Effect of hCG on Receptivity of the Human Endometrium

Embryo implantation in humans is surprisingly inefficient and represents a major limiting factor for enhancement of ART success rates (ref 1-2). Successful implantation requires synchronized development between the newly fertilized embryo and the maternal endometrium within a specific window of time. In mammals, this coordinated development is accomplished, in part, by embryonic secretions which alert the body that fertilization has occurred. One of the earliest proteins produced by the embryo is human chorionic gonadotropin (hCG). Previous research has shown that hCG maintains progesterone production by the ovary, a hormone required for the maintenance of pregnancy. However, very little is known about the direct effect of hCG on the human endometrium. Our laboratory has previously shown that intrauterine infusion of hCG in the non-human primate can induce endometrial changes that mimic the initial stages of early pregnancy (i.e. altered cellular morphology, pre-decidual response and increased glandular activity; ref 3-4). These results suggest that embryo-derived hCG may also act directly upon the endometrium to "prime" it in anticipation of implantation. Research from other labs examining the effect of hCG on endometrial genes in vitro support this hypothesis (ref: 5-9). Additionally, a recent study of women undergoing ART revealed significantly increased implantation and pregnancy rates when the embryo transfer was preceded by intra-uterine infusion of 500IU hCG (ref 10). The purpose of this study is to determine whether the endometrial response to hCG seen previously in our non-human primate model is also present in women and to characterize this effect. Women who plan to undergo controlled ovarian stimulation for the purpose of egg donation will be eligible to participate in this research. Subjects in experimental group will receive a single intrauterine infusion of hCG (500IU) diluted in IVF media 3 days after oocyte retrieval. Control subjects will receive a single intrauterine infusion of IVF media only. Two days after infusion, both experimental group and control participants will return to the clinic where a sample of endometrial tissue will be obtained via pipelle biopsy and a sample of uterine secretory proteins will be obtained via uterine lavage. The uterine lavage samples will be examined using ELISA/proteomic analysis to determine the effect of hCG on uterine protein secretions. One portion of the endometrial biopsy will be formalin-fixed and paraffin-embedded for analysis of morphological and structural changes following hCG exposure. The second portion will be used for cellular and molecular analysis to determine the effect of hCG on genes and proteins of interest.