reversal syndrome, emphasising the necessity of genetic evaluation for all patients with hypogonadism and azoospermia presenting with infertility, not limited to those with hypergonadotropic hypogonadism. It also highlights the critical role of a multidisciplinary approach in the effective management of this condition.<\/jats:p>","DOI":"10.1136\/bcr-2025-265767","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:29Z","timestamp":1751587229000},"page":"e265767","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Male sex reversal syndrome: a disorder of sexual differentiation (DSD) with infertility"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7755-2391","authenticated-orcid":false,"given":"Namita","family":"Bellad","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine and Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radha","family":"Vembu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monna","family":"Pandurangi","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N Sanjeeva","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"2025082803355386000_18.7.e265767.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32667-2"},{"key":"2025082803355386000_18.7.e265767.2","doi-asserted-by":"crossref","unstructured":"Krausz C , Rosta V , Swerdloff RS , et al . Genetics of male infertility. In: Elsevier ebooks. 2021: 121\u201347. Available: https:\/\/doi.org\/10.1016\/b978-0-12-815236-2.00010-2","DOI":"10.1016\/B978-0-12-815236-2.00010-2"},{"key":"2025082803355386000_18.7.e265767.3","article-title":"XX SEX CHROMOSOMES IN A HUMAN MALE. FIRST CASE","volume":"175","author":"Delachapelle","year":"1964","journal-title":"Acta Med Scand"},{"key":"2025082803355386000_18.7.e265767.4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12301-021-00210-5","article-title":"A rare case of male sex reversal syndrome (46, XX) with negative SRY gene: a disorder of sexual differentiation (DSD)","volume":"27","author":"Abd El Salam","year":"2021","journal-title":"Afr J Urol"},{"key":"2025082803355386000_18.7.e265767.5","first-page":"169","article-title":"Severe XIST hypomethylation clearly distinguishes (SRY+) 46,XX-maleness from Klinefelter syndrome","volume":"162","author":"Poplinski","year":"2010","journal-title":"J Endocrinol"},{"key":"2025082803355386000_18.7.e265767.6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0003-3995(03)00011-X","article-title":"Skewed X-chromosome inactivation pattern in SRY positive XX maleness: a case report and review of literature","volume":"46","author":"Bouayed Abdelmoula","year":"2003","journal-title":"Ann Genet"},{"key":"2025082803355386000_18.7.e265767.7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4103\/jhrs.jhrs_100_22","article-title":"A 46,XX Karyotype in Men with Infertility","volume":"15","author":"Kouvidi","year":"2022","journal-title":"J Hum Reprod Sci"},{"key":"2025082803355386000_18.7.e265767.8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.15605\/jafes.038.02.09","article-title":"Sex Reversal Syndrome (SRS): A Case of SRY-Positive 46,XX Testicular Disorder","volume":"38","author":"Shil","year":"2023","journal-title":"J ASEAN Fed Endocr Soc"},{"key":"2025082803355386000_18.7.e265767.9","doi-asserted-by":"crossref","unstructured":"Rawal L , Prabhash S , Kumar R , et al . 46,XX males with SRY gene translocation: cytogenetics and molecular characterization. J Rare Dis 2024;3. doi:10.1007\/s44162-023-00025-8","DOI":"10.1007\/s44162-023-00025-8"},{"key":"2025082803355386000_18.7.e265767.10","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.7150\/ijms.46058","article-title":"Possible misdiagnosis of 46,XX testicular disorders of sex development in infertile males","volume":"17","author":"Chen","year":"2020","journal-title":"Int J Med Sci"},{"key":"2025082803355386000_18.7.e265767.11","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s10815-013-9939-7","article-title":"Clinical, cytogenetic, and molecular analysis with 46,XX male sex reversal syndrome: case reports","volume":"30","author":"Gao","year":"2013","journal-title":"J Assist Reprod Genet"},{"key":"2025082803355386000_18.7.e265767.12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/BF00196234","article-title":"A possible common origin of \u201cY-negative\u201d human XX males and XX true hermaphrodites","volume":"84","author":"Abbas","year":"1990","journal-title":"Hum Genet"},{"key":"2025082803355386000_18.7.e265767.13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1439-0272.2008.00889.x","article-title":"46, XX male sex reversal syndrome: a case report and review of the genetic basis","volume":"41","author":"Wang","year":"2009","journal-title":"Andrologia"},{"key":"2025082803355386000_18.7.e265767.14","first-page":"924","article-title":"Evaluation of the azoospermic male: AUA\/ASRM guideline","volume":"205","year":"2021","journal-title":"J Urol"},{"key":"2025082803355386000_18.7.e265767.15","first-page":"308","article-title":"46 XX male syndrome with hypogonadotropic hypogonadism: A case report","volume":"6","author":"Yalcin","year":"2019","journal-title":"North Clin Istanb"},{"key":"2025082803355386000_18.7.e265767.16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.933"},{"key":"2025082803355386000_18.7.e265767.17","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s10815-018-1194-5","article-title":"Case of successful IVF treatment of an oligospermic male with 46,XX\/46,XY chimerism","volume":"35","author":"Laursen","year":"2018","journal-title":"J Assist Reprod Genet"},{"key":"2025082803355386000_18.7.e265767.18","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4103\/1008-682X.190329","article-title":"A successful pregnancy by intracytoplasmic sperm injection using ejaculate sperm from an infertile man with 46, XX\/46, XY true hermaphrodite","volume":"19","author":"Sha","year":"2017","journal-title":"Asian J Androl"},{"key":"2025082803355386000_18.7.e265767.19","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh587"},{"key":"2025082803355386000_18.7.e265767.20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s13577-012-0054-3","article-title":"Successful second delivery outcome using refrozen thawed testicular sperm from an infertile male true hermaphrodite with a 46, XX\/46, XY karyotype: case report","volume":"25","author":"Sugawara","year":"2012","journal-title":"Hum Cell"},{"key":"2025082803355386000_18.7.e265767.21","unstructured":"European Association of Urology (EAU) . Male hypogonadism. In: EAU Guidelines. Presented at: EAU Annual Congress. Paris, France, 2024. Available: https:\/\/uroweb.org\/guidelines\/sexual-and-reproductive-health\/chapter\/male-hypogonadism"},{"key":"2025082803355386000_18.7.e265767.22","doi-asserted-by":"crossref","unstructured":"Dicken BJ , Billmire DF , Krailo M , et al . Gonadal dysgenesis is associated with worse outcomes in patients with ovarian nondysgerminomatous tumors: A report of the Children\u2019s Oncology Group AGCT 0132 study. Pediatr Blood Cancer 2018;65. doi:10.1002\/pbc.26913","DOI":"10.1002\/pbc.26913"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2025-265767","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:36:05Z","timestamp":1756377365000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2025-265767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":22,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,3]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bcr-2025-265767"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2025-265767","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}