The Killer Question: How to Reduce the Risk of Miscarriage

An estimated one in four women will experience a miscarriage in her lifetime with a quarter of pregnancies ending in the first 23 weeks. These statistics are heartbreaking, and yet the cause of pregnancy loss will sometimes only be investigated after a woman has suffered multiple consecutive miscarriages.  

But there is hope. Breakthrough research could change the way women overcome pregnancy loss. Professors Jan Brosens and Siobhan Quenby are members of a team of experts in the U.K., Japan, and Singapore who are exploring the role that uterine natural killer (uNK) cells play in both facilitating and ending a pregnancy.

What Are Natural Killer Cells and Why Do We Have Them?

Similar to white blood cells, the natural killers are crucial to our immune system.

They help the body to fight tumors, viruses, and cancer cells. But there is a big difference between uNK cells and the NK cells that circulate in the bloodstream, since the former grow in large numbers solely inside the womb.

These cells clear and refresh the uterine lining in preparation for embryo implantation. And once this has taken place, they’re poised to attack anything that may interrupt the embryo’s healthy development. Fluctuating levels of uNK cells, however, are believed to disrupt this system.

How Do Uterine Natural Killer Cells Cause Miscarriage?

If the uNK cells are over or under-active, they cause an imbalance within the womb. Insufficient clearance of old cells means the embryo cannot implant, whereas overzealous clearing causes the uterine tissue to collapse. Professor Brosens explained: “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 can be short-lived or last for multiple cycles. Tests carried out by the team have revealed that women can have irregular numbers of uNK cells throughout the course of each month. Approximately 15 percent of women who experience recurrent miscarriage show evidence of cell fluctuation, while elevated levels of uNK cells could be behind as many as one third of unexplained miscarriages.

What Causes Elevated Levels of Uterine Natural Killer Cells?

Professor Quenby believes this could be indicative of another problem, such as low levels of the steroids necessary to manage both inflammation and the immune system. If inflammation is present in the body—especially as the result of existing autoimmune disorders such as hypothyroidism— this could cause the uNK cells to attack an embryo, believing it to be foreign body.

Steroid deficiency also reduces the formation of fats and vitamins that are essential for pregnancy nutrition, and therefore renders the womb less likely to accept or support an embryo. “We have excellent scientific justification for steroid-based treatment to prevent miscarriage,” Professor Quenby said.

A study was carried out in the UK where 160 women were screened for uNK cells. Those with less than five percent of the cells in their lining were considered “normal.” Those with more than five percent were considered prone to miscarriage. When 20 of these women took a steroid treatment, they saw a 60 percent success in live birth rate. When another 20 women took a placebo, they experienced a 40 percent chance of carrying their pregnancy to term.

But steroids can have major side effects on a woman and her unborn child. They reduce killer cell activity by suppressing the whole immune system, and leave a mother prone to infection. So is there another way to prevent miscarriage?   

How to Reduce the Risk of Miscarriage

Stress causes uNK cells to fluctuate, and the stress of trying to get pregnant after a miscarriage does not help, especially in women with sensitive immune systems. A solution to this, however, may lie in the timing. Professor Brosens believes there could be a window each month when the levels of uNK cells are considered “normal,” and the womb is therefore ready to host a baby.

A woman who has experienced multiple miscarriages may simply have conceived at times when inflammation was high and her womb not receptive, but this doesn’t mean it will never be receptive. Knowing that some women go on to carry a pregnancy to term, despite having had multiple miscarriages, can help to alleviate stress.  

Professor Brosens added: “We hope in the future this new information will be used to screen women at risk of reproductive failure. Furthermore, our findings suggest new treatment options for women suffering recurrent miscarriages or recurrent IVF failure.”

While screening methods are yet to be determined, know that options may be available to you. Knowledge of uNK cells promises to help all women by reducing the risk and heartbreak of miscarriage, even before pregnancy.  

Featured image by Evie Shaffer

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