Immune related infertility may be one of the underlying culprits behind ‘unexplained infertility’. Having this non-diagnosis is a difficult pill to swallow when you are on a fertility journey. Without a diagnosis, you can’t find a solution. Without having a solution, or even something to work towards, you might feel lost, powerless and somewhat abandoned by medicine.
Immune related infertility is a relatively controversial field. Tests often sample from the peripheral blood – that is looking at the immune cells that are travelling about your body. We know that these are not necessarily the same immune cells that are found in the uterine environment. It is true that we don’t yet fully understand exactly how the immune system impacts fertility and miscarriage. However, let’s look at some of the evidence.
Natural Killer Cells and Immune related infertility
Natural Killer cells are found in the blood. They are part of our immune army that fights off infections, viruses and tumour cells. Elevated NKs are purported to reject a developing embryo, inhibit conception, implantation and cause miscarriage. However the NK cell type found in the uterine environment is different. If you are measuring the type in your blood, and possibly find they are elevated, this may not necessarily mean that the NKs in the uterus are elevated. If we are not looking at the NK cells in the uterus, how we can we be sure this is happening?
A meta-analysis in science is one of the strongest sources of evidence. An excellent meta-analysis was published in 20141 examining the studies on NK cells and their relation to fertility outcomes. This study showed a significant association with elevated NK cells in the peripheral blood of infertile women and those with recurrent miscarriage compared with fertile women. In these analyses, the same associations were not seen for uterine NK cells.
Looking at the whole picture on inflammation
While we know that uterine NK cells and peripheral blood NK cells are not exactly the same, from a functional medicine point of view, we always look at root cause. If you have an inflammatory process going on in your body, we would always work to restore this balance. For example, we do use medicinal mushrooms such as mesima to reduce NK cells. These are highly effective but we will also always take the whole person into account. If there are other inflammatory issues going on, it is worth addressing these at the same time and not just assume that a mushroom supplement is going to do all the heavy lifting. Some examples might include conditions you might relate to your fertility like endometriosis or other conditions such as chronic eczema, asthma, sinusitis, psoriasis and irritable bowel syndrome.
Your diet and lifestyle can also promote inflammation in the body. Increased intake of processed foods, red meat and dairy intake can cause an increase in pro-inflammatory chemical messengers in the body. A sedentary lifestyle and being overweight are also pro-inflammatory conditions. We can help with advice, meal plans and recipes to make changes to support anti-inflammatory mechanisms. This may include increasing oily fish, fruit, vegetables and fibre and optimising nutrient levels such as vitamin D, omega-3 and antioxidants.
Th1/ Th2 imbalance
Another important imbalance in the immune system is between the Th1 and Th2 cells. The immune system is extremely complex, but simply put, the Th1 side targets unknown bodies, fighting off bacteria and viruses. The Th2 side is the allergy side of our immune system. In a pregnancy, we want the balance to tip in favour of the Th2 side. This is so our Th1 side does not fight off the developing embryo, which would otherwise be recognised as ‘foreign’.
If you have elevated Th1 cells or Th1 cytokines (the chemical messengers released by the Th1 cells), medicinal mushrooms may help to calm this. It is worth noting that some mushrooms can make this kind of imbalance worse, as can other plant compounds like turmeric in some cases. We will need to examine test results before recommending a safe and effective protocol. As above, we will also look for the root cause of this activity. What is increasing this Th1 side in the first place?
Very high Th2 is not ideal either
While we want the balance to favour Th2, extreme elevations of Th2 cells are not ideal either. In our extensive experience looking at immune test results, we actually see more people with very high Th2 than we do high Th1. This may go hand in hand with changes in white blood cells numbers (either on a GP test or as ‘total lymphocytes’ on a ZIP test from Sims IVF). This may be due to increased incidences of allergies such as hayfever, rashes and sinus issues or digestive issues caused by food intolerances. We will often look to the gut to investigate why and how the immune system is being aggravated. We then see if we can calm this imbalance from within.
Discuss immune testing with your IVF specialist
We highly recommend discussing immune testing with your fertility specialist if you have had failed IVF cycles, recurrent miscarriage or have been ‘diagnosed’ with unexplained infertility. We are experts in reading these test results and designing effective protocols to address immune imbalances. Please get in touch.
- Seshadri and Sunkara, 2014, Hum Reprod Update 20(3): 429
- Ciara Wright PhD NT did her PhD in the Institute of Immunology, Maynooth University. Hear her talk about her research on fertility and pregnancy here.