Can natural killer cells cause infertility?

This we are doing quite often, especially after 1-2 unsuccessful transfers of good quality embryos without other conditions which can explain why a woman does not become pregnant. We discovered that around 30 – 40 % in this category of patients have increased NK cell activity and we are using intralipid infusions to decrease this activity 4-5 days before the embryo transfer.

The immune system is rather complicated. Now, natural killer cells (which is the full name for NK cells) form a part of our body’s immune system. They normally help the body fight infection and even cancer and every organ has NK cells to protect it. Amongst the various organs, the uterus has got NK cells. So NK cells are in our body and NK cells are in the uterus. The NK cells present in the uterus are known as uterine NK cells and they’re very very important when the uterus is preparing for pregnancy, for implantation. In order to facilitate blastocyst implantation, the lining of the uterus, the lining of the womb, needs to be inflamed slightly so that the embryo can implant and the uterine NK cells play a very important role during the process of implantation. However, as everything in life, if there are too few or too many uterine NK cells that could affect the normal environment, if there are too few NK cells, then it is possible that any embryo -even an abnormal one, can implant. Hence why some women have 10, 12 ,15 miscarriage even abnormal embryos would implant. If there are too many uterine NK cells, then that makes the implantation process very difficult because that uterus is very much protected by the NK cells, so what we need to realize is the right balance of the presence of uterine NK cells that facilitate implantation.

Actually the way to look at it is as a whole picture because if we point the gun to one cell and forget about the dynamics of the body and this miracle so we are missing a lot. Natural Killer cell, anti-inflammatory, antioxidant – I did a study in 2010 about total antioxidant capacity on the follicular fluid between agonist and antagonistic protocol. I’m just checking the total antioxidants, not only the oxidative stress or the antioxidants because we can give antioxidants and affect the oxidative stress – we need the oxidative stress but in a certain portion. This is the problem with probiotic, prebiotic, given antibiotics. We can give antibiotics that will kill beneficial cell bacteria that will help implantation. We can give probiotics in an overdose that will not have any benefit and we do not know will it harm or benefit. So this is the dilemma of Natural Killers. Natural Killer cells are a single element from many many factors. If it’s not already good, interleukin is another problem, inflammatory markers all are another dilemma, so if you have this problem, what I will suggest – change something like an anti-inflammatory diet (I mentioned before). It can help to regulate your homeostasis – homeostasis, I mean, your body adaptability, your immune system, everything in your body. This is a problem – if you are pointing at one thing, you are just putting your head in the sand.

From our experience there is not only high number of Peripheral NK cells there are 3 markers if the two markers: Peripheral NK cells, Endometrial NK cells high and the activity is higher that references that are established in international bibliography, I don’t think that there is chance for the lady to conceive or to have even successful IVF trail. We see many cases. I can give you an example: a 49 years old lady and husband was 63 years old – they proceeded with the donor’s embryo. They did 12 IVF trials in IVF Center with donors’ embryos and when I tested the lady, her endometrial NK cells were high – one number that I have never seen in my entire career so far. Then we provided 2 infusions with intralipids and after one month, we did the screening test checking the level of endometrial NK cells. When we confirmed that the number was decreased significantly, then we did one more dose of infusion and we confirmed that they can proceed with IVF treatment in the same center but without notifying the center what procedure we did. Then we had the fantastic outcome: 49 years old lady who was never pregnant and now she has a 3 or 4 years old baby girl that she is carrying for. That was a very specific case to induce the significance of NK cells in reproductive immunology.

What I do believe is that, yes, immunology does affect fertility a lot. I believe that there is a strong association between raised NK levels and failed implantation or even recurrent miscarriage. I do believe that. Many people defer or have skepticism on is: what is the correct treatment. I don’t think we’re anywhere close to knowing what the correct treatment is. People have tried treatment using steroids, using intralipids to try and suppress the immune system. There have not been many studies that have shown definite improvement in success rates when these two are applied. On top of that, we’re in the middle of a Covid pandemic, suppressing a woman’s immune system when you’re not even sure of the of the chances of success, is difficult to justify in the light of the current pandemic we’re in and so, we see it’s i’d say there’s still a lot we need to learn about the immune system and how it actually affects fertility. I believe it does but we need to know how it actually does affect and what are the correct measures to use because some of these measures can be actually harmful to the woman or the baby. Things like steroids, the intralipids and steroids first of all suppress the immune system and also they can lead to a hyperglycaemic environment in the woman who’s taking them and this can lead to big babies because this can lead to high amounts of insulin and glucose that can make make babies increase in size ​un​natural and also developed diabetes later in their adolescent and adult lives. That’s why there is a bit of skepticism. It is an interaction that we see but we don’t yet know how to properly treat.

Uterine Natural Killer (uNK) cells form the major leukocyte population in the endometrium at the time of implantation and have received considerable attention in relation to their role in normal implantation and early placental development.
In cases of pregnancy loss, there is a regular pattern involving predominant Th1-type, in other words pre-inflammatory immunity profile, a decrease in T-regulatory cells and an increase in NK cells population. Abnormal numbers and dysfunction of the decidual NK population could result in pregnancy loss as it has been suggested by studies that quantify Natural Killer population changes as they are reflected in peripheral blood. Nevertheless, we must always remember that it remains controversial whether peripheral blood measurements reflect conditions at the placental bed.