{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:27Z","timestamp":1787028507311,"version":"build-2736575974"},"reference-count":84,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guzip Biomarkers Corporation and Taipei Medical University collaboration project","award":["A-109-020"],"award-info":[{"award-number":["A-109-020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), na\u00efve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.<\/jats:p>","DOI":"10.3390\/ijms24065598","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"5598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7586-8619","authenticated-orcid":false,"given":"Quang Anh","family":"Do","sequence":"first","affiliation":[{"name":"International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Hai Phong University of Medicine and Pharmacy, Hai Phong 04254, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-6382","authenticated-orcid":false,"given":"Po-Hsuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"},{"name":"Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Dr. Wang Reproductive Fertility Center, Taipei 110007, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-5903","authenticated-orcid":false,"given":"Yi-Xuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"Taipei Fertility Center, Taipei 110016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chun","family":"Weng","sequence":"additional","affiliation":[{"name":"Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-3664","authenticated-orcid":false,"given":"Lin-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"},{"name":"Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Han","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"},{"name":"Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"},{"name":"Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s10815-020-01756-z","article-title":"Impact of contraception and IVF hormones on metabolic, endocrine, and inflammatory status","volume":"37","author":"Coussa","year":"2020","journal-title":"J. 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