Stressed Uterine Cells & Inflammation Cause Miscarriage, Not Natural Killer Cells

It is stressed uterine cells and inflammation causing miscarriage and causing the embryo not to implant, not Uterine Natural Killer cells.

For the first time the functions of natural killer cells in the womb have been identified by Researchers at the University of Warwick and University Hospitals Coventry

Although it has long been known that the lining of the womb harbours dynamic uterine natural killer cells, no functions have so far been given to these cells outside of pregnancy.

The researchers have discovered that the uterine natural killer cells remodel and refresh the lining of the womb at the time of embryo implantation. This is the first time a role for uterine natural killer cells in the lining of the womb has been identified outside of pregnancy. The research was published on December 14, 2017.

In addition they discovered that this process isn’t always balanced in each cycle. The natural killer cells perform the role of targeting and clearing inflammatory stressed cells, thereby making space for the implanting embryo. However sometimes not enough of these cells are cleared away and sometimes too many are targeted and removed. Excessive inflammation or insufficient clearance by uterine natural killer cells makes miscarriage more likely.

For many years I have been trying to tell people that they need to stop trying to get rid of the natural killer cells, or reduce their numbers. I have long known that natural killer cells are meant to be in the body and their job is to protect us from infections, bacteria, cancers, tumours and inflammation. If killer cells are in high numbers, it means that there is something wrong and that is what needs to be treated, not the killer cells. But unfortunately, many clinics play on couples emotions and the use of the word “Killer”. So then we get this war on killer cells and people wanting to kill the killer cells because they think it is killing their babies. No matter how hard I have tried to explain it, people just don’t listen and now it is finally great to have the research to back up what I knew all along, plus additional knowledge of how Killer cells actually help with implantation and reducing miscarriage.

The researchers have explained what happens if the natural killer cells cannot do their job properly, or there is inflammation that they haven’t been able to target. They said that a good analogy is Swiss cheese: without holes, the embryo has nowhere to go which will cause implantation failure; but if the holes are too large, the tissue will physically collapse and lead to miscarriage. This imbalance, which may be short-lived or last for multiple cycles, explains the high rate of early pregnancy failure. It really can be a numbers game on how long that cycle could last and why it is important to make sure there are enough natural killer cells there to do their job properly. Without the natural killer cells, there is more chance of inflammation and stressed uterine cells being left behind, which will then lead to higher pregnancy loss and reduced implantation.

The researchers conducted an analysis of 2,111 endometrial biopsies, which is more than had ever been conducted previously. The research team examined the acutely stressed cells in the lining of the womb which generate tissue inflammation. They found that the natural killer cells which are in the womb perform the important function of selectively targeting and eliminating acutely stressed cells.

When there are high acutely stressed cells in the lining of the uterus, the lining of the uterus fails to sense the chemical signals from the fertilised egg and it then silences many of the genes involved in allowing the embryo to implant and embed into the uterus.

One of the chemicals needed for this process to take place is Trysin, which is a common enzyme the embryos gives off. If trysin isn’t detected the embryo is not accepted and left to disintegrate and then the cycle is reset once again. The lack of Trysin signal appears to indicate to the endometrium that the quality of the embryo is not very high and initiates a reduction of receptivity to implantation. These findings could help to improve the success rates of IVF, because one of the biggest problems with IVF is getting the embryo to implant

The research team also found that high numbers of Natural Killer cells in the endometrium are not only a sign of high inflammation and acutely stressed uterine cells, but also indicate a insufficient production of steroids, which in turn leads to reduced formation of fats and vitamins that are essential for pregnancy nutrition.

Again, this is exactly what I have been trying to say for years and why when I treat women who are having implantation issues and recurrent miscarriage I look at treating the cause of the issue, rather than masking it.

To treat miscarriage and help with embryo implantation you need to do the following

  1. Reduce inflammation in the uterine environment and pelvic cavity
  2. Make sure the pelvis, tubes and uterus have been surgically evaluated properly prior to conception, or assisted reproduction (IVF, IUI, ICSI etc)
  3. Increase blood flow and nutrients into the uterine lining
  4. Ensure adequate essential fats and nutrients are given prior to conception
  5. Reduce stress levels
  6. Increase protein and reduce inflammatory refined carbohydrates
  7. Make sure the couple in are optimum health (healthy sperm + healthy eggs=health baby)
  8. Make sure the man is being treated at the same time the woman is (up to 85% of miscarriage issues are related to chromosomal and DNA factors related to poor quality sperm, which cannot be measured by a normal semen analysis)

We need to stop blaming high NK cells as being the cause of miscarriage and embryos not implanting. We need to look at the real cause, which is inflammation, stressed uterine cells ( due to stress in the person), lack of nutrients and blood flow in the uterus and lifestyle factors that is also leading to increase miscarriage rates and reduced embryo implantation. This is why I have my own range of fertility formulas to assist the uterine environment and help with implantation.

Let’s not forget that faulty sperm and DNA damage and chromosomal issues with sperm are also a big part of miscarriage too. Miscarriage is not just a woman’s issue. To be honest, statistically it is more likely to be on the male side of the equation and often gets overlooked. But that is a whole other post in itself.

This is why I offer a comprehensive fertility program that looks at every aspect of the couple and every aspect of fertility. It is also why I have helped over 12,500 babies into the world. It is about my motto of “No Stone Left Unturned” and treating the cause of people’s issues, not just guessing and trying to treat the symptoms as you go along.

Hopefully in the future this new information will be used to screen women at risk of reproductive failure and help with new treatment options for women suffering recurrent miscarriages or recurrent IVF failure.

If you are having trouble conceiving and want answers to your fertility issues, then maybe it is time to book into my fertility program and get some real answers, real treatment and get the baby you so desperately deserve.

Regards

Dr Andrew Orr

Reproductive Medicine & Women’s Health Medicine Specialist

-The International Baby Maker

-No Stone Left Unturned

The Truth About Natural Killer Cells & Miscarriage

On a daily basis we get people, who are having failed IVF cycles, calling my clinic looking for some miracle pill, to supposedly eradicate the body of natural killers cell and wipe them off the face of the planet in some war like rage, all because they have been told this will bring an end to their fertility woes.

I wish it was that easy and when my staff go on to explain that treating natural killers cells (uterine killer cells), and especially looking at the cause of natural killer cells (uterine killer cells), is complex, there is no one miracle cure, nor some magic pill, people get annoyed and hang up the phone in a huff ,without listening to the reasons why.

One of the things I always say, when people ask me about regulating natural killer cells for fertility purposes, is “How long is a piece of string?”

This is because this subject is very complex and there are many reasons why natural killer cells may be impacting implantation. So, hence the response is always going to be “How long is a piece of string?”

While Natural killer (NK) cells have an important role in the early responses to viral infections, they have also been linked with failure of pregnancy.

Increasingly, clinics are offering blood tests, at an increased cost to the patient, 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. The scientific rationale for these tests and treatments, however, is not always supported by our current knowledge of the function of uterine NK cells.

So, I thought it was about time I set the records straight on the BS information, that seems to being handed around as gospel, by money hungry fertility clinics run by big health conglomerates, and by the rotten Dr Google, about natural killer cells (uterine killer cells) and these supposed miracle pills, that will miraculously fix someone’s fertility issues.

Let’s Look at the Facts about Natural Killer Cells Relating to Miscarriage

  1. There is no miracle pill, or one supposed miracle treatment, or a one pill solution to treat, or get rid of natural killer cells. You do not want to get rid of NK Cells.
  2. Natural Killer Cells are a natural part of the immune system designed to target inflammation, kill of cancer cells, kill off bacteria and protect the body from harmful invasion of foreign organism
  3. There is huge difference between natural killer cells that are circulating in the blood stream, compared to uterine killer cells
  4. Uterine Killer Cells are in large numbers during a pregnancy to protect the embryo
  5. Natural Killer Cells are only in large number and are only being sent out by the immune system because there is some inflammatory process going on in the pelvis, or the rest of the body
  6. You cannot regulate Natural Killer Cells numbers unless you first address the inflammatory process that is causing them to be in high numbers in the first place (Eg- Inflammatory gynaecological conditions such as PID, Endometriosis, PCOS, Adenomyosis, Adhesions, STI’s, CIN, HPV, Herpes etc)
  7. Many people have not had the proper initial fertility investigations and testing needed to actually fall pregnant in the first place and looking at Natural Killer Cells, before all that proper testing etc is done, is actually not assessing the patient properly.
  8. If you do not treat the cause of the Natural Killer Cells being in high numbers, you will not be able to reduce the numbers of Natural Killer Cells that are actually doing the job they are meant to do, which is …. Protect the Body.
  9. Many of the so called treatments for Natural Killer Cells, regarding fertility, have never been approved for such treatment and research on it is still inconclusive.
  10. Some of the treatments being proclaimed as miracle cures (Intralipids etc) are purely money making exercises that are preying on the vulnerability of people who have been told wrong information and have this perception of some killer being inside their body attacking their embryos.
  11. Intralipids have never been proven to treat Natural Killer Cells and are derived from highly inflammatory soy based compounds, which then in turn can cause more inflammation.
  12. The drugs used in the treatment of Natural Killer Cells are steroidal based and carry many side effects and are for more harmful to the body that any natural killer cell will ever be. The steroids are also a category C drug that has been shown to have an effect on the neonate
  13. Steroids, such as Prednisone, do work on regulating NK cells, but they do so by suppressing the immune system, thus compromising a person’s immunity. There are also risk to peoples minerals by using these long term and there are also other side effects to the body.
  14. Natural Killer Cells are there to protect the body, not hurt it.
  15. Natural Killer Cells are only attacking embryos because they are seen as foreign body as well and when they are there trying to kill of the diseases and issues causing inflammation in the body, they just happen to kill of any other foreign organism and inflammatory processes at the same time
  16. Again, to address natural Killer Cells, you need to address the inflammatory process as to why they are in high numbers in the first place
  17. The perception around Natural Killer Cells being this “thing” killing off embryos in the body is misguided and is actually not a true representation of what Natural Killer Cells actually do. It is purely often used to tug on the heartstrings of unsuspecting patients, who are highly emotive and clinics use these emotions to get them to pay for treatments that have never been fully proven to work.
  18. The name “Killer Cell” is too often exploited in the wrong context by many in the fertility world
  19. Blood tests cannot measure the number of Natural Killer Cells in the Uterus, Only a biopsy can do this.
  20. A Natural Killer Cell (uterine killer cells) Biopsy has to be done between the 24th and 28th day of your menstrual cycle to give the best results.
  21. Blood tests can only measure the circulating NK cells in the body and not the uterine killer cell activity, which can be the cause of recurrent miscarriage. So, if you have had a blood test, it is not measuring what is needed. Everyone will have circulating NK cells in their blood stream.
  22. The percentage of CD56+ NK cells in peripheral blood in normal healthy individuals varies from 5% to 29% (2)Despite this, more than 12% NK cells in women with infertility or miscarriage has been arbitrarily defined as abnormally raised and used as an indication for treatment (4)
  23. The percentage of NK cells in blood can be affected by many factors including sex, ethnicity, stress, and age too.

Natural Killer cells (Uterine killer cells and other NK cells) are the main immune cell-type found in the uterus. Their numbers increase through the menstrual cycle to peak at the time of implantation. If an embryo does implant, NK cell numbers increase further to 70% of all cells.

Uterine NK numbers start to decrease at around the 20 week mark of pregnancy and are all but absent at the end of pregnancy.

Natural killer cells acquired their name as a result of the initial test used to identify them in vitro. Unlike T lymphocytes, NK cells are able to spontaneously kill cells in a non-MHC restricted manner.

Regrettably, this is a misleading name in reproduction, and the powerful image of maternal cells attacking the fetus is emotive and easily exploited. None the less, these NK cells can kill off the embryo at early stages of pregnancy, but there is nearly always a reason why. That reason is inflammation in the pelvic cavity and uterus. This needs to be addressed to regulate the number of NK cells, not some notion of killing off the “Killer Cells”.

Types of Inflammation causing high Natural Killer Cells (Uterine Killer Cells)

  • Endometriosis & Adenomyosis
  • PCOS/PCO
  • Fibroids, Myomas
  • Vaginal Infections & Bacteria
  • STI’s
  • Cancer, Trauma, Localised Lesions & Others
  • Stress

Yes, stress can lead to a compromised immune system, which then leads to high TNF (Tumor Necrosing Factor) and increase Natural Killer Cells, which then leads to prolonged increase activated T Cells, and this then causes reduced implantation of embryos.

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 be investigated and treated properly. This needs to involve proper differential diagnosis, proper pathology testing, genetic testing and surgical investigations such as 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.

Natural Killer Cells (Uterine Killer Cells) can be a part of recurrent miscarriage, but we need to stop the misinformation and perception of them being some killer organism that isn’t meant to be in the body. They are meant to be in the body and the name is all too often exploited by many to offer unproven treatments and medications by clinics trying to increase profits.

If you want to regulate and treat natural killer cells (relating to recurrent miscarriage) properly, you need to find out what is causing them to be there in the first place. There is no magic pill to get rid of Natural Killer Cells. You cannot rid the body of Natural Killer Cells anyway. They are meant to be there. You can only regulate the amount of killer cells doing their job and you need to find out why they are in higher numbers in the first place. This is usually because there is some sort of inflammation, infection, bacteria, or malignancy going on in the body that has not been investigated properly in the first place. Let’s not forget that stress, yes stress, increases the amount of Natural Killer Cells in the body too.

At my clinic, I have a proper Natural Killer Cell protocol and treatment plan that is individually tailored and looks at the “cause” of high number of Natural Killer Cells and makes sure that proper investigations, testing and treatment are administered to treat the person properly. This can also be done alongside current medical protocols such as the Bondi protocol, or California protocol.

Regards

Dr Andrew Orr

(Reproductive Medicine & Women’s Health Medicine Specialist)

-The International Baby Maker

-No Stone Left Unturned

References

  1. Moffett-King A. Natural killer cells and pregnancy. Nat Rev Immuol 2002;2: 656-63.[CrossRef][Web of Science][Medline]
  2. Pijnenborg R, Vercruysse L, Hanssens M, Van Assche A. Incomplete trophoblast invasion: the evidence. In: Critchley H, MacLean A, Poston L, Walker J, eds. Pre-eclampsia. London: RCOG Press, 2003: 15-2615. Parham P. NK cells and trophoblasts: partners in pregnancy. J Exp Med 2004;200: 951-5.[Abstract/Free Full Text]
  3. Hiby SE, Walker JJ, O’Shaughnessy KM, Redman CWG, Carrington M, Trowsdale J, et al. Combinations of maternal and paternal innate immune genes influence the risk of pre-eclampsia. J Exp Med 2004;200: 957-65.[Abstract/Free Full Text]
  4. Aoki K, Kajiura S, Matsumoto Y, Ogasawara M, Okada S, Yagami Y, et al. Preconceptional natural-killer-cell activity as a predictor of miscarriage. Lancet 1995;345: 1340-2.[CrossRef][Web of Science][Medline]
  5. Ntrivalas EI, Kwak-Kim JY, Gilman-Sacchs A, Chung-Bang H, Ng SC, Beaman KD, et al. Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology. Hum Reprod 2001;16: 855-61.[Abstract/Free Full Text]
  6. Bisset LR, Lung TL, Kaelin M, Ludwig E, Dubs RW. Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland. Eur J Haematol 2004;72: 203-12.[CrossRef][Web of Science][Medline]
  7. Kwak JY, Kwak FM, Gilman-Sachs A, Beaman KD, Cho DD, Beer AE, et al. Immunoglobulin G infusion treatment for women with recurrent spontaneous abortions and elevated CD56+ natural killer cells. Early Preg 2000;4: 154-64.
  8. RCOG Scientific Advisory Committee. Immunological testing and interventions for reproductive failure. London: RCOG, 2003. (Opinion paper 5.)
  9. Scott JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 2003;(1): CD000112.
  10. Daya S, Gunby J, Clark DA. Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis. Am J Reprod Immunol 1998;39: 69-76.