O-260 The influence of the vaginal microbiome on clinical outcomes in patients undergoing a frozen embryo transfer: a prospective pilot study
Authors: Povey C , Labarta Demur E , Rodríguez-Varela C , Savash M C , Wells D , Spath K 
Published: June 2023

Abstract

Study question
Are Lactobacillus-dominant vaginal microbial compositions advantageous for clinical outcomes and is the specific Lactobacillus species relevant?

Summary answer
Favourable clinical outcomes are increased in patients with a Lactobacillus-dominant vaginal microbiome, particularly in those patients with microbial communities dominated by L.crispatus and L.jensenii.

What is known already
The clinical relevance of the urogenital microbiome is emerging as a topic in female reproductive health. Recent evidence suggests that the composition of the vaginal microbiome may have an impact on clinical outcomes in patients undergoing assisted reproductive treatment. A Lactobacillus-dominant microbiome (LDM), typically composed of L.crispatus, L.gasseri, L.iners or L.jensenii, is considered to be associated with favourable outcomes. In contrast, a non-Lactobacillus-dominated microbiome (NLDM), consisting predominantly of anaerobe species, may be linked to poor outcomes. The evidence surrounding this relationship is controversial and the importance of relative Lactobacillus abundance in the vagina in relation to clinical outcomes remains unclear.

Study design, size, duration
A single-centre prospective pilot study included 81 patients (mean age: 38.2) undergoing frozen embryo transfer using their own (n = 52) or donated (n = 29) oocytes. A vaginal swab was taken on the embryo transfer day and the microbiome analysed. Implantation, ongoing pregnancy and early miscarriage rates were compared between different microbiome compositions. To minimise the confounding effect of aneuploidy on clinical outcomes, a patient sub-group (n = 54) receiving donor oocytes or a euploid embryo transfer was also considered.

Participants/materials, setting, methods
Quantitative PCR was utilised to determine the relative abundance of the four predominant Lactobacillus species as well as 15 species associated with vaginal dysbiosis. Microbiome compositions were grouped according to the relative Lactobacillus abundance and patients divided into an LDM (&gt;80%) or NLDM (&lt;80%) group. Patients were further sub-divided into community state types (CSTs) according to the dominant species present in their sample (CST-I: L.crispatus, CST-II: L.gasseri, CST-III: L.iners, CST-V: L.jensenii and CST-IV: dysbiotic species).

Main results and the role of chance
Relative abundance of Lactobacillus was significantly higher in samples from patients achieving an ongoing pregnancy (80.7% vs. 61.7%; p = 0.05). Implantation rates were comparable between LDM and NLDM patients (66.0% and 64.3%), but the ongoing pregnancy rate showed an apparent increase in LDM patients (58.5% vs. 39.3%; p = 0.11), concomitant with a significant decrease in the miscarriage rate (11.4% vs. 38.9%; p = 0.03). Limiting the analysis to patients at low risk of aneuploidy (young donor and PGT-A cycles), Lactobacillus abundance appeared higher in patients with ongoing pregnancies (74.8% vs. 58.0%; p = 0.34). Likewise, LDM patients showed higher ongoing pregnancy (61.3% vs. 43.5%; p = 0.27) and lower miscarriage (5.0% vs. 33.3%; p = 0.06) rates, although significance was not achieved in this restricted sample. Comparison of CST groups indicated better outcomes in CST-I and CST-V compared to other groups. The ongoing pregnancy rate was significantly higher (65.7% vs. 41.3%; p = 0.04), alongside a lower miscarriage rate (8.0% vs. 32.1%; p = 0.04). When only considering patients with low aneuploidy risk, similar results were obtained (implantation rate: 78.9% vs. 57.1%, p = 0.14; ongoing pregnancy rate: 73.7% vs. 42.9%, p = 0.04; miscarriage rate: 6.7% vs. 25.0%, p = 0.21). Of note, there were no differences in baseline characteristics (age, ethnicity & BMI) or embryo morphologies between groups.

Limitations, reasons for caution
All patients were from a single fertility clinic and the study population was predominantly composed of white women. Consequently, results may not be applicable to women of different ethnicities. Patients with a low risk of aneuploid embryo transfer represented a small subgroup where meaningful statistical analysis was not always possible.

Wider implications of the findings
This study identifies a correlation between Lactobacillus species colonisation in the vagina and successful clinical outcomes, suggesting that the vaginal microbiome modulates the chances of IVF success. The results are promising, providing motivation for further, larger studies, involving more diverse populations in order to draw definitive conclusions.

Trial registration number
not applicable