Implantation defects in infertile women with endometriosis

The endometrium undergoes characteristic histologic changes during the menstrual cycle as it prepares for embryo implantation. Historic and current data suggest the presence of a defined period of maximal uterine receptivity during the mid-secretory phase occurring between days 7 and 10 post-ovulation. In recent years, we and others have sought to define biochemical markers of receptivity that might be used to better understand this time of endometrial differentiation. Based on the work with cell adhesion molecules, we have discovered three different integrins that are only coexpressed during this time in the cycle when embryos will successfully implant. By studying the regulation of one of these, the alphanubeta3 integrin, and its extracellular matrix ligand, osteopontin (OPN), we have defined two separate regulatory pathways that may regulate endometrial receptivity. While alphanubeta3 expression appears to be stimulated by EGF or heparin-binding EGF, osteopontin is stimulated by progesterone. We now believe the former pathway is a paracrine-mediated signal, while the latter is a direct effect of progesterone on the estrogen-primed endometrial epithelium. In women with endometriosis, it appears that alphanubeta3 expression is reduced, while OPN expression is unaffected. Interestingly, binding of OPN to the surface epithelium appears quite limited when alphanubeta3 expression is lacking. Such evidence continues to reinforce the notion that endometrium from some women with endometriosis is dysfunctional and may account for the reduction in cycle fecundity noted in this group of patients.