Recurrent miscarriages and failure of implantation after transfer of good quality embryos in IVF treatment are the two major challenges in reproductive medicine. In the past decade considerable efforts have been made to identify possible immunological causes for these challenges through reproductive immunology.
Although your immune system is designed to fight infection and eliminate foreign organisms to prevent you from becoming unwell, it's also understood that it may promote or prevent a normal pregnancy. The most extensively studied group of immune cells are a type of lymphocyte (white blood cell) called natural killer cells (NK cells), they act as frontline in the protection mechanism of the body to attack infection and potential cancerous cells and are the most abundant immune cell in the uterine lining after ovulation.
Our reproductive immunology research team at The Lister Fertility Clinic, led by Dr Yau Thum, has been involved in research in the area of natural killer cells and immunological aspects of recurrent failed implantation since 2003 and have published papers demonstrating that an "overactive" immune system may negatively affect pregnancy outcomes and IVF success rates.
Who should be tested?
Failure of implantation, as well as recurrent miscarriage, is not due to a single problem and therefore it is unlikely to have a single solution. This remains a controversial area and such tests are not recommended as routine. Natural killer (NK) cell testing is not offered to all patients starting IVF treatment as in the majority of cases it is the abnormal genetics of the embryo that causes a failure to implant. However, further developments in reproductive immunology testing and treatments may at least help eliminate one of the variables that may cause such tremendous emotional burden on the couples involved.
NK testing may be discussed at consultation with patients who have a history of repeated failed IVF attempts and/or repeated early pregnancy loss. It may also be discussed with patients with a history of endometriosis with previous failed IVF cycle/s, history of known autoimmune disorders (such as Lupus, Rheumatoid arthritis, Crohn's disease, ulcerative colitis, Ankylosing Spondylitis, Thyroiditis, Chronic fatigue syndrome etc). Before recommending immune testing or treatment you will be fully counseled by your consultant.
What can be tested?
Natural Killer Testing
There are 3 steps to the NK cell blood test:
- NK cells number (activation marker CD-69)
Women may have large number of NK cells but if they are not activated, it is thought they will be unlikely to have a negative impact on reproduction. At The Lister Fertility Clinic, we measure the levels of "active" NK cells in the blood that carry the CD-69 activation marker which, if raised, we have shown to have a negative effect on outcome.
- NK cells cytotoxicity assay
We also directly measure how toxic your NK cells are by adding them to pregnancy-like tissue in our laboratory and measuring the level of "cytotoxicity". If the NK numbers or cytotoxicty is high, we consider immune therapies.
- NK cells cytotoxicity treatment test
The second step in the cytotoxicity assay involves adding the available potential treatment options (IVIg, steroids or intralipid) to see if the killing power of the NK cells can be reduced by the medications. This part of the test helps to determine what treatment to offer the patient.
Cytokine testing (Th1, Th2)
Th1 and Th2 cells are immune cells whose balance is vital for maintaining pregnancy. If you are producing too many Th1-type immune cells this may also reduce the chances of successful implantation and we may again recommend immunosuppression treatment.
Some women may produce an antibody (thyroid peroxidase antibody or TPOab), which may affect hormone production of the thyroid gland. Studies have demonstrated that patients with high TPOab levels or abnormal thyroid function have been found to have a much higher risk of miscarriage.
At The Lister Fertility Clinic we recommend all patients have their thyroid function checked before commencing IVF and fertility treatment and, in some, may also recommend TPOab screening. If abnormal thyroid function is found, treatment during IVF with thyroxine has been shown to reduce the chance of miscarriage.
hCG receptor autoimmunity
hCG is a hormone produced in early pregnancy and there is evidence that it causes natural suppression of the immune system in order to assist in the implantation of the embryo in the womb. A receptor is a part of a cell that attaches to the hormone to have an effect. A theory exists that the presence of maternal antibodies against hCG or its receptor may affect implantation, leading to failure to achieve a pregnancy or to miscarriage.