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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1504609

This article is part of the Research TopicMaternal and Infant Microbiota during Gestation and the Postpartum PeriodView all articles

Main Differential Endometrial Microbiota Associated With Recurrent Implantation Failure: A case control study

Provisionally accepted
Hong  GaoHong Gao1,2*Jing  XiaoJing Xiao3Bingyan  LiangBingyan Liang3Xiaolan  WangXiaolan Wang4Huanhuan  LiHuanhuan Li1Genlin  LiGenlin Li4Baoyu  WuBaoyu Wu1*
  • 1Second Affiliated Hospital of University of South China, Hengyang, Hunan Province, China
  • 2Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada
  • 3School of Nursing, University of South China, Hengyang, Hunan Province, China
  • 4The First Affiliated Hospital, University of South China, Hengyang, Hunan Province, China

The final, formatted version of the article will be published soon.

To identify the main differential endometrial microbiota associated with recurrent implantation failure (RIF) and to establish threshold values for their relative abundance. This case-control study was conducted in the Departments of Obstetrics, Gynecology, and Reproductive Medicine at two large hospitals. From March to December 2023, the study recruited 17 infertile patients with RIF (Group A, cases), 19 healthy non-pregnant women (Group B, controls), and 20 healthy pregnant women (Group C, controls). Demographic information, medication history, clinical data, and endometrial tissue samples were collected. Endometrial microbiota of all participants was profiled using 16S rRNA gene sequencing. The richness of endometrial microbiota in Group A was significantly lower compared to both control groups (P=0.013, P=0.022, respectively). The diversity of endometrial microbiota in Group A and B was significantly higher compared to Group C (P=0.043, P=0.002, respectively). The composition of endometrial microbiota in Group A differed significantly from both control groups, whereas only minor differences were observed between the two control groups (PERMANOVA, P=0.001). Methyloversatilis, Lactobacillus, Sphingomonas, Faecalibacterium, Escherichia-Shigella, Bacteroides, and Aeromonas were identified as the main differential endometrial microbiota associated with RIF, with threshold relative abundances of 3.807%, 6.606%, 0.192%, 0.193% , 0.618%, 2.411%, and 0.019%, respectively. In Group A, Lactobacillus was positively correlated with Sphingomonas (r=0.64, P=0.005). Methyloversatilis, Lactobacillus, Sphingomonas, Faecalibacterium, Escherichia-Shigella, Bacteroides, and Aeromonas were the main differential endometrial microbes associated with RIF.Preliminary threshold values for their relative abundances were established.

Keywords: recurrent implantation failure, Endometrial microbiota, Endometrial tissue, major differential microorganisms, 16S ribosomal RNA gene sequencing

Received: 05 May 2025; Accepted: 23 Jul 2025.

Copyright: © 2025 Gao, Xiao, Liang, Wang, Li, Li and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hong Gao, Second Affiliated Hospital of University of South China, Hengyang, Hunan Province, China
Baoyu Wu, Second Affiliated Hospital of University of South China, Hengyang, Hunan Province, China

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