What we can learn from menstrual blood

Does diet help with endometriosis? Can exercise help prevent repeated miscarriages? Renate van der Molen, Tess Meuleman, and Annemiek Nap (Radboud University medical center) seek answers to these questions by studying something that billions of women throw away every month: menstrual blood. “Menstrual blood contains all kinds of messages from the immune system.”

On the table lies an egg-cup-sized cup, made of flexible silicone, with a small spout at the bottom. “We use these cups to collect menstrual blood for diagnostics,” explains Renate van der Molen, Medical Immunologist at the Department of Laboratory Medicine. “Participants can easily collect samples at home. The blood goes into a test tube that contains a preservative fluid, until it is collected or sent to us by post. Women are increasingly using these cups anyway to collect their menstrual discharge. It’s a sustainable option because the cups can be rinsed with some water and vinegar, and reused.”

Renate started analysing menstrual blood at the medical immunology laboratory over a decade ago. “In the beginning, I encountered a lot of resistance. Some people found it dirty and weird. But menstrual blood contains a lot of information about the female reproductive organs, and it is available every month without having to stick a needle into a person’s body. The only extra step in the analysis is filtering the blood, because menstrual blood also contains a bit of mucus.”

From killer to babysitter

What makes menstrual blood so interesting is that in addition to blood and endometrium, it also contains all kinds of messages from the immune system. For example, it is full of immune cells and signalling substances. Renate: “We think that the immune system plays a major role in uterine disorders and pregnancy complications such as miscarriages. This makes menstrual blood an interesting diagnostic tool.”

This certainly applies to an important type of immune cells, the natural killer cells (NK cells). These cells are found throughout the body and normally protect the body against bacteria and viruses. They act like real killers, cleaning up any intruders. But in the womb, NK cells change their appearance and activities. They work to ensure that the mother does not reject the unborn child, which is partly foreign to the body because of the father’s input. NK cells also help further open up the blood vessels of the placenta, helping the nutrients to reach the embryo more easily. You could say that NK cells switch from killer to babysitter.

Repeated miscarriages

This means that unravelling the immune system and the tasks of NK cells can be interesting for women who suffer repeated miscarriages. “We don’t know much about what causes repeated miscarriages, and there isn’t much that doctors can do,” says gynaecologist Tess Meuleman of the Department of Gynaecology and Obstetrics. “In 50% to 70% of cases, we never find a cause. All we can do is offer what we call tender loving care, providing continuity of care with additional ultrasounds and attention.”

Tess believes that the immune system plays a crucial role in repeated miscarriages. A recent study conducted by Renate reveals that the menstrual blood of some of these women contains fewer NK cells than that of women who did not suffer miscarriages. “We think these cells play an important role in the implantation of the embryo and the creation of the placenta,” she explains. “We know from people with cancer that exercise boosts NK cells and improves survival. We therefore launched a study on the effect of exercise on repeated miscarriages.”

Sport and pregnancy

Tess hopes that exercise can also help boost the number of ‘babysitter’ NK cells in the womb, thereby increasing the number of successful pregnancies. In her study, women with unexplained repeated miscarriages first commit to exercising twice a week for six weeks. In the next stage, the female subjects exercise three times a week for six weeks. The study is open to women with high and low numbers of NK cells. Renate’s laboratory then takes all kinds of measurements, including the concentration of NK cells in menstrual and normal blood. Tess also uses a cycling test to check whether the women’s fitness has improved.

Ultimately, the study aims to lead to more successful pregnancies. Tess: “Miscarriages are still a bit of a taboo, but they cause much grief. Some women miscarry as many as 10 times. I would love to be able to help them.” She sees that these women are generally not really overweight, but they do tend to be couch potatoes. “They also tend to contract cardiovascular diseases later on. So exercising is a good idea for these women anyway.”

Endometriosis

Another example of a condition in which the immune system plays a major role is endometriosis. “Endometriosis involves inflammatory reactions caused by tissue similar to endometrium but located outside the uterine cavity. And this causes pain,” explains gynaecologist and head of the Department of Gynaecology and Obstetrics Annemiek Nap. Endometriosis has received a lot of attention in recent years, leading to greater awareness around it. This is important, as the condition affects one in ten women of child-bearing age.

“We can treat endometriosis with painkillers, hormonal drugs, or surgery, but treatment is not always successful,” says Annemiek. “In addition, women find it important to be able to do something about it themselves. Many women say that a diet helps. They experience positive effects from a variety of different, sometimes even contradictory diets. We therefore think this success is partly due to the placebo effect. Still, an anti-inflammatory diet can really help. We want to investigate whether we can use nutrition to reduce inflammation.”

Anti-inflammatory diet

To this end, Annemiek initiated a study with a specially developed anti-inflammatory diet. Annemiek: “Our diet contains a lot of vegetables, fruits, nuts, and pulses. It’s also low in sugar and saturated fat. This diet contains everything a person needs, and women can follow it for a long time. This is usually not the case with diets that are recommended on the internet, which often end up leading to deficiencies. Our diet constitutes a healthy and sustainable lifestyle change.”

Annemiek collects measurements of immune cells in blood, menstrual blood, and vaginal fluid from the study participants. She does so first before the women start on the diet, to create a clear baseline, then again after three months on the modified diet. In this way, women constitute their own control group in this study, and there is no need for a separate control group that is not on the diet. “We hope to be able to show that a well-balanced diet reduces inflammation and other symptoms of endometriosis.”

Future

The researchers are therefore using menstrual blood analysis in two clinical trials at the Radboud university medical center. Renate: “I'm glad that we get a chance to demonstrate the value of this technique. People are not always eager to work with menstrual blood; this applies to doctors and lab technicians, but also to our test subjects. But this technique does provide us with a wealth of information about the uterus, and I expect it to play a far greater role in the future.”

More information or participate?

Repeated miscarriges: www.hmovestudie.nl.  
Endometriosis: please contact emma.huijs@radboudumc.nl

This article was written for Radbode #8, 2022.

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