{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:12:10Z","timestamp":1785496330331,"version":"3.56.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P50HD071836"],"award-info":[{"award-number":["P50HD071836"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P51 ODO11092"],"award-info":[{"award-number":["P51 ODO11092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Endocrine Technologies Support Core"},{"DOI":"10.13039\/100008143","name":"Oregon National Primate Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008143","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016206","name":"UCLA CTSI","doi-asserted-by":"publisher","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100016206","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Santa Monica Bay Woman\u2019s Club"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Anti-M\u00fcllerian hormone (AMH) is produced by granulosa cells of pre-antral and small antral ovarian follicles. In polycystic ovary syndrome (PCOS), higher levels of serum AMH are usually encountered due to the ample presence of small antral follicles and a high AMH production per follicular unit which have led to the proposal of AMH as a serum diagnostic marker for PCOS or as a surrogate for polycystic ovarian morphology (PCOM). However, heterozygous coding mutations of the AMH gene with decreased in vitro bioactivity have been described in some women with PCOS. Such mutation carriers have a trend toward reduced serum AMH levels compared to noncarriers, although both types of women with PCOS have similar circulating gonadotropin and testosterone (T) levels. This report describes a normal-weight woman with PCOS by NIH criteria with severely reduced AMH levels (index woman with PCOS). Our objective was to examine the molecular basis for her reduced serum AMH levels and to compare her endocrine characteristics to similar-weight women with PCOS and detectable AMH levels. Twenty normoandrogenic ovulatory (control) and 13 age- and BMI-matched women with PCOS (19\u201335 years; 19\u201325 kg\/m2) underwent transvaginal sonography and serum hormone measures including gonadotropins, sex hormone-binding globulin, total and free T, androstenedione, dehydroepiandrosterone sulfate, estrone, estradiol and AMH. The latter was measured by ELISA (Pico-AMH: Ansh Labs, Webster, TX, USA). Women with PCOS and detectable AMH had higher serum AMH (10.82 (6.74\u201313.40) ng\/ml, median (interquartile range)), total and free T (total T: 55.5 (49.5\u201362.5) ng\/dl; free T: 5.65 (4.75\u20136.6) pg\/ml) levels and greater total antral follicle count (AFC) (46 (39\u201359) follicles) than controls (AMH: 4.03 (2.47\u20136.11) ng\/ml; total T: 30 (24.5\u201334.5) ng\/dl; free T: 2.2 (1.8\u20132.45) pg\/ml; AFC 16 (14.5\u201321.5) follicles, P\u2009&amp;lt;\u20090.05, all values), along with a trend toward LH hypersecretion (P\u2009=\u20090.06). The index woman with PCOS had severely reduced serum AMH levels (\u223c0.1 ng\/ml), although she also had a typical NIH-defined PCOS phenotype resembling that of the other women with PCOS and elevated AMH levels. All women with PCOS, including the index woman with PCOS, exhibited LH hypersecretion, hyperandrogenism, reduced serum estrogen\/androgen ratios and PCOM. A homozygous Ala515Val variant (rs10417628) in the mature region of AMH was identified in the index woman with PCOS. Recombinant hAMH-515Val displayed normal processing and bioactivity, yet had severely reduced immunoactivity when measured by the commercial pico-AMH ELISA assay by Ansh Labs. In conclusion, homozygous AMH variant rs10417628 may severely impair serum AMH immunoactivity without affecting its bioactivity or PCOS phenotypic expression. Variants in AMH can interfere with serum AMH immunoactivity without affecting the phenotype in PCOS. This observation can be accompanied by discordance between AMH immunoactivity and bioactivity.<\/jats:p>","DOI":"10.1093\/humrep\/deaa199","type":"journal-article","created":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T19:08:40Z","timestamp":1595704120000},"page":"2294-2302","source":"Crossref","is-referenced-by-count":26,"title":["Loss of anti-M\u00fcllerian hormone (AMH) immunoactivity due to a homozygous AMH gene variant rs10417628 in a woman with classical polycystic ovary syndrome (PCOS)"],"prefix":"10.1093","volume":"35","author":[{"given":"Luis R","family":"Hoyos","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny A","family":"Visser","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"McLuskey","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio D","family":"Chazenbalk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan R","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A","family":"Dumesic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"2020092514445960500_deaa199-B1","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1210\/jc.2006-1066","article-title":"Estradiol and regulation of anti-Mullerian hormone, inhibin-A, and inhibin-B secretion: analysis of small antral and preovulatory human follicles\u2019 fluid","volume":"91","author":"Andersen","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020092514445960500_deaa199-B2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tem.2008.08.002","article-title":"Anti-Mullerian hormone and ovarian dysfunction","volume":"19","author":"Broekmans","year":"2008","journal-title":"Trends Endocrinol Metab"},{"key":"2020092514445960500_deaa199-B3","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1210\/en.2012-1158","article-title":"The role of 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