Analysis of vaginal and endometrial microbiota communities in infertile women with a history of repeated implantation failure.

Takuhiko Ichiyama,Keiji Kuroda,Takashi Yamaguchi,Motoharu Ohno,Atsuo Itakura,Fumio Yamasaki,Yoshiyuki Sakuraba,Atsushi Tanaka,Daichi Urushiyama,Satoru Takeda,Yoko Nagai,Kenichiro Hata,Motoi Nagayoshi,Shingo Miyamoto

doi:10.1002/rmb2.12389

Abstract

PurposeTo identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next‐generation sequencing.MethodsWe investigated α‐ and β‐diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure.ResultsThe endometrial microbiotas had higher α‐diversities than did the vaginal microbiotas (P < .001). The microbiota profiles showed that vaginal and endometrial samples in RIF patients had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in controls. Vaginal Lactobacillus rates in RIF patients were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (P = .018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, P = .79).ConclusionsImpaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The vaginal Lactobacillus rates, but not the endometrial, may be a biomarker for RIF.

Highlights

Repeated implantation failure (RIF) is estimated to occur in 15%–20% of infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET)
Another clinical study using endometrial microbiota (EM) analysis in infertile patients demonstrated that endometrial Lactobacillus ratios did not affect pregnancy outcomes after In vitro fertilization (IVF) [13, 14]; evidence remains insufficient
We focused on infertile patients with RIF histories, evaluated their vaginal and EM communities via nextgeneration sequencing, and analyzed specific RIF-associated bacteria

Summary

Introduction

Repeated implantation failure (RIF) is estimated to occur in 15%–20% of infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). Twenty-one healthy women were enrolled as controls We investigated their vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared the microbiota profiles in the patients with RIF and controls. No study has confirmed the reproducibility of the effect of EM profiling on pregnancy outcomes after IVF. Another clinical study using EM analysis in infertile patients demonstrated that endometrial Lactobacillus ratios did not affect pregnancy outcomes after IVF [13, 14]; evidence remains insufficient

Methods

Results

Discussion

Conclusion