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We performed a multicenter retrospective cohort study of 50 Japanese women with primary infertility who repeatedly exhibited OZEMA across multiple retrieval cycles. Whole-exome sequencing was used to analyze 24 OZEMA-associated genes, and pathogenic or likely pathogenic variants were classified according to ACMG\/AMP guidelines. Pathogenic or likely pathogenic variants were identified in 10 patients (20%), most frequently in\n                    <jats:italic>TUBB8<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096), followed by\n                    <jats:italic>PATL2<\/jats:italic>\n                    ,\n                    <jats:italic>ZP2<\/jats:italic>\n                    ,\n                    <jats:italic>ZP3<\/jats:italic>\n                    , and\n                    <jats:italic>CHEK1<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091 each). Variant-positive patients had markedly fewer metaphase II oocytes, fertilized oocytes, day-3 embryos, transfer-eligible day-3 embryos, and blastocysts than variant-negative patients. No variant-positive patient achieved a day-3 embryo. Failure to achieve day-3 embryos showed 100% sensitivity and 82.5% specificity for predicting pathogenic or likely pathogenic variants, with higher specificity than failure to achieve transfer-eligible day-3 embryos or blastocysts. These findings characterized OZEMA-associated genetic variants in a Japanese multicenter cohort and suggest that failure to achieve day-3 embryos may help identify patients who require genetic testing.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-60724-2","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:45:20Z","timestamp":1783309520000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene panel analysis for oocyte\/zygote\/embryo maturation arrest in female infertility: a multicenter study in Japan"],"prefix":"10.1038","volume":"16","author":[{"given":"Yusuke","family":"Sako","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Inagaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Nishizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iori","family":"Kisu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-5218","authenticated-orcid":false,"given":"Hiroki","family":"Kurahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"60724_CR1","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.fertnstert.2013.11.004","volume":"101","author":"JM Franasiak","year":"2014","unstructured":"Franasiak, J. 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