Natural Killer Cells
Natural Killer cells (NK cells) have an important role to play in the early response to viral infections, and have also been linked with failure of pregnancy.
Natural Killer cell activity is now known to be a major cause of miscarriage and reduced implantation.
We also know Natural Killer cell activity can be mediated by high levels of stress as well as auto-immune disease.
Recent reports in the media and on the internet have exposed women to a baffling array of conflicting information about tests for NK cells and “cures” for infertility and miscarriage.
Increasingly, clinics are offering tests to measure the number and activity of circulating NK cells.
As a result of these investigations, many women are offered treatments such as steroids, intravenous immunoglobulins, and tumour necrosis factor blocking agents.
Natural Killer cells (identified by the surface marker CD56) are the dominant type of maternal immune cells populating the uterine mucosa during formation of the placenta. These uterine NK cells are also present in the endometrium (uterine lining) of non-pregnant women, when under the control of ovarian hormones. After ovulation, uterine NK cells increase vigorously, so by the late secretory phase, they account for at least 30% of the endometrial stroma.
Uterine NK cells accumulate in large numbers at the implantation site. Here they are in close contact with the invading placental trophoblast cells, which transform the spiral arteries into high conductance vessels. This transformation is essential to ensure a normal blood supply to the fetus and placenta throughout pregnancy.
Something important to note: there's a huge difference between uterine NK cells and the NK cells that circulate in the bloodstream, causing miscarriage.
The best way to explain the difference between uterine NK cells and the NK cells circulating in the peripheral bloodstream is to show what happens to them in the body. Basically, uterine NK cells grow in large numbers to protect an embryo and ensure its development. They are there to attack anything that may try and harm the embryo, such as viruses.
What Causes The Problem?
Here’s the problem: if any inflammation is present in the pelvic cavity or the endometrial lining (endometriosis, PCOS, tubal inflammation etc.), the immune system responds by sending the other NK cells in the blood stream to attack and kill off inflammation. Remember, NK cells are designed to be in the body, and are very important in our protection of viruses and cancer cells.
When these NK cells in the blood stream (not uterine NK cells) reach the site of inflammation in the uterus or pelvic cavity, the uterine killer cells that are protecting the embryo move out of the way to let the NK cells do their work. Unfortunately, sometimes an embryo is recognised as a foreign organism and is attacked and killed off.
This is where the issues surrounding recurrent miscarriage come in. This is also a reason why any inflammation in the uterus or pelvic cavity needs to be addressed to help fix this issue, and one of the reasons why any woman having fertility issues needs to have a laparoscopy prior to any further fertility treatment. A laparoscopy is the gold standard for addressing and treatment of issues in the uterine and pelvic cavity.
As mentioned earlier, these naturally occurring immune mediated cells can occur due to an overactive immune system and inflammation in the body. This is why immune disorders such as thyroid issues need to be screened as well. When screening for thyroid issues, it is important not to just screen for TSH (Thyroid Stimulating Hormone) levels but to also screen free T3 and T4 levels, and more importantly to screen for thyroid antibodies. Many women with the beginnings of thyroid disease can have normal TSH levels but can have very high antibody levels.
In order to get a diagnosis of high levels of NK cell activity in the uterus, a biopsy needs to be undertaken between day 24 and day 28 of a menstrual cycle. This is because NK cells are at their highest levels during this phase of the menstrual cycle. The procedure only needs to be done in a doctor's room and does not require anaesthetic. Most women say the test feels similar to having a pap smear. Unfortunately, this procedure is invasive and inconvenient, but it’s not possible to be done during an IVF cycle.
Once the biopsy is done, the small amount of endometrial tissue is sent away for genetic testing and the results take two weeks to process. Most of the testing done in Australia has to be sent to Sydney, as there is really only one lab doing proper testing. Many specialists in Australia fail to test for this, and it’s astounding given that it’s a very simple testing procedure that can offer great results, treatment and answers to those who have been enduring the heartache of miscarriage with no explanation. In Sydney, most of the testing and screening is done through several specialists at IVF Australia, and in Brisbane, there is really only one specialist screening and treating for NK cells.
Treatment for Natural Killer Cells
There is really only one treatment in western medicine for NK cells, and it involves the use of steroids at pre and post conception. Prednisone is the main steroid used and is given in a dosage anywhere from 10mg-20mgs daily. However, steroids can have major side effects on the mother and unborn child. Steroids also suppress the whole immune system and dampen down killer cell activity this way. This also leaves the mother more prone to infections, colds and flu and other immune disorders. The key is regulating the amount of killer cells rather than using blanket suppression approach. But to date, this is all western medicine has. Australia is the leader in NK research with regards to fertility, and most of the work is being done by Dr Gavin Sacks at IVF Australia.
The great news is that we have access to some fantastic natural products that can help with reducing inflammation and regulating NK cells. At my clinic, we have seen great results from our patients who are using these natural anti-inflammatory products. They are taken while trying to conceive and during pregnancy, with absolutely no side effects or harm to the pregnancy. We also have an effective herbal formula that we recommend to everyone for colds or flus, which can be taken for immune support and as a preventative. It dampens down inflammation and helps to regulate NK cell activity. We’ve started to recommend this treatment to all fertility clients, in case of the presence of undiagnosed Natural Killer cells.
There are also Chinese herbs that can regulate natural killer cells. The ConceptShen Nutritional Medicine formula called ‘Nourish’ helps with inflammation and NK cell regulation. Its major function is to prevent miscarriage and also increase circulation into the uterine lining to assist implantation.
Natural Killer cells can be present in unexplained infertility and may be more prevalent in those with autoimmune disease or other inflammatory conditions such as endometriosis, tubal disease and PCOS (polycystic ovarian syndrome).
In my clinic, I screen my fertility patients for NK cells, especially those who have had recurrent miscarriage, because I believe it should be an initial investigation to save couples the heartache of going through a miscarriage, especially if Natural Killer cells may be the cause.
Recommended reading: see our article on the MTHFR gene mutation which is also linked to recurrent pregnancy loss.