{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:26:34Z","timestamp":1790342794724,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":70,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K08812"],"award-info":[{"award-number":["23K08812"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reprod Medicine &amp; Biology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In the context of in\u00a0vitro fertilization\u2013embryo transfer (IVF\u2013ET), factors other than egg quality may be key determinants of treatment success, in particular, maternal factors related to uterine endometrial receptivity and unidentified factors. We therefore aimed to analyze the metabolome and microbiome in IVF\u2013ET patients who did and did not achieve pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cervicovaginal mucus was collected from patients undergoing IVF\u2013ET. Metabolite analysis was conducted by liquid chromatography\u2010mass spectrometry and the microbiota were determined by the polymerase chain reaction using universal 16S\u2010rRNA gene bacterial primers by MiSeq sequencing. Patients were classified as pregnant (<jats:italic>N<\/jats:italic>\u2009=\u200910) or nonpregnant (<jats:italic>N<\/jats:italic>\u2009=\u200913). Metabolic pathways were examined by MetaboAnalyst.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three metabolic pathways, including alanine\u2010aspartate\u2013glutamate metabolism, arginine biosynthesis, and cysteine\u2010methionine metabolism, were commonly decreased at the time of embryo transfer irrespective pregnant outcomes. Notably, pyruvate was decreased in the pregnant group. Amino acid metabolites showed inverse correlations with the presence of anaerobic microbiota in the nonpregnant group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Metabolism decreased during embryo transplantation, with a notable decrease in pyruvate metabolism, particularly in patients who became pregnant. The behavior of metabolites in the pregnant and nonpregnant groups suggests that metabolome analysis in the cervicovaginal mucus may be a diagnostic marker for predicting pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/rmb2.12568","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T04:51:07Z","timestamp":1710219067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolomic and microbiome analysis of cervicovaginal mucus in in\u00a0vitro fertilization\u2013embryo transfer: Toward predicting pregnancy success"],"prefix":"10.1002","volume":"23","author":[{"given":"Eiji","family":"Nishio","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University, School of Medicine  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University, School of Medicine  Toyoake Aichi Japan"},{"name":"Department of Gynecology Fujita Health University Okazaki Medical Center  Okazaki Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University, School of Medicine  Toyoake Aichi Japan"},{"name":"Department of Gynecology Fujita Health University Okazaki Medical Center  Okazaki Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwao","family":"Kukimoto","sequence":"additional","affiliation":[{"name":"Pathogen Genomics Center National Institute of Infectious Diseases  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University, School of Medicine  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-8663","authenticated-orcid":false,"given":"Takuma","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University, School of Medicine  Toyoake Aichi Japan"},{"name":"Department of Gynecology Fujita Health University Okazaki Medical Center  Okazaki Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12494"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11040376"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224682"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14174"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2021.12.014"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12389"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12495"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010622"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934324"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)58097-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.13095"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.319"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2021.03.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.12.015"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00926-21"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51420"},{"issue":"5","key":"e_1_2_9_18_1","first-page":"437","article-title":"Anaerobic 4\u2010hydroxyproline utilization: discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity","volume":"9","author":"Huang YY","year":"2018","journal-title":"Gut Microbes"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.048"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19-00855"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11040870"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1539-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem253"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10137"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.899485"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20143744"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a138453"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01204436"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioac038"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16782"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11250-019-02022-w"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000690"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13291"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00204-15"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-45328-2_7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-021-00259-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03242-19"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew064"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev008"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz042"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx023"}],"container-title":["Reproductive Medicine and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmb2.12568","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T14:43:05Z","timestamp":1736174585000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmb2.12568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/rmb2.12568"],"URL":"https:\/\/doi.org\/10.1002\/rmb2.12568","archive":["Portico"],"relation":{},"ISSN":["1445-5781","1447-0578"],"issn-type":[{"value":"1445-5781","type":"print"},{"value":"1447-0578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12568"}}