A Cure For HG Is Coming

Hyperemis gravidarum, or HG, is a debilitating pregnancy nausea that affects 2% of pregnancies. Researchers know how to cure it — if they could only get funding.

by Rae Nudson

When Olivia Myers became pregnant with her first child, she was so nauseated that she had to either miss work or work from home in Calera, Alabama, from bed, with a trash can nearby. With her doctor, she attempted to ease the nausea and vomiting. She tried an anti-nausea medication, and then another and another — more than 10 different medications in all. A nurse came to her home to administer IVs to help with the dehydration from vomiting. She would walk around with a needle in her arm, wheeling around a pole that held the fluid slowly flowing into her body. She tried a Zofran pump — an anti-nausea medication that entered her body through a small needle she wore on her skin and a pump that she carried around in a backpack.

“It wasn’t working,” she says.

At her lowest point, when she was about 12 weeks pregnant and bedridden due to nausea and vomiting, she became terrified she wouldn’t be able to remain pregnant. “I was so scared that I was either going to miscarry or that I just wasn’t going to be able to do this for nine months,” she says. “I was having a mental breakdown.” Her husband considered taking her to the hospital on her worst day, a day she vomited 12 times.

Although most people experience some pregnancy nausea, an unlucky group that Myers belongs to experiences such severe nausea that can have serious effects on their bodies and lives. Myers had hyperemesis gravidarum, often known abbreviated as HG — severe pregnancy nausea characterized by a disruption in regular life, the inability to eat or drink regularly, weight loss, and sometimes malnutrition. It can become so severe that it can lead to miscarriage, organ damage, or death. About 0.3% to 2% of pregnancies are estimated to have severe HG. But pregnancy nausea and HG are on a spectrum, and even mild HG can be miserable.

Marlena Fejzo, a geneticist at the University of Southern California, was one of those unlucky 2%. Fejzo had HG in two pregnancies. Her first pregnancy, in 1996, left her with nausea and vomiting so severe she couldn’t work for two months and she received IV treatments twice, The New York Times reported. In her second pregnancy in 1999, she became so malnourished from severe nausea and vomiting that she was put on a feeding tube. “I didn’t eat or drink for over a month,” she tells me. She miscarried at 15 weeks. When she came back to work after the loss, she told her boss she wanted to find the cause of HG. Her boss, the chair of the genetics department at the University of California, Los Angeles, laughed at her.

So for the next two decades, Fejzo researched HG in her free time, when she wasn’t researching ovarian cancer. “There was sort of a ‘don’t ask, don’t tell’ phase also where I worked on it on the side,” she says. “I couldn’t talk about it, really. It was a bit isolating — until recently.”

Fejzo started her first HG study in 2000 by posting a survey about pregnancy nausea on the Internet. Responders faxed their answers to her. One of the women who took the survey was Kimber MacGibbon, who had HG and went on to co-found the HER Foundation, dedicated to research, education, and support for those with HG.

Researchers worry that drugs to treat pregnancy nausea won’t be commercially viable because it’s a “one or two shot” drug, only for use during pregnancy. “They like making drugs that people need forever.”

Over the next several years, Fejzo continued collecting survey responses and DNA samples, and she began enrolling participants in a larger study that showed HG ran in families. In 2010, after receiving a 23andMe kit for her birthday, Fejzo reached out to the company and asked if it would include questions on its surveys related to HG. And over the following decade, Fejzo tried to connect all the dots.

Her research found that HG was related to a hormone known as growth differentiation factor-15 (GDF15). But she didn’t know exactly how GDF15 affected nausea in pregnancy— until recently.

In a paper published in Nature in December 2023, Fejzo and her co-authors showed that the likely main cause of severe pregnancy nausea is, in particular, the pregnant person’s sensitivity to GDF15.

GDF15 is related to appetite suppression and nausea. Most people have a certain level of GDF15 in their bodies, but the amount of GDF15 depends on genetics and on circumstances — it can increase with age or when cells become stressed, like during an illness. (This is why, for example, cancer patients can also experience nausea and suppressed appetite.)

Researchers worry that drugs to treat pregnancy nausea won’t be commercially viable because it’s a “one or two shot” drug, only for use during pregnancy. “They like making drugs that people need forever.”

In pregnancy, the fetus produces GDF15 in large amounts. If a pregnant person starts out with higher GDF15 as their baseline, then the increase in pregnancy may not hit them so hard, and they have less risk of severe nausea. If a person starts out with lower GDF15, that increase can lead to higher risk of pregnancy nausea. The amount of GDF15 that the fetus produces is genetic, too, which is why the level of GDF15 — and the nausea it causes — can vary for different pregnancies.

After more than 20 years of researching the cause of HG, much of it without institutional support, Fejzo wants to see this to the end. She wants a treatment for HG that works. “I’m trying to do my best to help get this to its final chapter,” she says. “It’s been a long hard road.” She gets emails fairly regularly from HG patients asking her when there will be a cure. “People are always writing nice things, but it is also a lot of pressure,” Fejzo says. But now she can see a clear way forward.

In fact, there may be multiple ways forward. One path to easing HG symptoms is to create a medication that blocks the brain from receiving the GDF15 hormone, leaving the pregnant person less affected by the increase during pregnancy.

Stephen O’Rahilly, a geneticist and co-author of the paper published in December, knows there will be barriers for companies to develop this kind of drug. The litigious environment in the United States makes it almost impossible for the drugs to be tested in the country — most pharmaceutical companies don’t want to take the risk of testing drugs for pregnant people. He expects it will be developed elsewhere first.

Based on the research Fejzo and O’Rahilly published, the pharmaceutical company NGM Bio is currently working toward development of one such drug. According to its website, it is planning a study for the treatment in pregnant women. (The company did not respond to request for comment.)

“People still maybe don’t understand how bad this disease is and how much better prevention or treatment methods are needed. Even though I’ve been trying and trying.”

But there’s a commercial fear, O’Rahilly says, that the drug won’t be profitable. He’s seen companies say that drugs that treat pregnancy nausea won’t be commercially viable because it’s a “one or two shot” drug, only for use during pregnancy. “They like making drugs that people need forever,” he says.

Even so, he’s convinced the rationale to safely treat pregnancy nausea by blocking GDF15 receptors is sound. And there is an enthusiastic demand for treatment, whether companies think it will be profitable or not. “There will be an effective and safe treatment, certainly within my lifetime but hopefully well before that,” he says. “I’ve never been more confident in a medical prediction.”

Another way forward is to lessen the sensitivity to GDF15 with a medication that safely increases the baseline GDF15 in someone’s system before pregnancy. Drugs that happen to increase GDF15 already exist, some with decades of safety information available. It’s this scenario that Fejzo is ready and waiting to test. She has a clinical trial ready to go — but she needs funding. One grant she applied for was just rejected.

In the meantime, pregnant people like Olivia Myers are desperate for treatment. By Myers’ 14th week of pregnancy, her doctor suggested she reach out to the Morning Sickness and HG Clinic of Birmingham, Alabama. The clinic, which opened in October 2022, is the first of its kind: a place created to treat severe pregnancy nausea.

Instead of getting the up to 2% of pregnancies from the state — the amount estimated to have severe HG — it is getting closer to 5%. In addition to providing one-on-one care for HG patients, making adjustments to medication as needed, and providing regular IV infusions, the clinic is amassing blood samples and data to advance research and care for HG.

“As soon as I gave birth to her, all of my symptoms went away. I went from taking 13 medications to one,” says Myers.

Myers says that after regular visits to the clinic, her symptoms did improve. There were still days she couldn’t get out of bed, but they were fewer and farther in between, and after several months of treatment and regular IVs, she delivered a baby girl. “As soon as I gave birth to her, all of my symptoms went away. I went from taking 13 medications to one,” she says.

Despite the demand and effectiveness of its care, Dr. Andrew Housholder, the clinic’s founder, says it is facing trouble getting insurers to pay for the treatment provided. “I spent hours yesterday trying to gather data to convince them to pay for some of the medicines that we give patients,” he tells me. “We are trying to figure out how to help them see that we are saving them a lot of money by treating them out of the hospital and outside of the ER.” For now, even with exponential growth in the patients it serves, the clinic is operating at a loss.

More morning sickness clinics are beginning to open, with the help of Fejzo, who seems to have a hand in every bit of progress related to HG. She connected with Housholder in 2023 to discuss his clinic, and she brought what she learned to the Harmonia Healthcare treatment center, where she’s chief scientific officer. The Morning Sickness Clinic staff in Alabama helped train the staff at the Harmonia Clinic, which opened its first location in New Jersey in May. Harmonia is planning to open two more locations, in New York and Philadelphia, later this year.

When the first Harmonia treatment center opened, the response was overwhelming, says President and co-founder Leslie Gautam. It got calls from all over: Germany, Mexico, and across the United States. They help whomever they can, directing those from out of town to resources they can use. The patient from Mexico happens to have family near the clinic, so she is flying in for treatment. “Women have been suffering with this,” Gautam says. But prioritizing treatment as a society and educating people on the realities of HG has been lacking.

“People still maybe don’t understand how bad this disease is and how much better prevention or treatment methods are needed,” says Fejzo. “Even though I’ve been trying and trying.”

“So yes, I want another child. Am I confident that I want to go through that again? No.”

Myers’ baby girl, Eileen, is now about 9 months old. The baby coos and plays when I talk to Myers over FaceTime. Myers always wanted multiple children, but after dealing with HG, she’s unsure. “For the first three months, I was like, ‘I’m never gonna be pregnant again,’” she says. Now that time has passed, she and her husband are discussing next steps. They talked about adoption. She’s considering pregnancy again.

If she does choose pregnancy again, she says she is going to go to the Morning Sickness Clinic sooner. She believes having resources available to get ahead of the dehydration would help immensely.

But she’s still not sure she can face it. “You still kind of have this trauma response from going through that, where you’re like, ‘Oh, my God, I just don’t know if I can do it,’” she says. “So yes, I want another child. Am I confident that I want to go through that again? No.”

Fejzo was able to use a surrogate to have her twin daughters after a miscarriage. “I’ve been fortunate in that I’ve been able to complete my family after this horrible experience. And not everyone with HG is that fortunate,” she says. She works hard so that, one day, fewer people will need to make these kinds of decisions because of the disease. And because of her, that day may finally come.

Rae Nudson is a freelance writer with an interest in women's health care and mental health. She is the author of All Made Up: The Power and Pitfalls of Beauty Culture, from Cleopatra to Kim Kardashian.