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The maternal factor in the embryonic implantation process: the microbiome and endometrial receptivity

Carlos Simon

2019年度 年次大会-講演抄録 | 反復着床不全への対応

学会講師 : Carlos Simon

Abstract

The endometrium is a hormonally regulated organ that is non-adhesive to embryos throughout most of the menstrual cycle in humans. Endometrial receptivity refers to a hormone-limited period in which the endometrial tissue acquires a functional and transient ovarian steroid-dependent status allowing blastocyst adhesion. Functional genomic studies of human endometrium in natural cycles have demonstrated that endometrial receptivity is an active process involving up- and down-regulation of hundreds of genes.

Personalized medicine is a well-accepted concept in reproductive medicine except for the endometrial factor that is still neglected. Our group has developed the endometrial receptivity analysis (ERA), composed by the transcriptomic signature of 238 genes using Next Generation Sequencing(NGS) coupled to a computational predictor capable of diagnosing the window of endometrial receptivity regardless of its histological appearance.

The discovery of microbial communities inhabiting the whole female reproductive tract has challenged the traditional view of human fetal development in a sterile environment. Technical advances have facilitated the study of the bacterial microbiome in the upper and lower genital tract, as well as the role of such bacteria in women’s health and fertility. The microbiota in the urogenital tract of healthy reproductive age women is mainly composed of bacteria from the Lactobacillus genus; however, structural or compositional variations of this microbiota, that could occur throughout a women’s life in response to intrinsic and extrinsic factors may impact the function of reproductive organs.

In this presentation we will update the diagnostic and therapeutic efficiency of ERA in patients with implantation failure (IF), through personalization of the day of embryo transfer (pET) as well as the results of our international RCT to investigate the reproductive outcome of infertile women under 38 year (BMI of 18.5-30 and AFC > 8) s in their first IVF/ICSI cycle with elective blastocyst transfer randomly allocated to be performed in a fresh cycle, after freezing all embryos or after identification of the personalized WOI with the ERA test(pET).

reproductive outcome in terms of implantation, pregnancy and live birth rates.reproductive outcome in terms of implantation, pregnancy and live birth rates.
Finally, the investigation of endometrial bacterial communities has revealed that the endometrial cavity is not sterile. The presence of a Non-Lactobacillus- dominated microbiota(NLD)(<90% Lactobacilli)or pathogens responsible for chronic endometritis in infertile patients are associated with decrease reproductive outcome in terms of implantation, pregnancy and live birth rates.

This work was supported by the EU FP7- PEOPLE-2012-IAPP grant SARM, No. 324509.

The discovery of microbial communities inhabiting the whole female reproductive tract has challenged the traditional view of human fetal development in a sterile environment. Technical advances have facilitated the study of the bacterial microbiome in the upper and lower genital tract, as well as the role of such bacteria in women’s health and fertility. The microbiota in the urogenital tract of healthy reproductive age women is mainly composed of bacteria from the Lactobacillus genus; however, structural or compositional variations of this microbiota, that could occur throughout a women’s life in response to intrinsic and extrinsic factors may impact the function of reproductive organs. Non- lactobacilli dominant microbiome in the uterine cavity has been associated with poor reproductive IVF outcomes, by increasing implantation failure and miscarriage. For this reason, assessment of the endometrial microbiome has been proposed to be considered in infertile patients with implantation failure to improve our understanding and develop personalized strategies to improve clinical results. This presentation will focus on the current knowledge of the endometrial microbiome and their functional relevance in the reproductive process.

 

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