Characterization of Microbiota in Endometrial Fluid and Vaginal Secretions in Infertile Women with Repeated Implantation Failure.

Kotaro Kitaya,Yoko Nagai,Yoshiyuki Sakuraba,Wataru Arai,Tomomoto Ishikawa

doi:10.1155/2019/4893437

Abstract

Studies suggest that persisting intrauterine bacterial infectious conditions such as chronic endometritis potentially impair the embryo implantation process. The microbial environment in the female reproductive tract, however, remains largely undetermined in infertile patients with a history of repeated implantation failure (RIF). Using next-generation sequencing, we aimed to characterize the microbiota in the endometrial fluid (EF) and vaginal secretions (VS) in women with RIF. Twenty-eight infertile women with a history of RIF and eighteen infertile women undergoing the first in vitro fertilization-embryo transfer attempt (the control group) were enrolled in the study. On days 6-8 in the luteal phase of the natural, oocyte-pickup, or hormone replacement cycle, the paired EF and VS samples were obtained separately. Extracted genomic DNA was pyrosequenced for the V4 region of 16S ribosomal RNA using a next-generation sequencer. The EF microbiota had higher α-diversity and broader bacterial species than the VS microbiota both in the RIF and control groups. The analysis of the UniFrac distance matrices between EF and VS also revealed significantly different clustering. Additionally, the EF microbiota, but not the VS microbiota, showed significant variation in community composition between the RIF group and the control group. Burkholderia species were not detected in the EF microbiota of any samples in the control group but were detectable in a quarter of the RIF group. To our best knowledge, this is the first study investigating the microbiota in the paired EF and VS samples in infertile women with RIF.

Highlights

The Human Microbiome Project revealed that bacterial cells account for ~3% of total human body weight and are at an equal level in number to human somatic cells
The prevalence of CE was higher in the repeated implantation failure (RIF) group than in the control group but did not reach a significant level (p = 0 38, relative risk 1.93, 95% CI 0.43 to 8.53)
This is the first study investigating the microbiota in the paired endometrial fluid (EF) and vaginal secretions (VS) samples in infertile patients with a history of RIF

Summary

Introduction

The Human Microbiome Project revealed that bacterial cells account for ~3% of total human body weight and are at an equal level in number to human somatic cells. While the bacterial communities in the human body contribute to health, their imbalance predisposes to a wide variety of diseases [1]. Lactobacillus species are classically known to dominate the vaginal cavity in premenopausal women [2]. The human uterine cavity has been long believed to be germfree. Recent studies proved the presence of a microbiota in the uterine cavity, which is characterized by Lactobacillus-dominant composition [3,4,5]. It was demonstrated that the status of the Lactobacillus-dominant (90% or more) microbiota in the endometrial fluid (EF) was favorable for embryo implantation in the subsequent in vitro fertilization-embryo transfer (IVF-ET) treatment in infertile women. Non-Lactobacillus-dominant microbiota is associated with a poor reproductive outcome including implantation failure and miscarriage [6], supporting the idea that

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