Some reproductive failure are immunologically determined.
Overview about Endo-Immune Test
To analyses the immune competency of the endometrium, “Endo- Immune test” comprised of immune cells and cytokines described as active participants (uNK cells, Plasma Cells, Th1, Th17) in immunity-derived infertility. For implantation to occur, there must be a balance between pro-inflammatory and anti-inflammatory cytokines. The endometrium with Immune dysfunction is not ready for embryo attachment. The rejection of embryo occurs in such an environment. In women with recurrent pregnancy losses (RPL) (multiple miscarriages), recurrent implantation failure (RIF) and unexplained infertility, the immune balance is disturbed and leads to implantation failure. “Endo-Immune Test” finds out whether the immune imbalance in the endometrium is there or not, which hinders the implantation process. “Endo-Immune test” allows the identiﬁcation of implantation failure or recurrent miscarriage causes in the case where embryonic factors have been previously ruled out / normal.
Pregnancy is a complex immunological process for the mother. The maternal immune system plays a critical role in establishing, maintaining, and completing a healthy pregnancy. Cells and molecules of the maternal immune system interact in such a way as to prevent the rejection of the semiallogenic fetus and support its growth and development. Successful pregnancy is associated with a balance between Th1 & Th2-type immunity and Th17 & Treg cells. Th1-type immunity and Th17 responses are considered potentially dangerous and detrimental for continuing pregnancy. The increased number of uterine natural killer (uNK) cells, imbalance of Th1, Th17 cytokines, and the presence of plasma cells have been linked to habitual spontaneous abortion, RPL, and implantation failure. An Immune compromised endometrium cannot carry potential implantation and pregnancy to the term. The endometrium is the maternal tissue that comes into direct contact with the immunogenic embryo, so it is expected that an immune dysregulation of the endometrium may cause reproductive failure. A well-balanced equilibrium of the innate and adaptive local immune system is fundamental for successful implantation and pregnancy. To analyses the immune competency of the endometrium, we designed an "Endo- Immune test" comprised of immune cells and cytokines described as active participants (uNK cells, Plasma Cells, Th1, Th17) in immunity- derived infertility. "Endo- Immune test" allows the identification of implantation failure or recurrent miscarriage causes in the case where embryonic factors have been previously ruled out / normal.
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Uterine Natural killer (uNK) cells detect small cancerous cells and kill them before becoming tumors. If these cells are highly active, they may misinterpret the fetus as cancer and kill it. On the other hand, low activity of NK cells will lead to anomalies like infection and reduced angiogenesis. Hence, a moderate activity of NK cells is necessary to generate the balance required for successful implantation. The uNK cells, through the secretion of cytokines, also have extended mother self-tolerance to the fetus to avoid rejection. Th1 pro-inflammatory cytokines affect trophoblast cell growth and function directly, or they may cause activation of macrophages which could attack the trophoblast. TNF-α is a Th1pro-inflammatory cytokine, if produced excessively, can cause pathological changes and lead to tissue damage and chronic inflammation through necrosis or apoptosis. Further, pregnancy destroying molecules (PDMs) or IL-17 (a Th17 pro-inflammatory cytokine) are involved in the pathogenesis of inflammation, autoimmune diseases, and immunological rejection of non-self-tissue. An elevation in PDM results in the loss of self-tolerance of the fetus via its detrimental effect on the quality and quantity of T regulatory cells resulting in fetal rejection. Therefore, an imbalance between Th1:Th2 and Th17: Treg cells might lead to failure in implantation and other pregnancy problems. Chronic endometritis (CE) or chronic inflammation of the endometrial lining induces high uterine innate and adaptive immune cells at the fetal-maternal interface. Dysregulation of the uterine immune status due to CE may affect maternofetal tolerance, alter the endometrial receptivity, and lead to recurrent reproductive failure. CE is characterized by the infection-induced inflammation of the endometrium. Irregular bleeding, pelvic pain, or dyspareunia can be symptoms of CE; however, in most cases, patients with a CE remain asymptomatic. Chronic endometritis factor (CEF) or plasma cells are thought to cause CE that may lead to RIF, RM, and RPL. The reported prevalence of CE is 7%–56% in patients with RM, 10%–27% in RPL, and 7.7%–44% in RIF patients.
Several local and systemic modifications have been suggested to protect the developing fetus from maternal immune system attack. The available immune therapies and antibiotic treatments can help to improve reproductive outcomes, increasing the chance of embryo implantation. The Endo-immune test-guided patient-specific treatment will enhance the chances of implantation more effectively.