Endometrial microbiota composition is associated with reproductive outcome in infertile patients

Inmaculada Moreno,Michael Dimattina,Elena Puente,Mustafa Bahçeci,Felipe Vilella,Iolanda García-Grau ,Alejandro Chavez,M.p Leondires ,Mira Aubuchon,Georgina Meneghini,Diana Valbuena,David Pérez-Villaroya ,Ken Seethram,Marta Gonzáléz-Monfort ,M.w Lim ,Martina Perez-Olgiati,Carlos José Jaramillo Gómez ,Davide Baù ,Marcelo J Barrionuevo,Alexandra Izquierdo,Sagiri Taguchi,Carlos Simón

doi:10.1186/s40168-021-01184-w

Abstract

BackgroundPrevious evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy.MethodsHere, we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments.ResultsA dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes.ConclusionsOur findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies.4s24pSLHML6tsFwrrAE7giVideo .

Highlights

Humans have co-evolved as holobionts with microbial companions including bacteria, viruses, fungi, yeast and archaea [59]
Recent studies indicate that the chance of becoming pregnant before the start of an in vitro fertilisation (IVF) treatment is stratified based on the vaginal microbiota composition, as women with a low percentage of Lactobacillus in their vaginal sample are less likely to have a successful embryo implantation [32]
The endometrial microbiome (EM) during early successful pregnancy exhibited no bacterial diversity and higher Lactobacillus abundance [45]. In this prospective multicentre observational study, we investigated the EM composition in 342 infertile patients undergoing assisted reproductive technology (ART) in 13 different centres on 3 continents by analysing endometrial fluid (EF) and endometrial biopsy (EB) samples using 16S rRNA sequencing

Summary

Introduction

Humans have co-evolved as holobionts with microbial companions including bacteria, viruses, fungi, yeast and archaea [59]. Analyses by 16S ribosomal RNA (16S rRNA) gene sequencing of endometrial samples suggest that this microbiome impacts reproductive outcomes in infertile patients. 16S rRNA and whole metagenomics sequencing have been used to investigate the endometrial microbiome (EM) in cases of spontaneous clinical miscarriage [45], recurrent miscarriage [22] and at 4 weeks gestation in a pregnancy resulting in a live birth [45]. Previous evidence indicates associations between the female reproductive tract microbiome com‐ position and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy

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Conclusion