Recurrent miscarriages: Causes, treatment and consequences.

With 1 to 2% of the couples suffering from recurrent miscarriages, prevention would be of undisputable benefit for couples who suffer from recurrent miscarriages on a medical as well as psychological point of view. Understanding mechanisms triggering the maternal immune system in more detail, especially at the maternal-fetal interface, could help to elucidate mechanism behind recurrent miscarriages. An inadequate peripheral maternal immune response against paternal antigens may lead to improper implantation and rejection of the embryo. Both HLA genes and cytokines have been studied extensively in women with recurrent miscarriages. So far no study has focussed on the specific immune response and cytokine production by maternal PMBCs to paternal or umbilical cord cells in couples with recurrent miscarriage. The outcome of these functional studies will be related to HLA analysis of both partners and the newborn. Hopefully these results will give us new insights and possibilities for development of various treatments.

The fetus is protected from maternal immune responses through various mechanisms such as lack of expression of classical HLA class I and class II molecules, inhibitory T cell, costimulatory molecules, NK cells, complement regulatory proteins by trophoblasts, and by local maternal regulatory T cells.

We hypothesize that an imbalance between immunomodulatory and effector cells and as a consequence an inadequate cytokine production could be responsible for recurrent miscarriage. This study will include couples with recurrent miscarriages. A prospective study will be performed during the following pregnancy by taking peripheral blood samples, which will be stimulated with paternal, third party (unrelated PBMCs) and, if available cord blood cells expressing HLA-antigens, and monitored for cell proliferation, cytokine production, antibodies and complement activation to determine the difference between ongoing pregnancies and miscarriages.

01-12-2011: Start recruiting couples at miscarriage clinic;

01-03-2012: Start first labexperiments;
01-01-2013: Start analyzing results;

01-01-2014: Finishing study.

N/A