Endometrial receptivity: The omics revolution

Infertility, affecting millions globally, remains a significant challenge despite advances in Assisted Reproductive Technologies (ART) over the past four decades. While the success rates have improved, many couples still face challenges in conceiving. A major contributing factor is the limited understanding of infertility causes and the inefficiency of available treatment solutions. This article delves into the intricate processes of embryonic implantation and endometrial receptivity, crucial aspects of successful pregnancy. The emphasis is placed on the frequently overlooked endometrial environment in the context of In Vitro Fertilization (IVF) procedures. Traditional methods of assessing endometrial receptivity, such as histological examination and hormonal level monitoring, have proven insufficient. In the last years, omics approaches have generated a vast amount of highly valuable information, contributing significantly to the comprehension of the endometrial environment necessary for successful embryonic implantation. Genomic studies have unveiled specific loci related to endometrial disorders, epigenetic regulation studies have identified distinctive signatures associated with receptivity and endometrial pathologies, proteomic analysis has revealed protein expression changes during the menstrual cycle and metabolomic signatures in endometrial fluid may offer a direct insight into tissue function. Among these methodologies, transcriptomic analysis stands out as the most advanced. Particularly, high-throughput methods have proven to be robust in assessing functional states and pathologies leading to the development of commercial tests that evaluate endometrial receptivity. Recent advancements in single-cell and spatial transcriptomics provide great potential for the advanced study of endometrial function. Current and emerging technologies employed in the exploration of the uterine compartment exhibit significant promise for advancing diagnostic methodologies and therapies addressing infertility. Despite existing challenges, we believe that the key to optimizing ART success rates lies in advanced assessments of the endometrial environment. As technology continues to evolve, the possibilities of precision medicine and personalized approaches offer hope and new opportunities for couples pursuing parenthood.