{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:26:01Z","timestamp":1790342761045,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61973257"],"award-info":[{"award-number":["61973257"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1004203"],"award-info":[{"award-number":["2018YFC1004203"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The microorganisms of the reproductive tract have been implicated to affect <jats:italic>in vitro<\/jats:italic> fertilization (IVF) outcomes. However, studies on the reproductive tract microbiota of infertile women are limited and the correlation between cervical microbiota and IVF outcome remains elusive. This study aimed to characterize the cervical microbiota of IVF patients undergoing embryo transfer (ET) and assess associations between the cervical microbiota and pregnancy outcomes while exploring the underlying contributing factors. We launched a nested case-control study of 100 patients with two fresh or frozen-thawed cleavage embryos transferred per IVF cycle. Cervical swabs were collected on the day of ET and divided into four groups according to clinical pregnancy outcomes. Variable regions 3 and 4 (V3-V4) of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. In fresh IVF-ET cycles, the clinical pregnancy group (FP, n = 25) demonstrated higher \u03b1 diversity (<jats:italic>P<\/jats:italic> = 0.0078) than the non-pregnancy group (FN, n = 26). Analysis of similarity (ANOSIM) revealed a significant difference in \u03b2 diversity between the two groups (R = 0.242, <jats:italic>P<\/jats:italic> = 0.001). In frozen-thawed ET cycles, though not significant, similar higher \u03b1 diversity was found in the clinical pregnancy group (TP, n = 27) compared to the non-pregnancy group (TN, n = 22) and ANOSIM analysis showed a significant difference between the two groups (R = 0.062, <jats:italic>P<\/jats:italic> = 0.045). For patients in fresh IVF-ET groups, <jats:italic>Lactobacillus<\/jats:italic>, <jats:italic>Akkermansia<\/jats:italic>, <jats:italic>Desulfovibrio<\/jats:italic>, <jats:italic>Atopobium<\/jats:italic>, and <jats:italic>Gardnerella<\/jats:italic> showed differentially abundance between pregnant and non-pregnant women and they accounted for the largest share of all taxa investigated. Among them, <jats:italic>Lactobacillus<\/jats:italic> was negatively correlated with the other genera and positively correlated with serum estradiol levels. Logistic regression analysis suggested that the composition of the cervical microbiota on the day of ET was associated with the clinical pregnancy in fresh IVF-ET cycles (<jats:italic>P<\/jats:italic> = 0.030). Our results indicate that cervical microbiota composition has an impact on the outcome of assisted reproductive therapy.<\/jats:p>","DOI":"10.3389\/fcimb.2021.654202","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T07:00:20Z","timestamp":1632380420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Association of the Cervical Microbiota With Pregnancy Outcome in a Subfertile Population Undergoing In Vitro Fertilization: A Case-Control Study"],"prefix":"10.3389","volume":"11","author":[{"given":"Xinyao","family":"Hao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.29769","article-title":"Drug-Eluting Endotracheal Tubes for Preventing Bacterial Inflammation in Subglottic Stenosis","author":"Aronson","year":"2021","journal-title":"Laryngoscope"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1007\/s10815-019-01564-0","article-title":"Effect of the Vaginal Microbiome on the Pregnancy Rate in Women Receiving Assisted Reproductive Treatment","volume":"36","author":"Bernabeu","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/S1286-4579(00)00313-0","article-title":"Role Played by Lactobacilli in Controlling the Population of Vaginal Pathogens","volume":"2","author":"Boris","year":"2000","journal-title":"Microbes Infect."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1093\/humrep\/deh314","article-title":"Investigation of the Infertile Couple: When is the Appropriate Time to Explore Female Infertility","volume":"19","author":"Brosens","year":"2004","journal-title":"Hum. Reprod."},{"key":"B5","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/s41467-017-00901-0","article-title":"The Microbiota Continuum Along the Female Reproductive Tract and its Relation to Uterine-Related Diseases","volume":"8","author":"Chen","year":"2017","journal-title":"Nat. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization Reference Values for Human Semen Characteristics","volume":"16","author":"Cooper","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"B7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/prd.12296","article-title":"The Role of the Microbiota in Periodontal Disease","volume":"83","author":"Curtis","year":"2020","journal-title":"Periodontol. 2000"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.beem.2019.01.004","article-title":"Assisted Reproductive Technology: Impact on Society and Need for Surveillance","volume":"33","author":"De Geyter","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1093\/humrep\/den132","article-title":"Pregnancy Chances on an IVF\/ICSI Waiting List: A National Prospective Cohort Study","volume":"23","author":"Eijkemans","year":"2008","journal-title":"Hum. Reprod."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-019-09285-9","article-title":"Cervicovaginal Microbiota and Local Immune Response Modulate the Risk of Spontaneous Preterm Delivery","volume":"10","author":"Elovitz","year":"2019","journal-title":"Nat. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"226.e1","DOI":"10.1016\/j.ajog.2013.10.003","article-title":"Mycoplasma, Bacterial Vaginosis-Associated Bacteria BVAB3, Race, and Risk of Preterm Birth in a High-Risk Cohort","volume":"210","author":"Foxman","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003605","article-title":"Temporal Dynamics of the Human Vaginal Microbiota","volume":"4","author":"Gajer","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.rbmo.2017.04.005","article-title":"What Fertility Specialists Should Know About the Vaginal Microbiome: A Review","volume":"35","author":"Garc\u00eda-Velasco","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"B14","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1111\/1471-0528.15178","article-title":"And Humaidan, P","volume":"126","author":"Haahr","year":"2019","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1007\/s10815-019-01630-7","article-title":"Does Dysbiotic Endometrium Affect Blastocyst Implantation in IVF Patients","volume":"36","author":"Hashimoto","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s10815-011-9694-6","article-title":"The Dynamics of the Vaginal Microbiome During Infertility Therapy With In Vitro Fertilization-Embryo Transfer","volume":"29","author":"Hyman","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2021.01.005","article-title":"Life History Recorded in the Vagino-Cervical Microbiome Along With Multi-Omics","author":"Jie","year":"2021","journal-title":"Genomics Proteomics Bioinf"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1093\/humrep\/dez065","article-title":"The Vaginal Microbiome as a Predictor for Outcome of In Vitro Fertilization With or Without Intracytoplasmic Sperm Injection: A Prospective Study","volume":"34","author":"Koedooder","year":"2019","journal-title":"Hum. Reprod."},{"key":"B19","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/rmb2.12250","article-title":"A Pilot Study and Case Reports on Endometrial Microbiota and Pregnancy Outcome: An Analysis Using 16S rRNA Gene Sequencing Among IVF Patients, and Trial Therapeutic Intervention for Dysbiotic Endometrium","volume":"18","author":"Kyono","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.fertnstert.2019.05.015","article-title":"Endometrial Microbiota in Infertile Women With and Without Chronic Endometritis as Diagnosed Using a Quantitative and Reference Range-Based Method","volume":"112","author":"Liu","year":"2019","journal-title":"Fertil. Steril."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1093\/humrep\/14.9.2411","article-title":"The Influence of Bacterial Vaginosis on in-Vitro Fertilization and Embryo Implantation During Assisted Reproduction Treatment","volume":"14","author":"Liversedge","year":"1999","journal-title":"Hum. Reprod."},{"key":"B22","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s10096-012-1770-z","article-title":"Molecular Diagnosis of Bacterial Vaginosis: Impact on IVF Outcome","volume":"32","author":"Mangot-Bertrand","year":"2013","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1001356","article-title":"National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys","volume":"9","author":"Mascarenhas","year":"2012","journal-title":"PloS Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/978-3-319-31248-4_6","article-title":"Vaginal Microbiota","volume":"902","author":"Mendling","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"611.e1","DOI":"10.1016\/j.ajog.2014.11.043","article-title":"Colonization of the Upper Genital Tract by Vaginal Bacterial Species in Nonpregnant Women","volume":"212","author":"Mitchell","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.ajog.2016.09.075","article-title":"Evidence That the Endometrial Microbiota has an Effect on Implantation Success or Failure","volume":"215","author":"Moreno","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1177\/1933719115581000","article-title":"\u03b1-Amylase in Vaginal Fluid: Association With Conditions Favorable to Dominance of Lactobacillus","volume":"22","author":"Nasioudis","year":"2015","journal-title":"Reprod. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1016\/j.fertnstert.2007.01.035","article-title":"First Trimester Bacterial Vaginosis, Individual Microorganism Levels, and Risk of Second Trimester Pregnancy Loss Among Urban Women","volume":"88","author":"Nelson","year":"2007","journal-title":"Fertil. Steril."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0080074","article-title":"Vaginal pH and Microbicidal Lactic Acid When Lactobacilli Dominate the Microbiota","volume":"8","author":"O\u2019Hanlon","year":"2013","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1186\/1471-2164-15-1070","article-title":"Comparative Genomics of Lactobacillus Crispatus Suggests Novel Mechanisms for the Competitive Exclusion of Gardnerella Vaginalis","volume":"15","author":"Ojala","year":"2014","journal-title":"BMC Genomics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.copbio.2018.01.018","article-title":"Systems Biology of the Human Microbiome","volume":"51","author":"Pe\u00f1alver Bernab\u00e9","year":"2018","journal-title":"Curr. Opin. Biotechnol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1136\/bmj.319.7204.220","article-title":"Influence of Bacterial Vaginosis on Conception and Miscarriage in the First Trimester: Cohort Study","volume":"319","author":"Ralph","year":"1999","journal-title":"BMJ"},{"key":"B33","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.tem.2016.04.004","article-title":"Cervicovaginal Microbiomes-Threats and Possibilities","volume":"27","author":"Reid","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.17660\/ActaHortic.2002.590.48","article-title":"Lactic Acid Permeabilizes Gram-Negative Bacteria by Disrupting the Outer Membrane","volume":"137","author":"Rosell\u00f3","year":"2013","journal-title":"Eur. J. Plant Pathol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1097\/GCO.0000000000000626","article-title":"The Vaginal Microbiome as a Tool to Predict IVF Success","volume":"32","author":"Schoenmakers","year":"2020","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1007\/s00404-011-1857-2","article-title":"Effective of Metronidazole to Bacterial Flora in Vagina and the Impact of Microbes on Live Birth Rate During Intracytoplasmic Sperm Injection (ICSI)","volume":"284","author":"Selim","year":"2011","journal-title":"Arch. Gynecol. Obstet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jogoh.2019.01.007","article-title":"The Relation of the Vaginal Microbiota to Early Pregnancy Development During In Vitro Fertilization Treatment\u2014A Meta-Analysis","volume":"48","author":"Singer","year":"2019","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/microorganisms9061299","article-title":"Diversity and Adaptations of Escherichia Coli Strains: Exploring the Intestinal Community in Crohn\u2019s Disease Patients and Healthy Individuals","volume":"9","author":"Siniagina","year":"2021","journal-title":"Microorganisms"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1093\/infdis\/jiu231","article-title":"Human \u03b1-Amylase Present in Lower-Genital-Tract Mucosal Fluid Processes Glycogen to Support Vaginal Colonization by Lactobacillus","volume":"210","author":"Spear","year":"2014","journal-title":"J. Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.rbmo.2018.12.019","article-title":"Vaginal Microbiota Profile at the Time of Embryo Transfer Does Not Affect Live Birth Rate in IVF Cycles With Donated Oocytes","volume":"38","author":"Vergaro","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"B41","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/ajo.12754","article-title":"A Retrospective Pilot Study to Determine Whether the Reproductive Tract Microbiota Differs Between Women With a History of Infertility and Fertile Women","volume":"58","author":"Wee","year":"2018","journal-title":"Aust. New Zeal. J. Obstet. Gynaecol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12941-020-00356-0","article-title":"Microbiota Composition and Distribution Along the Female Reproductive Tract of Women With Endometriosis","volume":"19","author":"Wei","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.110965","article-title":"Associations of Toxic and Essential Trace Elements in Serum, Follicular Fluid, and Seminal Plasma With In Vitro Fertilization Outcomes","volume":"204","author":"Wu","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/mSystems.00450-20","article-title":"Characterization of the Vaginal Microbiome in Women With Stimulation During In Vitro Fertilization Surgery","volume":"5","author":"Zhao","year":"2020","journal-title":"mSystems"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.654202\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T07:00:22Z","timestamp":1632380422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.654202\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,23]]},"references-count":44,"alternative-id":["10.3389\/fcimb.2021.654202"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.654202","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,23]]},"article-number":"654202"}}