Where a couple have several unexplained failed IVF cycles (recurrent implantation failure) or more than 2 miscarriages, and it is not explainable by uterine factors, infections, genetic problems etc, the cause may be due to immunlogical problems. Studies continue to demonstrate that the complex communication between the implanting embryo and the mother’s immune system is critical for pregnancy to succeed. Issues which cause miscarriages or repeat chemical pregnancies may also lead to recurrent implantation failure when they occur at the start of pregancy. In these cases we make a thorough investigation of uterine, sperm, infection and where possible, genetic problems (e.g. karyotyping) but we will also try to find and addresss any immunological or clotting problems.
The mother’s uterine Natural Killer cells have the ability to interact directly with fetal trophoblasts (the cells that form the placenta. Tolerance of the uNKs to the fetus is achieved only by complex biochemical communication between the fetal cells and the mother’s immune system. In some women, the immune defences may be overactive leading to poor tolerance of the embryo and a direct attack on the fetal cells by maternal uNKs. Our strategy is to identify patients who are likely to have these issues and to treat with appropriate medication for reducing uterine immune hostility e.g. steroids, blood thinners, intralipids and GCSF.
In a normal pregnancy the mother’s tendency to produce blood clots in the uterus and placenta is suppressed and the blood flows freely to the baby. However some mothers have a condition called thrombophilia (excessive blood clotting) caused by a variety of genetic or autoimmune reasons. Women diagnosed with thrombophilia and depending on their specific defect, are at between 8 and 40 times higher risk to have implantation failure, miscarriage or even stroke and heart attack compared to the normal population. In most cases, the condition is readily treatable using blood thinning medication.
The mother’s body uses chemical signals (cytokines) to set the alert level for the immune system. In some men and women, levels of inflammatory cytokines like TNFalpha can be very high, which leads to reduced egg and sperm quality and to a more hostile uterus. Our strategy is to identify patients who are likely to have significant systemic and/or uterine inflammation and to treat with appropriate medication for reducing inflammation e.g. steroids, NSAIDs, intralipids, resveratrol, high dose fish oils.
In normal pregnancy, the cells of the mother’s immune system need to recognise the embryo as being foreign cells. This is the first step to producing protective blocking antibodies to shield the embryo from attack by the mother’s immune system. In some women, we find a failure to make antibodies capable of recognising embryonic cells. In the laboratory, as a proxy for embryonic cells we use white blood cells from the male partner on the theory that if the mother’s blood does not carry antibodies to these cells, she is more likely to lack the antibodies that can bind (and allow recognition of) embryonic cells made from his genetic material (the LAD/antipaternal antibody test). In cases where a low LAD is associated with repeat miscarriage, a technique called LIT (lymphocyte innoculation therapy) can be helpful. Alloimmune problems can be particularly severe when the male and female partner have very similar cell surface markers e.g. DQalpha.