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Background: Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics., Methods: This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a Lactobacillus -dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an in vitro microbiome competition assay., Findings: A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1 s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of Gardnerella spp. After one VMT there was a complete shift in microbiome composition to 81.2% L. crispatus and 9% L. jensenii with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term., Interpretation: Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required., Funding: The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark., Competing Interests: Elleke F. Bosma, Brynjulf Mortensen, Kevin DeLong and Johan van Hylckama Vlieg are employees of Freya Biosciences. Johan van Hylckama Vlieg, Anne Bloch Thomsen and Laura Ensign are shareholders of Freya Biosciences. Elleke F. Bosma and Brynjulf Mortensen are listed as inventors on a patent application filed on the use of VMT for RPL. Laura Ensign is the Chair of the Scientific Advisory Board for Freya Biosciences, receives consulting payments from Freya Biosciences, and is an inventor on patent applications related to VMT that are owned by Johns Hopkins University. Anne Bloch Thomsen is a full-time employee of Pfizer as Country Medical Director, CMO of Pfizer Denmark and Iceland and is on the Board of Pfizer Denmark, and is a board member of EMPROS Pharma Sweden. Henriette Svarre Nielsen has received scientific grants from Freya Biosciences, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordisk Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, and Ole Kirks Fond. HSN received personal payment or honoraria for lectures and presentations from Ferring Pharmaceuticals, Merck, Astra Zeneca, Cook Medical, and IBSA Nordic. Henrik Westh, Andreas Munk Petersen Sarah Mollerup received materials for the study funded by Freya Biosciences and paid to institution. Tine Wrønding, Kilian Vomstein and Julie Elm Heinz do not have any conflicts of interest regarding this publication., (© 2023 The Author(s).)