{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:44Z","timestamp":1785437924618,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016971","name":"Lomonosov Moscow State University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100016971","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/010pmpe69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: There is growing evidence that uterine microbiota might be linked to endometrial receptivity (ER) and affect the outcome of assisted reproductive technology (ART) procedures. Owing to the invasive nature of endometrial sampling, the evaluation of microbiota in this biomaterial is only possible outside the embryo transfer (ET) cycle. However, menstrual blood might be the key to overcoming this challenge as it can be safely aspirated from the uterine cavity at the beginning of the target ET cycle. This study aimed to evaluate the association of the microbiological profiles of menstrual blood with ER in patients undergoing frozen ET. Methods: Menstrual blood was obtained from 98 individuals scheduled for frozen ET in a private ART clinic (ET success rate\u201350%). DNA was isolated from menstrual sediment and analyzed using a multiplex quantitative PCR assay designed to identify 28 relevant microbial taxa and 3 Herpesviridae viruses. Results: Bacterial DNA was detected in 75.5% of samples. There were no associations between the abundance of individual microbial taxa and the outcome of ET, and the same was true for Shannon\u2019s \u03b1-diversity indices (p &gt; 0.05). However, Candida spp. and Enterobacteriaceae were detected exclusively in patients with negative ET outcomes (p = 0.028). Individuals with recurrent implantation failure had a significantly lower abundance of Lactobacillus spp. than the rest (0.0 [0.0; 7.4] vs. 2.8 [0.0; 91.9] %, p = 0.024). Conclusions: Menstrual blood aspirated directly from the uterus is a promising biomaterial for endometrial microbiological profiling. Upon further investigation, its analysis might become a useful tool in managing infertile patients scheduled for ART treatment.<\/jats:p>","DOI":"10.3390\/diagnostics16091403","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T08:01:39Z","timestamp":1778140899000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiological Profiling of Menstrual Blood Aspirated from the Uterus in Patients Undergoing Frozen Embryo Transfer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-8113","authenticated-orcid":false,"given":"Mark","family":"Jain","sequence":"first","affiliation":[{"name":"University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6103-3100","authenticated-orcid":false,"given":"Elena","family":"Mladova","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine \u201cREMEDI\u201d, 123100 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9602-4671","authenticated-orcid":false,"given":"Pavel","family":"Zalepaev","sequence":"additional","affiliation":[{"name":"University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7152-5976","authenticated-orcid":false,"given":"Margarita","family":"Gundobina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7536-1494","authenticated-orcid":false,"given":"Alexander","family":"Klimov","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-4777","authenticated-orcid":false,"given":"Liya","family":"Shcherbakova","sequence":"additional","affiliation":[{"name":"University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Samokhodskaya","sequence":"additional","affiliation":[{"name":"University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Panina","sequence":"additional","affiliation":[{"name":"University Clinic, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev-genom-090711-163814","article-title":"The Human Microbiome: Our Second Genome","volume":"13","author":"Grice","year":"2012","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in Health and Diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41522-025-00839-y","article-title":"Microbial Regulators of Physiological and Reproductive Health in Women of Reproductive Age: Their Local, Proximal and Distal Regulatory Roles","volume":"11","author":"Cheng","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1038\/s41380-023-02287-6","article-title":"Emerging Role of the Host Microbiome in Neuropsychiatric Disorders: Overview and Future Directions","volume":"28","author":"Hashimoto","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s42255-025-01287-w","article-title":"The Gut Microbiome and Cancer: From Tumorigenesis to Therapy","volume":"7","author":"Nobels","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.2021.4788","article-title":"Diagnosis and Management of Infertility: A Review","volume":"326","author":"Carson","year":"2021","journal-title":"JAMA"},{"key":"ref_8","first-page":"1443","article-title":"Infertility Affects 1 in 6 People Globally","volume":"329","author":"Harris","year":"2023","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and Infertility: Definition and Epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.fertnstert.2019.02.009","article-title":"What Exactly Is Endometrial Receptivity?","volume":"111","author":"Lessey","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_11","unstructured":"Tissier, H. (1900). Recherches Sur La Flore Intestinale Des Nourrissons:(\u00c9tat Normal et Pathologique), G. Carr\u00e9 et C. Naud."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0015-0282(16)33070-9","article-title":"Value of Endometrial Cultures in Sterility Investigation","volume":"9","author":"Butler","year":"1958","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stoyancheva, G., Mihaylova, N., Gerginova, M., and Krumova, E. (2025). Endometrial Microbiome and Reproductive Receptivity: Diverse Perspectives. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110796"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Olomu, I.N., Pena-Cortes, L.C., Long, R.A., Vyas, A., Krichevskiy, O., Luellwitz, R., Singh, P., and Mulks, M.H. (2020). Elimination of \u201cKitome\u201d and \u201cSplashome\u201d Contamination Results in Lack of Detection of a Unique Placental Microbiome. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01839-y"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jain, M., Mladova, E., Shichanina, A., Kirillova, K., Povarova, A., Scherbakova, L., Samokhodskaya, L., and Panina, O. (2023). Microbiological and Cytokine Profiling of Menstrual Blood for the Assessment of Endometrial Receptivity: A Pilot Study. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051284"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41392-024-01946-6","article-title":"A Systematic Framework for Understanding the Microbiome in Human Health and Disease: From Basic Principles to Clinical Translation","volume":"9","author":"Ma","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.fertnstert.2021.01.042","article-title":"Which Protocol for Frozen-Thawed Embryo Transfer Is Associated with the Best Outcomes for the Mother and Baby?","volume":"115","author":"Conrad","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177726","DOI":"10.1016\/j.ejphar.2025.177726","article-title":"Menstrual Blood and Endometrial Mesenchymal Stem\/Stromal Cells: A Frontier in Regenerative Medicine and Cancer Therapy","volume":"1000","author":"Rahnama","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/aogs.13990","article-title":"The Cytokine Profile of Menstrual Blood","volume":"100","author":"Strunz","year":"2021","journal-title":"Acta Obs. Gynecol. Scand."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2147\/MDER.S468500","article-title":"Innovative Hematology Analysis Using Menstrual Blood","volume":"17","author":"Wulandari","year":"2024","journal-title":"Med. Devices Evid. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Baker, J.M., Chase, D.M., and Herbst-Kralovetz, M.M. (2018). Uterine Microbiota: Residents, Tourists, or Invaders?. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00208"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9905","DOI":"10.1038\/s41598-019-46173-0","article-title":"Does the Endometrial Cavity Have a Molecular Microbial Signature?","volume":"9","author":"Winters","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/19396368.2023.2195040","article-title":"Comparison of Microbial Profiles and Viral Status along the Vagina-Cervix-Endometrium Continuum of Infertile Patients","volume":"69","author":"Jain","year":"2023","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_25","first-page":"e78982","article-title":"The Role of Endometrial Microbiota in Fertility and Reproductive Health: A Narrative Review","volume":"17","author":"Karadbhajne","year":"2025","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","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":"ref_27","doi-asserted-by":"crossref","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. Obs. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10815-015-0614-z","article-title":"Endometrial Microbiome at the Time of Embryo Transfer: Next-Generation Sequencing of the 16S Ribosomal Subunit","volume":"33","author":"Franasiak","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.1038\/s41598-023-30591-2","article-title":"The Endometrial Microbiota of Women with or without a Live Birth within 12 Months after a First Failed IVF\/ICSI Cycle","volume":"13","author":"Bui","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/rmb2.12389","article-title":"Analysis of Vaginal and Endometrial Microbiota Communities in Infertile Women with a History of Repeated Implantation Failure","volume":"20","author":"Ichiyama","year":"2021","journal-title":"Reprod. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Diaz-Mart\u00ednez, M.D.C., Bernabeu, A., Lled\u00f3, B., Carratal\u00e1-Munuera, C., Quesada, J.A., Lozano, F.M., Ruiz, V., Morales, R., Ll\u00e1cer, J., and Ten, J. (2021). Impact of the Vaginal and Endometrial Microbiome Pattern on Assisted Reproduction Outcomes. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184063"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cariati, F., Carotenuto, C., Bagnulo, F., Pacella, D., Marrone, V., Paolillo, R., Catania, M.R., Di Girolamo, R., Conforti, A., and Strina, I. (2023). Endometrial Microbiota Profile in In-Vitro Fertilization (IVF) Patients by Culturomics-Based Analysis. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1204729"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ma, J., Gao, W., and Li, D. (2023). Recurrent Implantation Failure: A Comprehensive Summary from Etiology to Treatment. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1061766"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"deac105-068","DOI":"10.1093\/humrep\/deac105.068","article-title":"P-384\u2003Efficacy of Endometrial Microbiome Metagenomic Analysis with Recurrent Implantation Failure and Recurrent Pregnancy Loss: Multicenter Study in Japan","volume":"37","author":"Iwami","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70005","DOI":"10.1111\/aji.70005","article-title":"Altered Endometrial Microbiota Profile Is Associated With Poor Endometrial Receptivity of Repeated Implantation Failure","volume":"92","author":"Zhang","year":"2024","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lozano, F.M., Lled\u00f3, B., Morales, R., Cascales, A., Hortal, M., Bernabeu, A., and Bernabeu, R. (2023). Characterization of the Endometrial Microbiome in Patients with Recurrent Implantation Failure. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030741"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e01324-22","DOI":"10.1128\/spectrum.01324-22","article-title":"Mycobiome Dysbiosis in Women with Intrauterine Adhesions","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.21037\/atm-20-2813","article-title":"Analysis of Endometrial Microbiota in Intrauterine Adhesion by High-Throughput Sequencing","volume":"9","author":"Qiu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hooker, A.B., de Leeuw, R.A., Emanuel, M.H., Mijatovic, V., Brolmann, H.A.M., and Huirne, J.A.F. (2022). The Link between Intrauterine Adhesions and Impaired Reproductive Performance: A Systematic Review of the Literature. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-05164-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.1038\/s41598-020-64739-1","article-title":"Clinical utility and cost-effectiveness of bacterial 16S rRNA and targeted PCR based diagnostic testing in a UK microbiology laboratory network","volume":"10","author":"Aggarwal","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e70067","DOI":"10.1111\/apm.70067","article-title":"Next Generation Sequencing Improves Diagnostic 16S rRNA Amplicon-Based Microbiota Analyses of Clinical Samples Compared to Sanger Sequencing","volume":"133","author":"Aftab","year":"2025","journal-title":"APMIS"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3201\/eid3113.241101","article-title":"16S Ribosomal RNA Gene PCR and Sequencing for Pediatric Infection Diagnosis, United States, 2020\u20132023","volume":"31","author":"Li","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/uog.24806","article-title":"Greater estimated fetal weight and birth weight in IVF\/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: Prospective cohort study with novel unified modeling methodology","volume":"60","author":"Cavoretto","year":"2022","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.fertnstert.2020.11.035","article-title":"Greater fetal crown-rump length growth with the use of in vitro fertilization or intracytoplasmic sperm injection conceptions after thawed versus fresh blastocyst transfers: Secondary analysis of a prospective cohort study","volume":"116","author":"Cavoretto","year":"2022","journal-title":"Fertil. Steril."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/9\/1403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:36:55Z","timestamp":1778215015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/9\/1403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["diagnostics16091403"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16091403","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}