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Background of the study: The etiology of recurrent miscarriage (RM, defined as three or more consecutive miscarriages without any proven maternal or fetal cause), remains undiagnosed in more than 50% of cases. In these cases it is generally considered that a disturbance in the normal mother-embryo interactions is a causal factor. This disturbance may be based on a dysregulation of embryo invasiveness and/or decidual acceptance (e.g. altered decidualization; endometrial changes in preparation for the acceptance of a putative pregnancy). Moreover, dysfunctional maternal immune regulatory natural killer (NK) cells, implicated in tolerance induction and trophoblast invasion,may also underlie the occurrence of RM. The Selection Failure hypothesis for RM suggests that super-receptive endometrium (possibly due to increased embryo invasiveness and/or decidual acceptance and/or dysregulated immune cell function) may allow 'poor quality' embryos to implant and present as a clinical pregnancy before miscarrying. Fundamental knowledge on mechanisms of embryo implantation, decidual function and maternal immune reactivity in successful pregnancies has accumulated over the past 5 years. This study aims to investigate whether dysregulation of (one of) these mechanisms may underlie RM. Objective of the study: To test The Selection Failure hypothesis by assessing A) the degree of embryo invasiveness and decidual acceptance (the quality of decidualization, endometrium-embryo communication and endometrial stromal cell (ESC) migration) and B) the angiogenic capacity of decidual NK (dNK) cells, in order to elucidate the pattern of the mother-embryo equilibrium in women with RM.
To be diagnosed with recurrent miscarriages, a couple might have a child, however experiences three or more miscarriages, primally this happens during the first trimester. These miscarriages often needs medical evacuation or a D & C. Surgery or retained tissue increases the risk of complications being infection and/or adhesions, known as Ashermans syndrome, which may result in subfertility. Recently chronic infection in the endometrium has been proposed to contribute to the condition, as protocols including treatment with antibiotics have led to birth at term for some of these women. Using the very minimal invasive office hysteroscopy, we aim to describe the uterine cavity in patients diagnosed with recurrent miscarriages regarding both abnormalities in the endometrium and chromic infection.
For implantation of developing conceptus, placental cells need to invade mother's uterus to access maternal blood supply in a control manner. We have found a combination of maternal immune genes (the KIR family) and fetal genes (HLA-C) strongly associated with pre-eclampsia where placenta does not implant adequately. The aim of this research is to investigate these two genes family in women suffering with recurrent miscarriages and find a possible link between them.