Endometriosis is a potentially debilitating condition that affects a high percentage of women that are of reproductive age and can cause pain, irregular bleeding, infertility and recurrent miscarriage. Endometriosis occurs when endometrial tissue, which normally lines the inside of the uterus (eutopic endometrium), inappropriately establishes growths in other areas of the body (endometriotic lesions). Endometriotic lesions are typically established in the abdominal cavity and are thought to occur in part through retrograde menstruation, a process in which sloughed eutopic endometrium enters the abdominal cavity through the fallopian tubes.
Infertility and miscarriage related to endometriosis is multifactorial, involving impaired folliculogenesis, impaired ovulation, luteal defects and compromised oocyte quality. It is now also known that embryo implantation into the eutopic endometrium is impaired in women with endometriosis. A great deal of research on implantation failure related to endometriosis has revealed reduced endometrial receptivity due to aberrant expression of adhesion molecules, such as integrins, that are involved in binding to the embryo. Reduced expression of these adhesion molecules in endometriosis appears to be related to resistance of the eutopic endometrium to the effects of progesterone – a phenomenon known as "progesterone resistance".
Endometriosis is also characterized as an inflammatory disorder that involves elevated levels of inflammatory mediators (cytokines) and multiple changes in the function of immune system components including macrophages, NK cells, T cells and B cells. Newer research has now started to explore the potential contributions of these immune system changes to altered function of the eutopic endometrium. This research has identified, amongst other things, changes in the numbers and function of dendritic cells and regulatory T cells (Tregs) in the eutopic endometrium of endometriosis patients. Additionally, endometriosis is associated with activation of B cells and their production of autoantibodies that bind to molecules in eutopic endometrium (anti-endometrial antibodies). Several of these antibodies, including anti-laminin-1 antibodies, have been found to be associated with infertility and recurrent miscarriage in endometriosis patients.
At Braverman IVF & Reproductive Immunology, we are currently developing tests based on these alterations in eutopic endometrium and immune system function in endometriosis patients to help identify those patients at increased risk for infertility, implantation failure and recurrent miscarriage. These tests will detect specific cellular and molecular defects present in patients with endometriosis that will allow us to further personalize and tailor our treatment protocols for these patients.
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