{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:34:27Z","timestamp":1791326067131,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:00:00Z","timestamp":1608854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC 26\/13"],"award-info":[{"award-number":["RC 26\/13"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Infertile couples undergoing the use of assisted reproductive technology are a good study model to evaluate the microbiological signatures affecting reproductive health. We tested vaginal lavages, follicular fluids, embryo culture mediums, and seminal fluids from 47 couples for their microbiome composition and HPV infection. Twenty-five infertile couples were diagnosed with unexplained infertility, whereas 22 were diagnosed with explained infertility. Lactobacilli were dominant in the vaginal lavages of both patient groups, and the most abundant species was L. iners (CST III), which is linked to a decreased fertility rate. Besides this, L. gasseri\u2014which is known to be associated with oocyte DNA fragmentation and decreased sperm mobility\u2014was identified in the seminal fluids, follicular fluids, and embryo culture media of the unexplained infertility group. Prevotella was increased in the seminal fluids of the explained infertility group, along with HPV-positive seminal fluids: an infection commonly associated with infertility, especially male infertility. Prevotella has been described to negatively affect sperm motility. Taken together, these results suggest that the profiling of the reproductive tract microbiome can add new perspectives to human reproduction.<\/jats:p>","DOI":"10.3390\/microorganisms9010039","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T22:56:45Z","timestamp":1608850605000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Lactobacillus iners and gasseri, Prevotella bivia and HPV Belong to the Microbiological Signature Negatively Affecting Human Reproduction"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-5537","authenticated-orcid":false,"given":"Giuseppina","family":"Campisciano","sequence":"first","affiliation":[{"name":"Advanced Laboratory of Translational Microbiology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-306X","authenticated-orcid":false,"given":"Valerio","family":"Iebba","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University Hospital of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7836-4934","authenticated-orcid":false,"given":"Gabriella","family":"Zito","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Luppi","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Fischer","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Seta","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University Hospital of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"},{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-4223","authenticated-orcid":false,"given":"Giuseppe","family":"Basile","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Clinical Institute San Siro, Via Monreale 18, 20148 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-1102","authenticated-orcid":false,"given":"Giuseppe","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University Hospital of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"},{"name":"Obstetrics and Gynecology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manola","family":"Comar","sequence":"additional","affiliation":[{"name":"Advanced Laboratory of Translational Microbiology, Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, Via dell\u2019Istria 65, 34137 Trieste, Italy"},{"name":"Department of Medical, Surgical and Health Sciences, University Hospital of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/humrep\/der108","article-title":"Microbial colonization of follicular fluid: Alterations in cytokine expression and adverse assisted reproduction technology outcomes","volume":"26","author":"Pelzer","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.fertnstert.2015.10.010","article-title":"Gynecologic health and disease in relation to the microbiome of the female reproductive tract","volume":"104","author":"Green","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.fertnstert.2015.10.012","article-title":"Reproductive tract microbiome in assisted reproductive technologies","volume":"104","author":"Franasiak","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Graspeuntner, S., Bohlmann, M.K., Gillmann, K., Speer, R., Kuenzel, S., Mark, H., Hoellen, F., Lettau, R., Griesinger, G., and Konig, I.R. (2018). Microbiota-based analysis reveals specific bacterial traits and a novel strategy for the diagnosis of infectious infertility. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191047"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3389\/fcimb.2020.00350","article-title":"Structural variations of vaginal and endometrial microbiota: Hints on female infertility","volume":"10","author":"Riganelli","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","first-page":"534","article-title":"Vaginal lactobacilli profile in pregnant women with normal & abnormal vaginal flora","volume":"146","author":"Yeruva","year":"2017","journal-title":"Indian J. Med. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/humupd\/dmy048","article-title":"Identification and evaluation of the microbiome in the female and male reproductive tracts","volume":"25","author":"Koedooder","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.fertnstert.2013.07.1991","article-title":"Microbiota of the seminal fluid from healthy and infertile men","volume":"100","author":"Hou","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12838","DOI":"10.1111\/aji.12838","article-title":"Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria","volume":"79","author":"Monteiro","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1093\/humrep\/dey116","article-title":"Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment","volume":"33","author":"Alfano","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fmicb.2019.00234","article-title":"Sperm microbiota and its impact on semen parameters","volume":"10","author":"Baud","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.resmic.2015.03.009","article-title":"Complementary seminovaginal microbiome in couples","volume":"166","author":"Mandar","year":"2015","journal-title":"Res. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.anaerobe.2011.04.015","article-title":"Influence of sexual intercourse on genital tract microbiota in infertile couples","volume":"17","author":"Borovkova","year":"2011","journal-title":"Anaerobe"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0015-0282(00)01624-1","article-title":"Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization","volume":"74","author":"Moore","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1093\/oxfordjournals.humrep.a019470","article-title":"Incidence of microbial growth from the tip of the embryo transfer catheter after embryo transfer in relation to clinical pregnancy rate following in-vitro fertilization and embryo transfer","volume":"11","author":"Egbase","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/S0015-0282(98)00277-5","article-title":"Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome","volume":"70","author":"Fanchin","year":"1998","journal-title":"Fertil. Steril."},{"key":"ref_17","doi-asserted-by":"crossref","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":"ref_18","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jri.2013.03.004","article-title":"Sperm viral infection and male infertility: Focus on hbv, hcv, hiv, hpv, hsv, hcmv, and aav","volume":"100","author":"Garolla","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Marci, R., Gentili, V., Bortolotti, D., Lo Monte, G., Caselli, E., Bolzani, S., Rotola, A., Di Luca, D., and Rizzo, R. (2016). Presence of hhv-6a in endometrial epithelial cells from women with primary unexplained infertility. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158304"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Souho, T., Benlemlih, M., and Bennani, B. (2015). Human papillomavirus infection and fertility alteration: A systematic review. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126936"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Foresta, C., Patassini, C., Bertoldo, A., Menegazzo, M., Francavilla, F., Barzon, L., and Ferlin, A. (2011). Mechanism of human papillomavirus binding to human spermatozoa and fertilizing ability of infected spermatozoa. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015036"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/S0015-0282(97)81454-9","article-title":"The effect of human papillomavirus infection on sperm cell motility","volume":"67","author":"Lai","year":"1997","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/andr.284","article-title":"Hpv-DNA sperm infection and infertility: From a systematic literature review to a possible clinical management proposal","volume":"3","author":"Foresta","year":"2015","journal-title":"Andrology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000434749","article-title":"Human papillomavirus positivity in women undergoing intrauterine insemination has a negative effect on pregnancy rates","volume":"81","author":"Depuydt","year":"2016","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Campisciano, G., Gheit, T., De Seta, F., Cason, C., Zanotta, N., Delbue, S., Ricci, G., Ferrante, P., Tommasino, M., and Comar, M. (2019). Oncogenic virome benefits from the different vaginal microbiome-immune axes. Microorganisms, 7.","DOI":"10.3390\/microorganisms7100414"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1136\/jcp.55.8.587","article-title":"Human papillomavirus associated with oesophageal cancer","volume":"55","author":"Matsha","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Khan, S., Rai, M.A., Khanani, M.R., Khan, M.N., and Ali, S.H. (2006). Hiv-1 subtype a infection in a community of intravenous drug users in pakistan. BMC Infect. Dis., 6.","DOI":"10.1186\/1471-2334-6-164"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"Qiime allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using qiime 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fettweis, J.M., Serrano, M.G., Sheth, N.U., Mayer, C.M., Glascock, A.L., Brooks, J.P., Jefferson, K.K., and Buck, G.A. (2012). Species-level classification of the vaginal microbiome. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-S8-S17"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40168-017-0268-4","article-title":"A critical assessment of the \u201csterile womb\u201d and \u201cin utero colonization\u201d hypotheses: Implications for research on the pioneer infant microbiome","volume":"5","author":"Arrieta","year":"2017","journal-title":"Microbiome"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lyu, Z., Feng, X., Li, N., Zhao, W., Wei, L., Chen, Y., Yang, W., Ma, H., Yao, B., and Zhang, K. (2017). Human papillomavirus in semen and the risk for male infertility: A systematic review and meta-analysis. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2812-z"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40470","DOI":"10.1155\/IDOG\/2006\/40470","article-title":"Epidemiology and natural history of human papillomavirus infections in the female genital tract","volume":"2006","author":"Ault","year":"2006","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10815-007-9146-5","article-title":"Examination of bacterial contamination at the time of embryo transfer, and its impact on the ivf\/pregnancy outcome","volume":"24","author":"Selman","year":"2007","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1128\/JCM.00558-07","article-title":"Lactobacillus iners: A marker of changes in the vaginal flora?","volume":"45","author":"Jakobsson","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1128\/JCM.02085-06","article-title":"Cultivation-independent analysis of changes in bacterial vaginosis flora following metronidazole treatment","volume":"45","author":"Ferris","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jri.2013.07.004","article-title":"Tunel analysis of DNA fragmentation in mouse unfertilized oocytes: The effect of microorganisms within human follicular fluid collected during ivf cycles","volume":"99","author":"Pelzer","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pelzer, E.S., Allan, J.A., Waterhouse, M.A., Ross, T., Beagley, K.W., and Knox, C.L. (2013). Microorganisms within human follicular fluid: Effects on ivf. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059062"},{"key":"ref_40","first-page":"535","article-title":"Evaluation of the inhibitory effects of vaginal microorganisms on sperm motility in vitro","volume":"19","author":"Wang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-019-0562-z","article-title":"The complex microbiome from native semen to embryo culture environment in human in vitro fertilization procedure","volume":"18","author":"Stsepetova","year":"2020","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.fertnstert.2004.01.042","article-title":"Performance of the postwash total motile sperm count as a predictor of pregnancy at the time of intrauterine insemination: A meta-analysis","volume":"82","author":"Repping","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3109\/09513590.2014.984678","article-title":"Male factors in art outcome prediction","volume":"31","author":"Brincat","year":"2015","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.anaerobe.2008.08.002","article-title":"Prevotella bivia as a source of lipopolysaccharide in the vagina","volume":"14","author":"Aroutcheva","year":"2008","journal-title":"Anaerobe"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fpubh.2018.00078","article-title":"Vaginal microbiomes associated with aerobic vaginitis and bacterial vaginosis","volume":"6","author":"Kaambo","year":"2018","journal-title":"Front. 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