Why Can't Taiwan Test for Natural Killer Cells in Fertility Cases? - Obstetrics and Gynecology

Why is it that NK testing is not available in Taiwan (even for self-payment)? (Forwarded from the Director's mailbox)

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Why can't we find hospitals in Taiwan that test for NK cells to prevent the following conditions? This has become a common examination in the United States and mainland China.
Some people in Taiwan send their blood to the U.S.
for testing, but it is time-consuming and complicated due to language barriers.
Most hospitals in Taiwan have the equipment (used for research) but do not conduct clinical tests for patients.
Could we ask the director to help find a hospital where we, a group of women experiencing infertility or multiple miscarriages, can pay out of pocket for testing? Thank you.
Natural Killer (NK) cells exceeding normal levels can lead to mild cases of miscarriage and severe cases of infertility due to interference with implantation.
If this issue is not addressed, undergoing in vitro fertilization (IVF) would be futile.
However, merely testing cell counts is meaningless; we also need to assess cell activity.
For a normal pregnancy, NK cell activity should ideally be below 15%.
Immunoglobulin is the only medication that can effectively suppress NK cell activity, reducing it by about one-third to one-half under normal conditions, but it does not decrease cell counts.
If activity is well-controlled, having a higher cell count is not a concern (meaning a group of inactive cells).
It is important to note that NK cells produce TH1 cytokines, which can be more problematic as they may affect pregnancy.
Currently, it has been found that TH1 cytokines such as interferon (IFN) and tumor necrosis factor (TNF) can interfere with pregnancy.
Mild cases can be managed with immunoglobulin, but there is currently no specific medication for severe cases.
Therefore, to achieve a successful pregnancy, it is essential to control 1) NK cell activity and 2) the ratio of TH1 to TH2 cells.
Typically, NK cell levels peak around 7 to 9 weeks of pregnancy (most miscarriages occur during this time), and then decrease to normal levels around 12 to 17 weeks, so immunoglobulin should be administered at least until the 12-week mark.
According to a report from Weill Cornell Medical Center, approximately 12% of patients with recurrent miscarriages (three or more miscarriages) and 35% of infertility patients (three or more failed IVF attempts) have been found to have elevated levels or activity of Natural Killer cells.
Although there is still some controversy in the academic community regarding the mechanisms and treatments involving NK cells during pregnancy, more infertility centers in the U.S., including the renowned Weill Cornell Medical Center, are willing to conduct or collaborate on such testing and treatment for patients.
The human immune system consists of over 30 types of white blood cells, including neutrophils, monocytes, and lymphocytes.
Some lymphocytes are believed to play important roles in reproductive medicine, including B cells, T cells, NK cells, and CD19+5+B cells.
One subset of NK cells (CD3-CD16-CD56+) helps in the growth of embryonic cells and suppresses the maternal immune system's attack on the placenta.
Another subset of NK cells (CD3-CD16+CD56+) produces TH1 cytokines (including interferon-gamma and tumor necrosis factor-alpha) when activated by interleukin-2.
When these TH1 cytokines are secreted in excess, leading to an imbalance with TH2 cytokines, they are believed to be toxic to the embryo.
TH1 cytokines are originally tools used by NK cells to kill cancerous or infected cells, but when the activity of this subset of NK cells is too strong, they may mistakenly identify the embryo as a foreign invader and launch an attack.
This attack can occur during the implantation phase, leading to infertility, or after implantation, resulting in miscarriage.
What levels of NK cell counts (CD3-CD16+CD56+) and NK cell activity (Natural Killer Activity) are considered harmful to pregnancy? For example, at the Clinical Immunology Lab of the University of Chicago (renamed Rosalind Franklin University of Medicine and Science in 2004), an NK cell count exceeding 12% is deemed abnormal, while the standard range for NK cell activity is 10% to 40%.
However, any value exceeding 15% is considered harmful to pregnancy.
NK patients often have other antibody or autoimmune diseases.
Some patients may only have elevated NK cells, but many have underlying autoimmune conditions, as those with high NK cells frequently present with other antibodies, further complicating their chances of pregnancy.
Common antibody issues associated with elevated NK cells include anti-thyroid antibodies, antiphospholipid antibodies (especially serine and ethanolamine in APA), antinuclear antibodies, anti-sperm antibodies, anti-platelet antibodies, and anti-ovarian antibodies.
Many patients with elevated NK cells also have other autoimmune diseases, which may not directly harm pregnancy, such as rheumatoid arthritis, irritable bowel syndrome, Crohn's disease, psoriasis, and fibromyalgia.
Risks during pregnancy: The most well-known risk associated with NK cells is their interference with implantation and causing early miscarriages.
According to clinical observations by Dr.
Alan E.
Beer, a renowned expert in immunological infertility, NK activity is strongest from embryo implantation until about 9 weeks of pregnancy, which is when most miscarriages occur.
Most patients see NK activity stabilize around 12 weeks, but a small percentage may continue to have elevated levels until 17 to 22 weeks, meaning that patients with high NK cells still face miscarriage risks before 22 weeks.
NK activity rises again after 27 weeks, and if uncontrolled, can lead to severe complications such as preeclampsia and placental abruption, posing significant risks to both the mother and the embryo.
Early pregnancy losses can occur at increasingly earlier gestational weeks, with conditions such as subchorionic hemorrhages visible via ultrasound, blighted ovum with irregular gestational sacs, and mid-pregnancy issues like cervical incompetence and premature rupture of membranes.
In late pregnancy, risks include preeclampsia, placental abruption, and intrauterine growth retardation.

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Fiona, 30~39 year old female. Ask Date: 2005/10/06