Most cells of our body have protein markers on their surface called Human Leukocytes Antigen (HLA). These antigens are made by instructions from our genes in our DNA. We have two sets of HLA genes, one derived from our mother and one from our father. Our immune system recognise what is ours and what is foreign by recognising these antigens on the cells. During organ transplants, it is better when the donor’s HLA is similar to the recipient to reduce the chance of rejecting these organs. However, the embryo, which is a foreign body to the mother, needs to have different HLA types to the mother to implant and grow.
Specifically a shared part of HLA system called DQ alpha between the embryo and the mother will not allow the mother’s immune system to recognise the embryo as pregnancy and it will be attacked as foreign body. If the partners have one HLA-DQa gene in common (partial matching), 1 out of 2 sperms will contain a matching gene to the mother. This results in one out of every two embryos expressing that matching trait. This is common. However, if there is total HLA-DQa matching, every single sperm and every embryo will contain a matching gene to the mother.
When an HLA-DQa matching embryo reaches the uterus, it will activate the immune cells (natural killer cells). Implantation for future embryos will be compromised and the woman will either not conceive or will miscarry in the 1st trimester. The more the couple try and more pregnancies occur, the more activation in the natural killer cells.
How is the test done?
This is a blood test done for both the prospective mother and the prospective father.
Outcome of the testing and treatment options:
It is important to realise that in the absence of uterine NK cell activation during first pregnancy, the implantation potential of DQa matching embryos is not compromised. This explains why many woman will present with infertility or recurrent miscarriage after having had one or more prior pregnancies.
In case of partial DQa matching combined with activated NK cells, for viable pregnancy to occur, the embryo should not express the matching husband derived HLA-DQa (50% chance). Adding to it, intralipid, steroids or IVIG treatments should be administered in advance to down-regulate activated uterine NK cells and then re-administered every 2-4 weeks until 20 weeks of pregnancy.
In case of total DQa matching combined with activated NK cells, the likelihood of successful implantation is very low. The only way to bypass the problem is to use a gestational surrogate or if biological mother to-be wants to carry the baby, non DQa matching donor sperm should be considered.