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Do Elevated Natural Killer Cells Cause Recurrent Miscarriages?

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Updated June 13, 2014

Case For

It would be hard to dispute that NK cells can be elevated in women who have recurrent miscarriages, as numerous studies have found this to be true. Scientists have fleshed out a few mechanisms in which elevated NK cells could terminate an otherwise viable pregnancy, usually with the idea that a disordered immune system is causing the cells to attack the pregnancy. At least one study has found evidence that NK cells in the uterus do attack cells from the pregnancy in cases of spontaneous miscarriage, although it's unclear what those results mean.

Some researchers have even controlled for the chromosomes of the miscarried pregnancy to determine whether the NK cells were elevated because of the body's natural response to a chromosomally abnormal pregnancy, and they have found that women with elevated NK cells were potentially more likely to go on to miscarry a chromosomally normal baby in their next pregnancy.

If true that these elevated NK cells are causing viable pregnancies to miscarry, the idea would be that reducing elevated NK cells should lead to reduced risk of miscarriage. Proponents of this theory sometimes prescribe immune suppressing medications such as prednisolone to women with unexplained recurrent miscarriages and elevated NK cells, an approach that has been shown in at least one study to reduce the levels of NK cells. One widely reported 2008 study claimed evidence that this approach led to 75% of study participants carrying their next pregnancies to term, and the researchers suggested that elevated NK cells could be behind as many as one-third of all cases of unexplained miscarriages.

Case Against

There are plenty of alternative explanations for the finding of elevated NK cells in women with recurrent miscarriages -- and especially the idea that the elevation is a cause rather than a chance finding associated with miscarriages.

For starters, there is evidence that stress can cause fluctuations in NK cells. An interesting 2006 study found that women with recurrent miscarriages could have elevated NK cells in a first of two blood draws -- but then in a second blood draw 20 minutes later, they could show no elevation of NK cells as compared to women with no history of miscarriage. The researchers speculated that there was a chance that some women tended to have an immune system that responded more readily to stress, which might tie in with some other research showing correlations between stress and miscarriage.

Perhaps most importantly, there are many gaps in understanding of how NK cells affect pregnancy -- and researchers have yet to find compelling evidence that any kind of immune-suppressing therapy actually works to reduce miscarriage rates. Although many proponents of these NK cell reduction therapies point to findings showing that 75% of patients go on to carry successful pregnancies after the immune treatment, there's a lot to be said for the placebo effect given that other research exists showing that about that same number of women will go on to have successful pregnancies merely with supportive care and no specific treatment.

Where It Stands

Despite the headlines that occasionally enter the media, no medical organization formally recommends testing for and treating NK cells in women with recurrent miscarriages and there is a lot more research that needs to be done before anyone can truly recommend steroids or immune suppressants as a recurrent miscarriage treatment. Any treatment for elevated NK cells should be considered experimental at this point.

That being said, when you're having miscarriage after miscarriage, you may be willing to try just about anything whenever there's a chance that it might work. If you are pursuing immune system therapies for elevated NK cells, just be sure that you understand the uncertainties in the research and be sure to work with a practitioner who isn't making you any unreasonable promises about what you are getting into -- and be sure to think carefully before spending a lot of money on this kind of treatment, especially if you have limited financial resources.

Sources:

Dosiou, Chrysoula and Linda C. Giuduce, "Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives." Endocrine Reviews Sept 2004. Accessed 10 Sept 2008.

Moffett, Ashley, Lesley Regan, and Peter Braude, " Natural killer cells, miscarriage, and infertility." BMJ 2004. Accessed 10 Sept 2008.

Nakashimura, Akitoshi, Arihiro Shiozaki, Subaru Myojo, Mika Ito, Mikiko Tatematsu, Masatoshi Sakai, Yasushi Takamori, Kazuyuki Ogawa, Kinya Nagata and Shigeru Saito, "Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion." American Journal of Pathology Aug 2008. Accessed 10 Sept 2008.

Quenby, Siobhan, Chimwemwe Kalumbi, Michelle Bates, Roy Farquharson and Gill Vince, "Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage." Fertility and Sterility May 2005. Accessed 10 Sept 2008.

Shakhar, Keren, Ella Rosenne, Ron Lowenthal, Guy Shakhar, Howard Carp, and Shamgar Ben-Eliyahu, "High NK cell activity in recurrent miscarriage: what are we really measuring?" Human Reproduction May 2006. Accessed 10 Sept 2008.

Yamada, Hideto, Emi Hirayama Kato, Yasuhiko Ebina, Shigeki Shimada, Mamoru Morikawa, Noriaki Sakuragi and Seiichiro Fujimoto, "High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion." American Journal of Reproductive Immunology Dec 2003. Accessed 10 Sept 2008.

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