Development of a New Personalized Molecular Test Based on Endometrial Receptivity and Maternal-Fetal Dialogue: Adhesio.

Abstract

Successful embryo implantation relies on a receptive endometrium and a maternofetal dialogue. Abnormal receptivity is a common cause of implantation failure in assisted reproductive techniques. This study aimed to develop a novel transcriptomic-based diagnostic assay, Adhesio, for assessing endometrial receptivity and guiding personalized embryo transfer. Adhesio was developed based on an initial dataset of 74 endometrial biopsies. Two types of biopsy samples were involved: 45 endometrial biopsies collected during the optimal theoretical window of implantation (WOI) and 29 endometrial biopsies which cells have been cultured with or without an autologous embryo. Microarray analysis was performed to identify differentially expressed genes associated with endometrial receptivity and selected candidate genes were assessed using quantitative real-time polymerase chain reaction (RT-qPCR) on biopsy samples. Statistical analyses were conducted to assess the performance and accuracy of Adhesio. The microarray analysis identified three distinct clusters of endometrial samples with differential gene expression patterns. Cluster 1 exhibited 1717 differentially expressed genes involved in biological processes associated with endometrial receptivity. A specific transcriptomic signature of 60 genes associated with endometrial co-culture was obtained using class prediction approach. Thereafter, an original panel of 10 genes was selected as potential biomarkers for endometrial receptivity based on their expression profiles in both endometrial biopsies and co-cultured cells. This article outlines the methodology employed to develop Adhesio, a test that assesses endometrial receptivity using an original panel of 10 genes. These genes are not only involved during the WOI but are also influenced by the maternal-fetal dialogue.