Preparing for human pregnancy: Models to investigate endometrial to embryo cross-talk

Abstract

Many couples experience infertility and require the intervention of Assisted Reproductive Technologies (ART). However, many of these couples experience consecutive loss of three or more embryos during single embryo transfer; a phenomenon which is clinically known as recurrent implantation failure (RIF). Many factors are associated with causing RIF, such as maternal endocrinological diseases, a deficiency in the maternal immune response, uterine anomalies, and endometrial malfunctions including the improper receptivity of the endometrial tissue and lag of the critical window of implantation (WOI). Embryonic factors also contribute to RIF, such as genetic aneuploidies of the developing blastocyst, and abnormalities pertaining to the embryonic protein profile and secretome; which may be investigated through the means of proteomics. Finally, the malfunctions of the exchange of endocrine, paracrine, and many other factors which act as communication or cellular ‘cross-talk’ between the endometrium and embryo that regulate and establish pregnancy would also cause RIF. This literature review focuses on describing the endometrium and its regulation and differentiation by the maternal hypothalamic-pituitary-ovarian axis in anticipation of pregnancy, as well as describing the endometrial-embryonic interface and the importance of this delicate dialogue in establishing and maintaining pregnancy. Finally, this review will discuss the in-vitro models of investigating this interface. Future studies targeted towards the improvement and refinement of these models is crucial in order to ensure the models mimic the in-vivo environment as accurately as possible, therefore increasing the understanding of this delicate interface and ultimately improving ART live birth rates.