Characterization of vaginal microbiota during IVF fresh embryo transfer (IVF-ET) and in early pregnancy

Abstract Study question Does the composition of vaginal microbiota affect the success of IVF-ET? Does vaginal microbiota profile change intra-individually from IVF-ET to early pregnancy? Summary answer L. crispatus is associated with successful IVF outcome. The individual composition of vaginal microbiota tends to shift towards Lactobacillus-dominance between IVF-ET and early pregnancy. What is known already Lactobacilli are the most abundant species in healthy female reproductive tract microbiota and especially Lactobacillus crispatus is associated with good gynecological health. The composition of vaginal microbiota may also play an important role in infertility and the success of IVF. Women with Lactobacillus-dominated vaginal microbiota may have higher pregnancy rates after IVF-ET compared to women with non-Lactobacillus dominance, but the results have been controversial. In healthy pregnancy, vaginal microbiota is usually lactobacilli-dominated, whereas miscarriages are associated to a non-lactobacillus dominance. The intra-individual shift on the vaginal microbiota from ET to early pregnancy has not been studied earlier. Study design, size, duration This observational and longitudinal study investigates the effect of vaginal microbiota on the success of fresh IVF-ET. Another aim was to study the intra-individual changes in the microbiota profile between IVF-ET and early pregnancy. We recruited 76 subfertile women undergoing IVF with their own gametes between November 2019 and September 2021 in the Reproductive Medicine Unit, Helsinki University Hospital and in Oulu University Hospital. Main outcomes were clinical pregnancy and live birth. Participants/materials, setting, methods Study population composed of 76 subfertile women under 40 years of age. One IVF cycle including fresh embryo transfer was studied. Vaginal swabs were taken at the time of IVF-ET and at 8th gestational week. Samples were frozen in − 20 °C and moved to − 80 °C within four weeks. Microbiota analysis was performed with next-generation sequencing of 16S rRNA gene using Illumina MiSeq technology. Clinical data were collected from the patient registries and background questionnaires. Main results and the role of chance Altogether 30 (39.5%) of the 76 women achieved pregnancy after IVF-ET and 26 (34.2%) had live birth. The relative abundance of L. crispatus among women who achieved clinical pregnancy (46.9% vs. 19.1%, q = 0.003) and live birth (43.3% vs. 19.1%, q = 0.006) was significantly higher compared to women who did not. After adjusting for age, parity and gravidity, the results remained similar when comparing clinical pregnancy (q = 0.039), but in live birth, the difference lost significance (q = 0.14) Vaginal samples were taken at the 8th gestational week from 21 of 30 women who got pregnant. All samples were dominated by Lactobacillus species, mainly by L. crispatus (n = 16, 76.2%). Only two (9.2%) women had L. iners dominated microbiota at the early pregnancy. When comparing samples taken during fresh IVF-ET and early pregnancy, L. crispatus had significantly higher relative abundance in early pregnancy samples compared to the samples taken at the ET (71.5% vs. 43.4%, q = 0.001), whereas the relative abundance of L. iners (10.1% vs. 24.1%, q = 0.004), and G. vaginalis (0.8% vs. 14.7%, q = 0.004) decreased. Altogether 13 women had an intra-individual shift in their microbiota profiles. Limitations, reasons for caution The small sample size was the main limitation of our study. Larger studies are needed to confirm our findings and their relationship with the success of IVF-ET. Wider implications of the findings Vaginal microbiota at the time of fresh IVF-ET has an impact of the success of IVF treatment. Also, the intra-individual composition of vaginal microbiota between IVF-ET and early pregnancy changes in some women. The vaginal microbiota modification through probiotics in order to optimize the result of IVF warrants more studies. Trial registration number Not applicable