Endometriosis is an estrogen-dependent inflammatory condition effecting women in their reproductive years. Endometriosis is attributed to cost in excess of $22 billion dollars in the US alone.  It is associated with pelvic pain and infertility and leads to implantation failure. While evidence points to an inflammatory immune response (Th1) being required for implantation, we find that sustained inflammation beyond the window of implantation likely interferes with establishment of pregnancy. Inflammatory cytokines are elevated in the peripheral circulation, peritoneal fluid and endometrial lavage of women with this disorder and may be associated with altered intrauterine leukocyte development and endometrial cell responses. These observations are relevant to both unexplained infertility as well as unexplained pregnancy loss.  A complete resection of endometriosis, both visible and invisible extensions, leads to healing and resolution of peripheral inflammatory changes, with improvement in pregnancy outcomes. Biomarkers of endometrial receptivity have provided insights into the underlying association between endometriosis and the mechanisms leading to infertility or pregnancy loss, including the regulation and dysregulation of leukemia inhibitor factor and alpha v/beta 3 integrin. The balance between progesterone and estrogen actions and the inflammatory milieu in humans will be the primary topic of this presentation.