Natural Killer Cells – A Cause Of Recurrent Miscarriage?

Natural Killer Cells

Natural Killer cells (NK cells) have an important role to play in the early response to viral infections; they 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 by auto-immune disease.

Recent reports in the media and on the Internet have exposed women to a baffling amount 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 then 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 that populate the uterine mucosa (the inner wall of the uterus) 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 (connective tissue).

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.

Two Types of NK Cells

Here’s something important to note: there’s a huge difference between uterine NK cells and the NK cells that circulate in the bloodstream, and can cause miscarriage.

The best way to explain the difference between uterine NK cells and the NK cells circulating in the peripheral bloodstream is to explain what they do in the body.

Basically, uterine NK cells grow in large numbers to protect the embryo and ensure its development. They are there to attack anything that might try to harm the embryo, such as viruses.

Other NK cells are designed to circulate in the body, via the bloodstream, and are very important in protecting us from viruses and cancer cells.

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.

When the NK cells in the blood stream (not the 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 incoming NK cells do their work.

Sometimes, unfortunately, these cells see the embryo as a foreign organism, so it is attacked and killed.

This is how the problem of recurrent miscarriage arises.

That’s why it is so important that any inflammation in the uterus or pelvic cavity is addressed, so as to solve the problem.

It’s also one of the reasons why any woman experiencing fertility problems should have a laparoscopy, prior to any further fertility treatment. A laparoscopy is the gold standard for addressing and treating any problems in the uterine and pelvic cavity.

In order to get a diagnosis of high levels of NK cell activity in the uterus, a biopsy needs to be done 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 can be done in a doctor’s room and does not require anaesthetic. Unfortunately, it is invasive and inconvenient, but not painful. Most women say the test feels similar to having a pap smear. It cannot be done during an IVF cycle.

Once the biopsy is done, the small amount of endometrial tissue is sent away for genetic testing. Most of the testing in Australia is done in Sydney, as there is really only one lab that does proper processing. The results are usually available after about two weeks.

In Sydney, most of the testing and screening is done through several specialists at IVF Australia, and in Brisbane, only one specialist screens and treats for NK cells.

Specialists in Australia often fail to do this test. This is astounding, given that it’s a very simple procedure that can produce great results and treatment, and provide answers for those who have been enduring the heartache of miscarriage with no explanation.

NK Cells And The Immune System

As mentioned earlier, these naturally occurring cells are immune mediated: they can occur due to an overactive immune system, and inflammation in the body.

This is why immune disorders such as thyroid problems need to be screened for as well.

When investigating thyroid problems, it is important not to screen just for TSH (Thyroid Stimulating Hormone) levels, but also for T3 and T4 levels.

It’s even more important to screen for thyroid antibodies. Many women with the beginnings of thyroid disease have normal TSH levels but can have very high antibody levels.

Treatment for Natural Killer Cells

There is really only one treatment in western medicine for NK cells. It involves the use of steroids, pre and post conception. The main steroid used is prednisone, given in a dosage anywhere from 10mg to 20mg daily.

Steroids, however, have major side effects for the mother and her unborn child.

The way in which steroids dampen down killer cell activity is to suppress the whole immune system. This leaves the mother more prone to infections, colds and flu, and other immune disorders.

The ideal would be to regulate the number of killer cells, rather than use the blanket suppression approach. But to date, this is all western medicine has.

Australia is a leader in NK research, with regard to fertility, and most of the work is being done by Dr Gavin Sacks at IVF Australia.

The good news is that we have access to some fantastic natural products that can help to reduce inflammation and regulate NK cells.

At my clinic, we have seen great results in patients who use these natural anti-inflammatory products. They take them while they are trying to conceive and during pregnancy; there have absolutely no side effects and cause no harm to the pregnancy.

We also have an effective herbal formula we recommend to everyone. It can be taken for colds or flu, 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 clients who come to us with fertility concerns, in case they have undiagnosed Natural Killer cells present.

There are also Chinese herbs that can regulate Natural Killer cells. You will need a consultation, however, before they can be prescribed. The major functions of a prescribed herbal formula are to prevent miscarriage, to increase circulation into the uterine lining to assist implantation, and to help reduce inflammation – the problems caused by NK cells.

Natural Killer cells can be a factor in unexplained infertility, and might 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. I believe this initial investigation can save couples the heartache of going through a miscarriage, especially if Natural Killer cells might be the cause.

Recommended reading: See our article on the MTHFR gene mutation which is also linked to recurrent pregnancy loss.

Articles posted on BellyBelly which are not written by Doctor Andrew Orr are the opinions of BellyBelly and not necessarily the opinion of Doctor Andrew Orr.