P-486 Alterations in endometrial programming lead to recurrent in vitro fertilization failures

Abstract Study question Could patients with recurrent implantation failures (RIF) display alterations on the decidualization program conditioning decidual cells’ functions and the inflammatory response during peri-implantation period? Summary answer Endometrium from RIF-patients displays alterations into the decidualization program and into the induction of a physiological inflammation preventing the attachment and cell-migration for embryo implantation What is known already The decidualization program starts on each menstrual cycle and implies not only phenotypical changes on the endometrial stromal cells, but also in their secretory profile. Moreover, this process induces a physiological and sterile inflammatory response associated with inflammatory mediators production, such as IL-1β. At the same time, several molecules associated with receptivity are modulated; increasing the expression of adhesion molecules and metalloproteinases, while decreasing MUC-1 to allow embryo attachment and implantation. Even nowadays with different techniques that can identify a competent embryo and the implantation window, RIF-patients cannot reach implantation and the mechanisms involved have not been elucidated yet. Study design, size, duration First, a bioinformatic analysis was performed using standardized pathways involved in angiogenesis, placentation, decidualization, inflammation and immune regulation from public databases (Reactome, Gene Ontology Biological Process, WikiPathways, KEGG). Based on arrays that compare gene expression in endometrial biopsies from RIF or fertile women, we selected those that connect two or more processes and we validated their modulation in endometrial samples. Functional processes, such as migration and inflammatory production were also evaluated in primary cultures. Participants/materials, setting, methods Endometrial samples were obtained from fertile and RIF patients during the secretory phase. The Investigation and Ethics Committee from San Isidro, Argentina approved this study. RT-qPCR was performed to test decidualization markers: IGFBP1, PRL, PGR; inflammation: IL-1β, NLRP3, PTGS1; angiogenesis balance : CXCL14, ARG2, VEGFA; adhesion molecules: ITGA8 and MUC1. IL-1β production was quantified by Flow Cytometry. Wound healing assay was performed in human endometrial stromal cells derived from cell line and RIF patient’s biopsy Main results and the role of chance First, we performed bioinformatic analysis based on standardized pat