I see a lot of clients and have over the past few years been increasingly aware of the area of reproductive immunology. Like most the starting point for this was the book ‘ Is your body baby friendly’ by Dr Alan. Dr Alan Beer is the man behind the whole area of reproductive immunology and the originator of the ‘Chicago protocol’. He set up his clinic as a pioneer and he was instrumental in the fertility world with regards to looking into the immune system as a causative factor to multiple miscarriage and failed implantation. As a result, many IVF clinics started looking at Cytokines, the bodies ‘war’ machine and as I like to call them the ‘ Special forces’ or more commonly know - Natural Killer Cells.
What are NK cells and how are they relevant to pregnancy?
Natural killer cells are under normal circumstances a natural and healthy part of the immune system. They are there to eliminate anything harmful that could cause a threat to your body. They are a type of white blood cell that provides a rapid response to infected cells and go to task particularly if they are needed in the case of tumours that start to form but equally get in there with viruses, parasites and bacteria.
When we get pregnant, NK cells need to get the signal to ‘ power down’ - after all although it is the most natural thing in the world to be pregnant, it is essentially 50% foreign DNA. At the time of pregnancy (and normally the first 12 weeks) the brain needs to give the signal to lower the natural defences of the body, a situation that can understandidly confuse things. It must be really hard for the body's immune system to ignore what looks like a pathogen starting to develop, via the uterus, as during this early time - implantation starts a whole chain reaction where it then starts to establish its own blood supply!
What should happen before an expensive blood test for NK cells
If you have had multiple miscarriages or grade A eggs at IVF and your partners sperm has also been verified as good with no DNA fragmentation, then the next step for me is always a hysteroscopy. This procedure involves taking a biopsy of your uterine lining and the results will show if there is unusually high NK cells. For me this is the most effective way to establish if NK cells are invasive and could be causing miscarriage.
What normally happens…
If you are working with a progressive IVF centre, they may after 3 or more failed IVFs or miscarriages, send off for a raft of blood tests, which cost a pretty penny!
What you need to know before ordering or letting your reproductive specialist lead on some very expensive tests is the difference between blood NK cells and uterine NK cells. Another thing to keep in mind which takes it a little deeper is you should know is that NK Cells are deemed Bright NK, Super Bright and Dim NK cells http://www.jimmunol.org/content/181/3/1869.full.pdf
..’During implantation, CD56 NK cells are reputed to play an important role whereas CD56 NK cells are mostly negatively associated with reproduction'.
In a few studies they found that the proportion of the uterine CD56CD16 NK cells was significantly lower in IVF patients as compared to the controls (6.9 and 13.7% ) The proportion of CD56 NK cells http://molehr.oxfordjournals.org/content/10/7/513.full
In peripheral blood there is no shift in the CD56/CD56 ratio
Blood NK cells are very different to uterine NK cells leading some experts to conclude that “measuring any parameter of NK cells in blood is not useful in trying to understand the cause of reproductive failure” http://humrep.oxfordjournals.org/content/early/2015/12/05/humrep.dev290
The important thing to keep in mind when you have had multiple miscarriages is that the you need to know a little more about these new tests before proceeding to the next stage and what inevitably can then involve more costs. It is my view that a biopsy is the only way to confirm high NK cells which may be causing some issues with implantation and growth of the baby.
1.Gilman-Sachs A, DuChateau BK, Aslakson CJ, Wohlgemuth GP, Kwak JY, Beer AE, Beaman KD. Natural killer (NK) cell subsets and NK cell cytotoxicity in women with histories of recurrent spontaneous abortions. Am J Reprod Immunol. 1999 Jan;41(1):99-105.