{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:29Z","timestamp":1784700389438,"version":"3.55.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aims to explore the clinical characteristics, genetic etiology, and individualized treatment strategies of patients with PCOS complicated by oocyte maturation disorders caused by novel compound heterozygous variants of the\n                      <jats:italic>PATL2<\/jats:italic>\n                      gene, and to expand the mutation and phenotypic spectrum of the\n                      <jats:italic>PATL2<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data and two cycles of controlled ovarian hyperstimulation (COH) were collected from a 34-year-old patient with primary infertility and PMOS. Genetic analysis was performed using whole-exome sequencing (WES), and variant pathogenicity was predicted by bioinformatics tools. An individualized COH protocol was designed and implemented based on the genetic diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient had 8\u202fyears of primary infertility. In the first cycle, 10 oocytes were retrieved after COH with an antagonist protocol, all arrested at the germinal vesicle (GV) stage. WES revealed compound heterozygous variants in the PATL2 gene (OMIM: 617743): NM_001145112.1: c.1225-2A\u202f&amp;gt;\u202fG (splice-site variant) and c.1382\u202fT\u202f&amp;gt;\u202fC (p.Leu461Pro, missense variant), consistent with autosomal recessive inheritance. Both variants were predicted to be deleterious, and c.1382\u202fT\u202f&amp;gt;\u202fC was a novel unreported variant. In the second cycle, a long follicular protocol, delayed trigger, segmented oocyte retrieval, and indomethacin for spontaneous ovulation prevention were applied. A total of 24 oocytes were retrieved; however, all remained arrested at the GV stage after\n                      <jats:italic>in vitro<\/jats:italic>\n                      culture, and no mature oocytes were obtained.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Compound heterozygous variants c.1225-2A\u202f&amp;gt;\u202fG and c.1382\u202fT\u202f&amp;gt;\u202fC in\n                      <jats:italic>PATL2<\/jats:italic>\n                      are the core genetic cause of GV-stage oocyte arrest in this patient. GV arrest caused by\n                      <jats:italic>PATL2<\/jats:italic>\n                      defects cannot be overcome by conventional or optimized IVF protocols even with individualized COH. WES provides critical evidence for etiological clarification, avoidance of ineffective treatment, and genetic counseling. Donor-oocyte IVF remains the ultimate effective strategy for pregnancy in such patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1891656","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:44Z","timestamp":1784699564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Compound heterozygous variants in PATL2 cause oocyte germinal vesicle arrest associated with primary infertility: a case report and literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoxia","family":"Song","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Women\u2019s and Children\u2019s Hospital Affiliated to Dalian University of Technology","place":["Dalian, Liaoning, China"]},{"name":"Dalian Women and Children\u2019s Medical Group","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yan","sequence":"additional","affiliation":[{"name":"Dalian Women and Children\u2019s Medical Group","place":["Dalian, Liaoning, China"]},{"name":"Reproductive Medicine Laboratory, Women\u2019s and Children\u2019s Hospital Affiliated to Dalian University of Technology","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Women\u2019s and Children\u2019s Hospital Affiliated to Dalian University of Technology","place":["Dalian, Liaoning, China"]},{"name":"Dalian Women and Children\u2019s Medical Group","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Women\u2019s and Children\u2019s Hospital Affiliated to Dalian University of Technology","place":["Dalian, Liaoning, China"]},{"name":"Dalian Women and Children\u2019s Medical Group","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"13002","DOI":"10.3390\/ijms252313002","article-title":"Genetic abnormalities of oocyte maturation: mechanisms and clinical implications","volume":"25","author":"Baldini","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1007\/s10815-024-03195-6","article-title":"Genetic factors of oocyte maturation arrest: an important cause for recurrent IVF\/ICSI failures","volume":"41","author":"Wang","year":"2024","journal-title":"J Assist Reprod Genet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1007\/s10815-024-03150-5","article-title":"Novel PATL2 variants cause female infertility with oocyte maturation defect","volume":"41","author":"Hu","year":"2024","journal-title":"J Assist Reprod Genet"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s10815-020-01698-9","article-title":"Novel homozygous mutations in PATL2 lead to female infertility with oocyte maturation arrest","volume":"37","author":"Liu","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1611138","DOI":"10.3389\/fgene.2025.1611138","article-title":"Identification of a PATL2 missense variant (c.877G>T) disrupting canonical splicing and contributing to female infertility","volume":"16","author":"Li","year":"2025","journal-title":"Front Genet"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1007\/s10815-024-03071-3","article-title":"Identification novel mutations and phenotypic spectrum expanding in PATL2 in infertile women with IVF\/ICSI failure","volume":"41","author":"Ye","year":"2024","journal-title":"J Assist Reprod Genet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1093\/humrep\/dey100","article-title":"Novel mutations in PATL2 cause female infertility with oocyte germinal vesicle arrest","volume":"33","author":"Huang","year":"2018","journal-title":"Hum 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lipid metabolism on oocytes and the potential metabolic imbalance in polycystic ovary syndrome","volume":"24","author":"Zhang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1007\/s43032-023-01420-8","article-title":"Reduced PATL2 impairs the proliferation of ovarian granulosa cells by decreasing ADM2 expression in patients with PMOS","volume":"31","author":"Tan","year":"2024","journal-title":"Reprod Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1080\/09513590.2021.1928066","article-title":"PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PMOS","volume":"37","author":"Peng","year":"2021","journal-title":"Gynecol Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"5877","DOI":"10.1210\/jc.2019-01276","article-title":"Pregnancy and live birth in women with pathogenic LHCGR variants using their own oocytes","volume":"104","author":"Lu","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1093\/humupd\/dmad007","article-title":"Total fertilization failure after ICSI: insights into pathophysiology, diagnosis, and management through artificial oocyte activation","volume":"29","author":"Campos","year":"2023","journal-title":"Hum Reprod Update"}],"container-title":["Frontiers in 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