ALTERATIONS IN ENDOMETRIAL PROGRAMMING LEADS TO RECURRENT IN VITRO FERTILIZATION FAILURES

SOLEDAD GORI; LAURA FERNÁNDEZ; GUSTAVO MARTINEZ; ROSANNA RAMHORST; ELIZABETH SOCZEWSKI; ANA SCHAFIR; LUCILA GALLINO; LARA CASTAGNOLA; ESTEBAN GRASSO; MARCELA IRIGOYEN; CLAUDIA PÉREZ LEIRÓS

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC, SAIC, SAFIS

Embryo implantation efficiency in humans is very low because it requires a competent blastocyst during the endometrium’s window of implantation (WOI). Patients with repeated implantation failure (RIF) don’t reach implantation even if a competent blastocyst is transferred during WOI. Our hypothesis is that RIF patients present alterations on the decidualization program, affecting decidual cells’ functions, and on the associated inflammatory response. First, we performed bioinformatic analysis in endometrial biopsies from RIF patients vs fertile, based on standardized pathways in public data bases. We focused on genes that connected and were modulated in processes involved in implantation, angiogenesis, placentation, decidualization, inflammation and immune regulation. Then, we validated expression of 15 genes with highest score in biopsies from RIF or fertile women taken on LH+7 by RT-qPCR. We found decreased IGFBP1 expression, early decidualization marker, and the progesterone receptor (p<0,0001), suggesting alterations in the decidualization program. Since inflammation is associated with decidualization, we evaluated IL1b pathway. RIF biopsies had similar IL1b expression while NRLP3 was reduced (associated with inflammasome). So, we evaluated genes involved in processes regulated by inflammation. We observed increased MUC1, avoiding blastocyst adhesion, and decreased ITGA8 preventing its attachment (p<0,0028); accompanied by decreased MMP9 levels, inhibiting trophoblastic invasion.Finally, we isolated and cultivated stromal cells from RIF samples to analyze migration ability (process that mediates blastocyst inclusion into the decidua) by wound healing assay. These primary cultures showed a differential migration pattern compared with decidualized stromal cells (with MPA and cAMP). Our results demonstrate that  RIF patients display alterations in the decidualization program that might condition inflammation, attachment and migration preventing embryo implantation.