Hyperemesis Gravidarum researcher Dr. Marlena Fejzo is on a mission to understand women's health

Liz speaks with geneticist and hyperemesis gravidarum researcher Dr. Marlena Fejzo about her groundbreaking work on the condition that impacts six million women globally during pregnancy and is characterized by severe nausea, vomiting, weight loss, dehydration, and in severe cases, death. Dr. Fejzo also talks about her own tragic experience with HG and shares her thoughts on why she believes there is still so little research on women's health concerns.

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Liz Tenety: I am Liz Tenety and I want to welcome you to The Motherly Podcast.

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Liz Tenety: So, as regular podcast listeners might know, I have four children and with three of those pregnancies, I experienced a condition called hyperemesis gravidarum, HG, which is horrible morning sickness. It's debilitating. It's just simply put like the hardest thing that I've ever gone through in my entire life.

And it's terrifying. I really never want to go through it again. For me, thankfully, it tends to let up around 20 weeks, but the first part of my pregnancy is unbelievably hard. I cannot get out of bed. I am vomiting constantly, even on medication. I can't do anything. I can't take care of my kids. I can barely work and I've had it with my first, my third and my fourth children.

Having HG is part of my story and it is one that has been incredibly humbling and scary, and almost every woman I know who has had a baby has some really hard thing that she's gone through, whether it's secondary infertility or HG or a genetic condition that gets diagnosed when she's pregnant. Finding out her baby is breech, having an unexpected C-section, postpartum depression… We go through incredible hardships to bring babies into the world. And I don't think we talk about that enough. I don't think women get enough credit for being the heroes, the heroines that they are to endure this, to bring the next generation.

Liz Tenety: Hey mama. Welcome to the motherly podcast, honest conversations about modern motherhood. My name is Liz Tenety. I am the Co-founder of Motherly and I'm a mom of four myself. Today's interview is with Dr. Marlena Fejzo, a geneticist and the leading researcher on hyperemesis gravidarum. HG, as it's called for short, affects about 6 million women globally each year during pregnancy.

And it's characterized by severe nausea, vomiting, weight loss, dehydration, even sometimes organ failure. And in severe cases, it can lead to the death of mothers and babies. After experiencing HG herself and losing her baby to the condition Dr. Fejzo decided to devote her life to studying it. She's discovered two genes associated with hyperemesis gravidarum that has helped to shed a light on this little understood illness. In fact, her work has really changed the paradigm about what causes HG and this really debilitating condition for pregnant women. I actually experienced HG in three of my four pregnancies. So, I am so grateful for Dr. Fejzo's work.

Currently, Dr. Fejzo is a science advisor for the Hyperemesis Education and Fesearch Foundation called the HER Foundation for short. And that's the global voice for HG awareness research and support. Today it receives 200,000 visitors each year from around the world and they manage a global volunteer network with over 900 participants, all built to help women suffering from HG, find the resources and support they need.

I talked to Dr. Fejzo about her own experience with HG and how going through HG as a geneticist inspired her to do this kind of research and really lead the charge on understanding what the actual underlying causes of this debilitating condition. And we also talked about funding of women's health and how there is so little still understood about pregnancy and the changes that women go through biologically through their lives.

There are a lot of reasons why women's health has been historically underfunded and we get into it. Her work is incredible. I'm excited to share this conversation with you.

Dr. Marlena Fejzo, welcome to The Motherly Podcast.

Dr. Marlena Fejzo: Thank you for having me.

Liz Tenety: So, I know we just met, but you are one of my favorite people on the planet. I have been diving into your incredible research, your work on hyperemesis gravidarum known as HG and as a woman who has suffered from HG three times, like I cannot get enough of learning about what you are discovering.

And I can't wait to talk about all of that. So, can you actually define what hyperemesis gravidarum is and what are the symptoms that women should be looking out for?

Dr. Marlena Fejzo: So, hyperemesis gravidarum is nausea and vomiting. That's severe enough to affect your daily routine and to affect your intake so that you're not able to eat or drink properly. And that leads to weight loss. Usually it's diagnosed when you have more than 5% of body weight loss and electrolyte disturbances for not being able to drink or eat properly.

Liz Tenety: So, can you tell our listeners a bit about your own personal story and why you decided to devote your life to not only studying HG, but a lot of critical topics in women's health?

Dr. Marlena Fejzo: I did my PhD in genetics and women's health. My PhD was from Harvard on uterine fibroid tumors, which are also a big problem for women. And, you know, there's not as many female scientists as male scientists. And so, for me, it was very important to focus on women's problems. You know, there's plenty of scientists working on male problems and not very many working on female problems.

And then I went on then I had HG during my post-doc and then had it again. In my second pregnancy, I had a really, really, very severe HG pregnancy. My second pregnancy, the baby died in the second trimester because I was so ill. I didn't keep anything down for 10 weeks and I couldn't move without vomiting. I got so weak. I couldn't speak. I had to have a buzzer to signal when I needed a bed pan change or a medication change. I basically could not move for weeks and weeks. And finally, the baby died. And I decided to look into what was known about HG and there was so little known that I decided, I'm a scientist and I've got to devote my life to figuring this out.

Liz Tenety: There's so much you've already said that is so powerful. And I know our listeners can't see us, but I'm tearing up hearing it because there aren't words to describe what you go through with HG. That was part of this conversation as I was imagining it, I can't tell you what it's like to go through that, but you described in your particular case, you literally could not move your body. It was the most dark time of my life to go through those three pregnancies.

And yet, you have led a body of research into the evidence of what is actually happening inside women's bodies. When they experience HG, what was believed about the cause of HG before, you know, there was this new wave of research and understanding.

Dr. Marlena Fejzo: Yeah. So, that's the terrible thing, since it's a women's problem. And on top of that, a women's problem during pregnancy, and there's sort of always, you know, you see it still in the movies and on TV that there's this idea that pregnant women are hysterical or irrational. And so, that perpetuates this idea that it was all in a woman's head and over time, there were theories that really got picked up that it was a subconscious rejection of their pregnancy that they didn't want to be pregnant and all kinds of irrational theories that are just not scientific and not true.

Liz Tenety: So, what is the difference between morning sickness as we know it and what do we believe morning sickness… like what is the purpose of morning sickness and what is the difference between that and HG?

Dr. Marlena Fejzo: No one really knows for sure, but we can guess that morning sickness has evolved as a way to avoid foodst hat would be dangerous. When the fetus is developing, when all the organs are developing and you don't want to ingest anything that could affect that.

And so, what comes with morning sickness is this increased sense of smell and taste. And so, those are generally thought as a way that has evolved to protect the fetus. With HG, it's just morning sickness out of control.

Liz Tenety: I kind of had heard from my doctor when I first had HG with my first child, she seemed to think it was in my stomach, that the problem was happening in my stomach. And it was about eating crackers and always having something in my belly. These were the ideas that I was being told to start to remedy it. But your research is showing that it's actually happening in the brain, or it's at least this cycle of feedback that is neurological.

Dr. Marlena Fejzo: Exactly. So, since I'm a geneticist, I decided to look first into seeing whether it was genetic. I don't have it in my family, but I decided to look into it. And what I found was that. There was a lot of evidence that it's genetic, there's a 17-fold, increased risk of having it if your sister has it. And twin studies where they compare the genes and the chance of getting hyperemesis in identical twins versus fraternal twins have shown that it is highly heritable.

So, there's a lot of evidence that it's genetic. There's 70% heritability. What I then did was to embark on a genetic study and I partnered with the personal genetics company, 23andme and we scanned over 15 million genetic variance in over 50,000 women that did not have HG compared to 1300 women that were hospitalized with HG.

And so, we compare their DNA at these variants and we found very significant differences in their DNA around this hormone called GDF 15. And that hormone is turned on in the placenta. It's expressed very highly in pregnancy. A lot of doctors thought that it was caused by a pregnancy hormone, if they didn't believe the psychological theory, but we found no evidence to support GDF 15 as being the causal hormone. We found very strong evidence for it being this hormone, GDF 15.

Then I went on to see, okay, so it's genetically associated, but what about the actual hormone itself and confirmed that there are significantly higher levels of this hormone in the blood in women with HG compared to women without HG. And then, recently the receptor for this hormone was found by other groups and the receptor, which is what the hormone binds in the brain that causes this nausea and vomiting and loss of appetite and change in taste, it goes up travels through the bloodstream. It goes into the brain, binds this receptor, and then causes this nausea and vomiting. And that can get out of control because if you already have this predisposition to have higher levels, you're going to vomit more than normal. You're going to have nutrient deficiencies, which lead to another further increase in the levels of GDF 15 and you get this downward spiral to hyperemesis gravidarum.

Liz Tenety: And those nutritional deficiencies that mothers get when they have HG, lead to, you know, negative impacts on the fetus, including much higher rates of autism.

Dr. Marlena Fejzo: Yeah. So, there is, I wouldn't say much higher… I don't want to scare women, but there is an increased risk for neurodevelopmental delay.

There's an increased risk for autism, you know, speech, delay, language disorders, different kinds of neurodevelopmental disorders. And, you know, long-term outcomes in the mother, as well as the child. So, it used to always be thought that, you know, don't worry about what you get. The baby's getting everything it needs from mom, but in the case of HG, that is just not true.

Liz Tenety: That is literally what my doctor told me. And that child, that first pregnancy we have had diagnoses along those lines. So, you know, I can't say for sure, but I am living your research every day. I wonder when you're doing your work, you brought up how women's health and maternal health for a number of reasons has not been as much of a focus of the scientific community as the health and wellness of men.

Do you feel excited about being a pioneer in this field, or do you feel frustrated that we've had women as long as we've had human beings and we still don't know some of the basic things of how our bodies work, because we haven't invested in this kind of research?

Dr. Marlena Fejzo: That's a good question. I would say I have days of both there's days where I'm really excited and so happy that we're making progress, but the progress is so slow. We need other people following my path. The fact that I am a world-renowned researcher in this field is not really because I'm so great. It's because there's barely anybody else. It does definitely bother me that there's so little research out there and that it's going so slowly and that, you know, I still hear stories of women being mistreated with this disease.

And I've been out there publishing for 20 years to try to change that. So, I definitely do feel frustration often, but yes, I'm very excited that we finally made some progress and hopefully we can change things. And a lot of people don't know about my research. And so, it's really important to get the word out and spread the word

Liz Tenety: As a result of your research, finding that there is DNA in certain women, that you will have particular genetics that lead to this cycle, and you have HG—it will lead to a different kind of treatment. Is that right? Where are you in that process of now that we understand HG, what do we do about it?

Dr. Marlena Fejzo: Yeah. So, it's a pretty new finding and the fact that this is a hormone and the identification of the receptor for it are pretty new. So, we have a ways to go to understand how this all works, but we are hopeful that there will be medications that will be used to block this pathway so that we can actually have something that works to treat HG. The interesting thing about this hormone is that it also is involved in cancer.

Cachexia is basically when you can no longer eat, when you have cancer. And it kills about 20% of cancer patients. And just like GDF 15 is overexpressed by the placenta, it's also overexpressed in some cancers. And so, those patients that have high levels of GDF 15 turned on in their cancers also have this appetite loss muscle wasting and they ended up many of them dying from it.

When women say they feel like they're dying from HG, often people do not believe them. They say they're exaggerating. But the actual levels of GDF 15 in women that are pregnant and have HG is the same, or sometimes even higher than people that are dying from cachexia.

Liz Tenety: I'm getting choked up again because that's what it feels like. But I think people may not realize too, when you have HG, it doesn't just affect you when you're pregnant. I mean, it affects, of course, the experience. But many women decide to terminate these wanted pregnancies because they cannot endure what they're going through. Some women have PTSD. And even though it's a small segment of women, it is very traumatic and some very prominent women, Amy Schumer, Kate Middleton have gone through it. But like you said, we're just starting to wrap our heads around how overwhelming and how misunderstood this condition has been.

Dr. Marlena Fejzo: Yes, it is overwhelming, misunderstood, and it has long-term effects for the mom and it can have long-term effects for the child.

Liz Tenety: There are other considerations when it comes to reasons why this kind of research hasn't has not happened. One of them is that there was a medication in the 20th century that negatively affected a lot of women and children. There are other ethical considerations with pregnancy. So, how do you navigate that in your own research and understanding.

Dr. Marlena Fejzo: Yeah. So, there was a drug that was given in the fifties to women for HG in Europe. And it ended up causing birth defects, limb deformities. And so, unfortunately, that has caused pharmaceutical companies and doctors and patients themselves to be scared to develop, to treat patients and to take medications in pregnancy.

I think that the tide is starting to change. With that, as you know, we're starting to understand that some medications can be safe in pregnancy and, you know, we have to go slowly to make sure that I don't know if a GDF 15 inhibitor is going to be safe in pregnancy, but we're going to have to try.

And the fact that there can be long-term outcomes to the child if they don't take medication, has to be weighed against the possible risks.

Liz Tenety: Thrilled to hear that the tide is turning. If a woman is experiencing this and she's going to go to her doctor or her midwife, and just say, I am, I'm just so sick. How does she know how to flag that this is not normal morning sickness? That this is a severe condition that requires a different level of intervention.

Dr. Marlena Fejzo: Exactly. So that's why we developed our HG care app so that women could know, because especially in their first pregnancy, a lot of women don't know, and they haven't seen a doctor yet when the symptoms start.

And so, they can be missed before it's too late. There was actually a woman that died just in August. She was only nine weeks pregnant, so it's very important for women to know what the symptoms are and what is normal. And I feel like every woman should be screened immediately when they're first pregnant for this, because right now, a lot of women only go to the doctor and have had their first appointment pretty late after symptoms of HG can already get severe.

So, our app has alerts to tell you when you need to talk to your doctor, but generally if you're getting dehydrated, then it's time to see your doctor. If you're not able to eat, if you're not able to drink, you're not able to do your normal daily routine and you're losing weight, you're actively losing weight. Then you need to talk to your doctor about possibly having HG. There is a test where you can pull up your skin on the back of your hand, and normally it should bounce right back. If it goes back slowly, then that means you're dehydrated. And you need to get hydrated.

Liz Tenety: I want to talk a bit about the foundation. Can you tell me about it?

Dr. Marlena Fejzo: So, basically the way it happened was after my HG nightmare, I realized there was so little known and I put out a survey with my brother. He helped me. He's a statistician. And we put out a survey on the internet about HG and put in questions about it that I wanted to know the answers to. And one of the women that answered that survey faxed back her answers and that was Kimber McGiven and she was a nurse who was going through HG and she said, I'm so sick now, but I was so happy to find your survey. She wrote on her survey, as soon as I'm done with this pregnancy, I'm going to make a website. And so, she made a website on HG and she's amazing.

She's been working for years on this, only recently giving her itself a tiny salary, but she's just devoted all her time with no pay to do this. And she has an amazing website. And then she got joined by another couple that had gone through a horrible HG pregnancy and they then created the foundation: The HER Foundation. And so the webpage is hyperemesis.org and I'm a science advisor for them. And I'm on the board.

Liz Tenety: What is the current best evidence-based treatment for HG? And what can those around a woman going through HG do, if anything, to relieve any of her suffering?

Dr. Marlena Fejzo: So, we did research on what women found to be the most effective treatment. So, I'm basing my answer on that, which is that on Dantron or Zofran was the most effective treatment for women in our study for helping to lessen the, the vomiting. It doesn't necessarily help that much with the nausea in all women, but it does lessen the vomiting in more women than any other medication reported except for possibly steroids.

But doctors often do not give steroids to women because there are some possible safety concerns. So, that's from our study. But unfortunately, even on Zofran, it's reportedly only effective in maybe 50% of women. So, we definitely still need something better.

To answer your second question, what can we tell the families, women with HG need a lot of support? They need an advocate. When you're feeling nauseous, you cannot advocate for yourself. So, they need someone to go with them. To doctor's appointments and and to speak for how ill they are. When a woman is ill and feeling like they're about to throw up, they're not going to speak out to their doctor when their doctor says something that they don't agree with.

Like, oh, just take crackers. So, women need to have either a family member or friend go to the doctor and explain.

Liz Tenety: And yet, like you said, I mean, I literally heard from my doctors, the baby's a parasite and the baby will take everything that the baby needs, but your research has shown that that's just, that's just not true.

Why is it that there's so much conventional wisdom that isn't evidence-based that is still out there in modern medicine, especially as a relates to women?

Dr. Marlena Fejzo: I think it's really hard to get the word out and that these ideas are passed on then medical books and the medical schools. They're teaching the next generation of doctors, the same things that they learned and not updating it.

So, I've heard of this year, a doctor teaching her medical students. (One of them had HG. So, she's the one who told us about this.) She was teaching her medical students, that women, they're sometimes hospitalized, and they just don't want to get better. That's what she told this next generation of doctors in a class. Women just don't want to get better.

This was a female doctor teacher teaching her next generation of students. So, if they're learning that from someone that they trust to teach them the facts, then that's what's happening. And so somehow that has to change and we have to just get the word out the best we can.

Liz Tenety: What are the other big topics in women's health and maternal health that we don't know enough about?

Dr. Marlena Fejzo: There's menopause, lupus that occurs more in women, many, many women's issues. And just having your period and the medications to help with cramps, you know.

Liz Tenety: Well, it seems like being a woman is the qualifying factor, because if its periods to menopause, that covers a lot of our lives that we may not know as much about as we should.

Dr. Marlena Fejzo: One thing you asked me before about, you know, am I excited or am I… I don't mean to be only negative because we are making progress and things are slowly changing. But one of the things that I was really upset about that really got me riled up was that the national Institute of health funded a genome-wide association study, which is the same type of study that I did with 23andMe, because I couldn't get funding from the NIH.

They funded a study on erectile dysfunction. Erectile dysfunction, first of all, is not nearly as heritable. There's not as much genetic evidence to support that it is genetic compared to hyperemesis and other women's issues.

And yet they funded that. In addition, with erectile dysfunction, there are millions of dollars, billions of dollars spent on it by drug companies by the government. That was really frustrating to me. Erectile dysfunction is bad too, but when you compare it to HG, that's affecting the mother and the child. I don't think you can compare it. And so, it's just an example of money being spent on male issues and not female issues.

Liz Tenety: After you lost your baby at 15 weeks through that experience you had with HG, you did go on to have other children. How did you navigate the decision to have more children? And I know you ended up working with a surrogate. So, what was that like? Tell us about that.

Dr. Marlena Fejzo: Yeah, so having a surrogate was never something that was on my radar, especially back then. There were very few people that did that.

Liz Tenety: What year was that?

Dr. Marlena Fejzo: That was back in 1999. It was something that my OB suggested to me that I was a good candidate for. And after I lost the baby, you know, I had one child and I come from a big family. I have two brothers and a sister, and I always wanted a big family too. So, it was going to be either surrogacy or adoption for me. I was not going to go through HG again.

Liz Tenety: Do you see those experiences as different motherhood's or is there a theme in how you've bonded with those children in the same way or in a different way? How do you see that?

Dr. Marlena Fejzo: I think it was the same as far as, you know, giving birth and having the surrogate. I was able to watch her give birth to my babies, and I really consider her my angel for doing that for me. And both ways are miracles, you know, giving birth to a child is a miracle, but having someone else do that for you is also such an amazing miracle.

Liz Tenety: Do you feel that the loss of your child that you did experience is a source of motivation or meaning in your ongoing research and advocacy for HG?

Dr. Marlena Fejzo: Definitely. I mean, that is what keeps me going. I don't want that to happen to anybody else. I know it's still happening to women and it's very sad for me when I, you know, women write me and tell me they've gone through that. It's very sad and frustrating to me because I've been working on this for 20 years and to see that women are still going through this and I hope that it's going to change. And I hope that we're going to find a medication that works and stops that. But yeah, definitely. And I don't want to see my daughters go through it either, of course. So, that will be devastating to me if they have to go through that.

Liz Tenety: Okay. So, at Motherly, we believe that motherhood brings out our superpowers and to me, a superpower is something unique, a strength perhaps within you that maybe you didn't even know was there before you became a mom. So, I wonder what you think is your superpower.

Dr. Marlena Fejzo: Patience. I would say patience is really important as a mother and as a scientist. Patience and trudging slowly on. There have been many, many setbacks in my research and just getting up and go forward again. Being patient. We're getting there. But yeah, with kids too. You need patience.

Liz Tenety: I love that. Well, Dr. Marlena Fejzo, thank you so much for sharing your story and your research with baths on The Motherly Podcast.

Dr. Marlena Fejzo: Thank you for having me.

Liz Tenety: Now for a quick word, from this episode's sponsor ThirdLove. Motherhood is one of the most amazing and transformational experiences a woman can have. It's about feeling the joy of bringing this new little person into the worlds and learning how to be comfortable in our own skin, finding a new routine and owning our new confidence.

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Liz Tenety: When I'm pregnant, do you remember what happens to me at the beginning of most of my pregnancies? What happens when I get really sick?

Henry: You start to throwing up like three times, each day, three to 10 times each day.

Liz Tenety: Yeah. It's like 10 to 15 times a day. Yes, you're totally right. If you remember, I just basically stayed in bed for three months. Do you remember that part?

Grant: How'd you eat?

Liz Tenety: I couldn't eat

Grant: But then you wouldn't be able to survive.

Liz Tenety: I just get the tiniest amounts of food and water. And sometimes they put the IVs in my arms to get me fluid. But you know, I was like that with you, Henry. But with Grant, I didn't get really sick, but so with three of the kids pregnancies, I got super, super sick, but one kid and I'm looking at him, he did not make me throw up 10 times a day. Good job, Grant!

Grant: Because I'm so disgusting.

Liz Tenety: Oh, is that it? Because you are so disgusting, that's why I didn't throw up?

Grant: Hmmhmmm.

Liz Tenety: Well, that's it for our show this week. I can't thank you enough, Dr. Fejzo for your time and for your work.

And I also want to thank our listeners for listening to our podcast. This season, we have an incredible lineup coming in 2021. I can't wait for you to listen. And as always, we would love it if you spread the word about The Motherly Podcast.

So, if you can leave us a review on Apple podcasts, it takes 30 seconds max, and it really helps other mamas discover our show.

The Motherly Podcast is produced by Jennifer Bassett with editing from Seaplane Armada. Our music is from the blue dot sessions and I am your host, Liz Tenety. Thank you so much for listening.

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