Current Research on Endometriosis: An Interview with Prof. Vivian Yang

“We just want women to become alert and recognize if they have this problem. That’s all.”

Dr. med. Nadine Rohloff: Hi, I’m very happy to be here with Professor Vivian Yang from Taiwan in our series of interesting research on endometriosis that we started since the World Endometriosis Congress. I’m very excited to speak to you and I think it would be great to start with you introducing yourself. Tell us a bit about yourself.

Prof. Vivian Yang: Thank you. My name is Vivian Yang. I’m currently a professor at Taipei Medical University. We have a startup company that mainly focuses on identifying novel biomarkers for early detection of women’s diseases. I’m very happy to be here to share our experiences in Taiwan about endometriosis.

Dr. med. Nadine Rohloff: I always find it interesting to hear how research is done in the field of endometriosis because sometimes you don’t hear about it in the clinics. We want to show that there are a lot of interesting things happening. You’re focused on biomarkers, but also on gynecology and endometriosis. What brought you to the topic of endometriosis? Why did you end up here?

Prof. Vivian Yang: When I started my academic career at Taipei Medical University, the first department that I worked with was all professors in research. That is a multidisciplinary field that can bring our discoveries from basic science to the application in the clinic. That’s why I visited the Department of OB-GYN [Editor’s Note: Obstetrics and Gynecology] and joined their daily morning meeting. I found out that there is a disease called endometriosis, which has a cancer-like behavior but is benign. As a biochemist, I was thinking: How come there are already many diseases that have biomarkers for early detection? Why do we still not have biomarkers for the early detection of endometriosis? The first idea that came into my mind was that it is commonly looked at in people’s blood to ensure they are in good health. If we can find any serum markers that could be related to endometriosis, then maybe we can identify useful biomarkers for endometriosis. That’s how I started my research.

Another thing is that I found many are suffering from menstrual pain without knowing they have endometriosis until they have fertility problems. Later on, I found out that a significant percentage of women suffering from endometriosis may further develop infertility problems and even have worse endometriosis-associated ovarian cancer. That made me start to have this idea that we do need to use our expertise to try and find good biomarkers. We also provide a convenient test, because my friends and I are all working women and we are very busy. We don’t want to have a very complicated check for our health.

I have some friends and some students from Indonesia. They told me they did not want to walk into clinics because some religions hesitate to see a doctor. I think it’s important to have blood or urine tests for in-vitro diagnostic tests because endometriosis can come back very often, even after receiving treatment. We need to do a follow-up. That’s why we started looking for biomarkers and trying to develop a convenient, reliable, and affordable test for women.

About Prof. Vivian Yang

Vivian Yang is a Professor at the Taipei Medical University in Taiwan. She also runs a start-up company and focuses mainly on identifying biomarkers that can be used to develop an easy and cheap test for endometriosis. She is optimistic that they can research and develop an affordable test for women potentially affected by endometriosis.

Dr. med. Nadine Rohloff: That’s very important. It sounds like the problems with endometriosis in Taiwan are very similar to the problems we have in Germany: the late diagnosis. When we have a late diagnosis, we have complications and more chronic diseases. How would you say is the endometriosis care in Taiwan? What are the problems there?

Prof. Vivian Yang: In Taiwan, many women do not realize they have endometriosis. Usually, even if they have menstrual pain every month, they just take painkillers and then stay home for a couple of days until the symptoms go away. They don’t really realize they have the disease until they want to have a baby. That’s exactly what happens in our clinic. Based on our data from Taipei Medical University Hospital, the Center of Reproductive Medicine, almost 50 percent of women in the infertility department have endometriosis. That’s very high.

As you may know, Taiwan is probably the top or the second-lowest birth rate in the world. Women are getting married at a very late age. Our average marriage age in Taiwan is about 32 years old. Women have their first baby very late. If we look at the record and the reports around the world, the delay in diagnosis for endometriosis is six to eight years. This means probably a girl around 20 or 25 years old has already started to develop the disease. If we could help girls or women realize that they might have this disease, then maybe we can get better control and delay the further progression. They may still have a higher chance of getting pregnant naturally. In Taiwan, we also have a lot of women who try to use artificial reproductive technology. They walk into an IVF center if they want to have a baby. If the uterine environment is not healthy, maybe the women can still not receive IVF to have the baby. I think that’s another problem. We just try to help and stay on the patient’s side.

Dr. med. Nadine Rohloff: That brings us to your research. Maybe you can start with what biomarkers you are looking at and why.

Prof. Vivian Yang: As I mentioned, we started from blood tests, because they are very common and everyone accepts them. Except maybe for patients who are scared of needles. We did find a lot of biomarkers, like cytokines, that already had many papers published on them and might be related to endometriosis, because it is a chronic inflammatory disease. We do see a lot of inflammation-related molecules present in the blood that signals associated with endometriosis. Again, because it is inflammation-related, someone has a cold and might also have those signals in the blood. How can we distinguish between endometriosis and the other inflammatory condition? We took many years trying to distinguish that by looking at protein in serum.

We see the signal, but it is difficult to develop a test because some proteins are only expressed in a typical high window. We also consider that we want to develop a very stable and convenient test for people to walk in, give blood, and have the test results. We ended up finding this protein, which is called Alpha-1 antitrypsin. It is also an inflammation-related protein, but we found that there are many isoforms of this protein, and only some of the isoforms, called iso-AAT, are related to endometriosis. We think it is a very interesting molecule. These molecules are stable and also have a measurable amount. We think that could be developed as a convenient test, so we don’t need to develop a special testing platform. Because then they may need a specialist to get familiar with a new test. We just found this biomarker and we can integrate it into a very common testing platform called ELISA [Editor’s Note: Enzyme-linked immune-absorbent assay]. That will be easier for everyone, not only for the patient side but also for the lab specialist to handle this kind of test.

Dr. med. Nadine Rohloff: It’s a test for which the laboratory already has the machines and just needs to adjust the test. That’s very cool. This protein, you say, is related to endometriosis, and it’s inflammatory. Can you tell us more about the protein and which connection it stands for? How does it behave in endometriosis?

Prof. Vivian Yang: These iso-AAT biomarkers have significantly increased expression in blood when we see patients with endometriosis compared to patients without endometriosis. This is what we found. We kept validating it by collecting more samples and trying to confirm whether it was true or not. Secondly, in this protein, there are almost 20 different isoforms, but we only found that two or three isoforms are related to endometriosis. In the next step, we tried to develop antibodies that specifically recognize these endometriosis-associated isoforms.

Then, we would integrate them into the ELISA platform, because that is simple. This is what our research is doing most of the time. What we did was to try and validate it because there are so many different subtypes of endometriosis. Plus, there are comorbidities. I mean, women who have endometriosis may also have other problems. How can we distinguish that? We also spent some time trying to confirm and validate if this biomarker is specific to endometriosis. That’s how we do the research and try to develop by using this marker to develop antibodies for the test.

Dr. med. Nadine Rohloff: That’s very interesting. I think an interesting question in endometriosis is also how the biomarkers behave with recurrence. When we operate endometriosis – how does it behave afterward? Is that something that you have planned as research, or is it something that you have already done?

Prof. Vivian Yang: Thank you. This is a very good question. Very interesting. Yes, we also need to consider recurrence because we found that, based on the report, in 30 to 40 percent of women, even if they receive laparoscopy, the disease would reoccur within a year. Another thing is even when women do not receive surgery, they may take some hormone treatment. If they stop the hormone treatment for some reason, for example, because if a woman receives hormone treatment, she cannot get pregnant, the disease may reoccur. That’s the first thing we are trying to solve. If we want to look at whether iso-AAT could be reduced after receiving the treatment, then the level will start to increase if the disease reoccurs. We have already done the first rounds to confirm that with Gonadotropin-releasing hormone agonists [Editor’s Note: a drug that causes a reduction in estrogen and androgen synthesis that can be used to reduce endometriosis-related symptoms (Surrey, 2023)]. Lupron is a common medicine that is being used in Taiwan for endometriosis. We found out that if women receive this kind of hormone drug one month later, the iso-AAT level will decrease. If they stop, we have to initiate another round of a clinical trial to see if the disease reoccurs. Will this iso-AAT be increased then?

In the previous rounds of clinical trials, we did not typically look at that condition because it also takes time to follow up. We think that medical treatment would be a way to treat endometriosis, especially for women who may not have severe symptoms but just want to reduce the pain symptoms. They may take hormone drugs. There are more choices now. We just initiated a clinical trial to follow patients who take a different kind of hormone drug. What is the correlation between the iso-AAT level and the patient after they receive this different kind of hormone drug?

Dr. med. Nadine Rohloff: I think that’s very interesting. First of all, it’s important for the people listening to really understand this is a step-by-step process. You can’t look at 10,000 things in a study because you must have a valid statistical analysis. It’s important to know the step-by-step process. It’s really great that you’re looking at all those different treatment options. I think it’s also very great that you look at the symptoms. It’s important to know how this biomarker correlates to the activity of the disease, maybe what you see in laparoscopy. This is often what is done in the first place. What do we see? What do we see in the biomarker? From a clinical perspective, it’s so important to see what happens when you take hormones. What happens in correlation to how the woman feels? It’s important to interpret the biomarker, then.

Speaking of biomarkers and diagnostic tests, we have a lot of women who suffer from endometriosis or who think they might suffer from endometriosis. Of course, one of the first questions that they have is, how long does it take for it to be validated? Can you give us an outline of what your plans are?

Prof. Vivian Yang: When I presented just two weeks ago at the World Congress for Endometriosis, at the end of my presentation, I said this is just the beginning. We are looking to collaborate with medical doctors, hospitals, and labs to validate this biomarker because all the data we collect is from Taiwan. Therefore, we think it is important to continue to collect data. Definitely, we will try to push and try to collaborate with medical doctors in Germany and other countries to validate this biomarker and make sure that these tests are really useful. We will try our best.

We also need to consider the regulations because different countries may have their own regulations. Of course, if you have an interest, then you can participate in the clinical trial. That won’t affect you a lot. You just give one or two tubes of blood and then you can get results. That may be the fastest way to access and then have this testing. However, that is for research about the clinical data. First, we need to collect more data. Secondly, we will try our best to launch this test on the market. One thing I’m very sure of is that it won’t cost a lot. We don’t provide a very high-cost test. We just give a reliable and convenient test for women. But this is just a test, we cannot do any treatment. All the treatment needs to be administered in a clinic by medical doctors. We just want women to become alert and recognize if they have this problem. That’s all.

Dr. med. Nadine Rohloff: That’s great. We will make contact if somebody is listening or seeing this and wants to contact you. For all the people who suffer from endometriosis who hear this, I think the best thing you can do to speed up the research is to participate in studies [Editor’s note: i.e., https://www.endofound.org/research-opportunities]. We have a lot of women who participate in studies and that is a good way to push things forward because you need funding but you also need participants, otherwise, it takes a long time. That’s one important thing. For clinics that listen to research on biomarkers, this is very important. It will bring endometriosis as well as the treatment further so that we can help a lot of women faster, better, and earlier. That is a nice conclusion to our interview.

Thank you, Professor Yang, for all your work in researching endometriosis. I think a lot of women out there appreciate it very much, that you dedicate your work to this problem. Thank you for spending the time with us to tell us about it. People know that there are actually things happening and we’re going in the right direction, step by step.

Dr. med. Nadine Rohloff
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