Uterine Receptivity and Cytokines: New Concepts and New Applications

Abstract

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.

PreImplantation Factor (PIF) promoting role in embryo implantation: increases endometrial Integrin-α2β3, amphiregulin and epiregulin while reducing betacellulin expression via MAPK in decidua

“…Whether such leads to pro-inflammatory ligands secretion creating a favorable uterine milieu was examined. sPIF markedly increases several critical pro-inflammatory genes expression which in the innate arm of immunity, is involved in monocytes recruitment and in adaptive immunity in leukocyte recruitment and adhesion [9]. Endometrial-biopsy performed in IVF patients also increased local macrophage presence, GRO-α and other inflammatory mediators and led to improved pregnancy outcome [35].…”

Predictive value of bovine follicular components as markers of oocyte developmental potential

“…Both of these studies suggest that metabolomic analysis of follicular fluid may be a useful tool for characterising oocyte quality. Most recent data from human ART research points at the use of a panel of parameters to predict subsequent oocyte developmental potential (Lédée et al 2007). However, it is often difficult to obtain 'clean' data from human ART research as the numbers of tissues analysed in one clinic are often insufficient to generate statistically robust data and therefore datasets may be compiled from more than one clinic using different protocols.…”

In vitro Fertilization Outcome following Embryo Transfer with or without Preinstillation of Human Chorionic Gonadotropin into the Uterine Cavity: A Randomized Controlled Trial

“…Inappropriate implantation is the major cause in two thirds of in vitro fertilization (IVF) cycle failures [3,4,5]. Two main factors are believed to play a critical role in the implantation process - embryo quality and endometrial receptivity [6,7,8]. Since the introduction of assisted reproductive technologies (ART), several strategies have been developed to increase the implantation rate by improving endometrial and embryo qualities, transferring multiple embryos or treating comorbidities [6].…”