Effect of clindamycin and a live biotherapeutic containing lactobacilli on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: a double-blind, placebo-controlled multicentre trial

Abstract Study question Does treatment of abnormal vaginal microbiota improve the reproductive outcomes of IVF patients? Summary answer Data is being analysed and will be presented at ESHRE 2023. What is known already An increasing number of studies reported an association between abnormal genital tract microbiota and adverse reproductive outcomes in IVF patients. One hypothesis could be that vaginal microbiota ascend to the endometrium where the microbiota hampers implantation. To the best of our knowledge, this is the first study powered to investigate causality between abnormal genital tract microbiota - in this study defined by a bacterial vaginosis like vaginal microbiota - and clinical pregnancy rate in IVF patients. Study design, size, duration Double-blind, placebo-controlled multicentre trial in IVF patients diagnosed with abnormal vaginal microbiota and subsequently randomised into three parallel groups 1:1:1. The first group received clindamycin 300 mg ×2 daily for 7 days followed by vaginal Lactobacillus crispatus until the clinical pregnancy scan. The second group received clindamycin and placebo, whereas the third group received placebo/placebo. A total of 1518 patients were screened, and 338 patients were randomised. The study duration was from 2017 to 2023. Participants/materials, setting, methods IVF patients with any cause of infertility embarking on their first, second or third IVF stimulation cycle or embryo transfer were approached for inclusion. At a minimum 12 days prior to embryo transfer, patients were screened for abnormal vaginal microbiota defined by a qPCR assay, targeting high quantitative loads of Fannyhessea vaginae and Gardnerella spp. Patients were excluded if they had intrauterine malformations like polyps, septum, and fibroma. Main results and the role of chance Data and safety monitoring board has decided not to open the randomization code yet. The final dataset is being completed. Data is being analysed and will be presented at ESHRE 2023. Limitations, reasons for caution Data is being analysed and will be presented at ESHRE 2023. Wider implications of the findings The present drug intervention study used clindamycin and a live biotherapeutic containing Lactobacillus crispatus. The results of the study could have a worldwide important clinical impact on daily IVF practice as currently there is no evidence that screening and treating IVF patients with abnormal vaginal microbiota improves the reproductive outcome. Trial registration number EudraCT 2016-002385-31