DRUGS TO TREAT OBESITY HELP BOOST FERTILITY
Researchers say the medications ‘wake up the ovaries’, resulting in raised pregnancy rates – but information on their safety is limited
A surprising thing is happening to some women on weight-loss drugs who have struggled with fertility issues: they are getting pregnant.
That is leading to questions about the safety during pregnancy of medications Ozempic from healthcare company Novo Nordisk and Mounjaro from medicine company Eli Lilly.
“I thought I couldn’t have any more kids,” says Torria Leggett, 40, who had been trying for another after her first child was born in 2018. In 2022, the social worker from the US state of North Carolina began taking Ozempic to treat obesity, then switched to Mounjaro.
As the pounds melted off, there was soon another reason to celebrate. She was expecting.
“The weight loss, that’s probably what jump-started it,” she says. “I couldn’t believe it.”
Stories such as these are encouraging doctors to use these GLP-1 (glucagon-like peptide 1) drugs – mainly used to help manage blood sugar levels in people with type 2 diabetes, and more recently to treat obesity – to treat polycystic ovary syndrome (PCOS), one of the leading causes of infertility globally.
Yet they are doing so without much data on the drugs’ impact on pregnancy.
“The ‘oops’ babies on Ozempic and Wegovy are happening all over the place,” says Melanie Cree, director of the PCOS clinic at Children’s Hospital Colorado in the US.
“It’s very exciting, but it is a bit scary because we are moving forward without all the data.”
The need for treatments is severe. Despite its prevalence, no drugs are approved for PCOS, and experts are divided on whether recommended diet programmes work. Some patients are willing to try almost anything, and the successes are tantalising.
GLP-1 drugs have been marketed for nearly 20 years to treat diabetes, and their use in obesity is fuelling a new market that is expected to hit US$100 billion in 2030.
The problem is that companies have not systematically studied GLP-1’s use in PCOS – and do not plan to any time soon.
In the absence of data, researchers are doing studies of their own to figure out if the drugs work for PCOS, and US regulators have asked the companies to collect any information they can about their use during pregnancy.
Long-term safety data limited
So far, the safety data looks promising. A recent study of the health records of 50,000 women with type 2 diabetes found no increase in birth defects among those who used the drugs in very early pregnancy compared with those who took insulin.
Still, the study’s authors say more confirmation is needed, especially in women without diabetes. Researchers from Copenhagen, Denmark, concurred last year in a review of GLP-1 drugs, saying that there is “limited information on their long-term safety, particularly concerning pregnancy outcomes”.
Reasons for concern come mostly from animal experiments. The active ingredient in Novo Nordisk’s drugs, semaglutide, has been linked to increased birth defects in animals.
Similar studies of Eli Lilly’s drugs have shown there “may be risks to the fetus” from exposure during pregnancy, the company says.
No one is sure how – or even whether – the drugs contribute to women becoming pregnant.
Weight loss is known to boost fertility in women with PCOS, and studies have shown that Saxenda, an older obesity drug, also raised pregnancy rates in women with the disorder who were overweight.
GLP-1s may also have hormonal effects that promote fertility and may blunt the impact of oral contraceptives. Some experts think the drugs might even have a role in male infertility.
Rekha Kumar, a reproductive endocrinologist at Weill Cornell Medicine in New York, says GLP-1 drugs “wake up the ovaries”, resetting the reproductive environment for normal function.
One thing is clear, Kumar says: “These patients are becoming very fertile.”
Pregnant people and those planning to get pregnant were excluded from trials of GLP-1s. Trial participants have been required to use contraception, and treatment was discontinued for those who became pregnant during clinical trials of Mounjaro and Zepbound, Eli Lilly says.
Conflicting advice
It’s very exciting, but it is a bit scary because we are moving forward without all the data
MELANIE CREE, PCOS CLINIC DIRECTOR
Experts are split on how soon patients should stop taking the medications before a planned pregnancy. Some doctors are telling patients that up to four weeks is safe; others say it is fine to keep using them up until the time of pregnancy.
Wegovy’s label says people should stop taking the drug at least two months before trying to get pregnant, while Zepbound’s recommends that people who become pregnant stop the drug.
In Colorado, Cree is running a study to find out how Novo Nordisk’s Wegovy affects ovulation in women with PCOS, but supply problems with the popular drug present a challenge. Novo Nordisk will not provide free supplies because the patients will not be on birth control, she says, a decision she calls “very disappointing”.
Meanwhile, a study found that the number of women exposed to GLP-1 drugs during early pregnancy appears to be increasing, as more turn to them for diabetes and other conditions.
The private Facebook group “I got Pregnant on Ozempic” has 630 members; on TikTok, dozens have said they have become pregnant while taking a GLP-1 drug.
The US Food and Drug Administration asked Novo Nordisk to set up a registry to collect data on those who got pregnant while taking
Wegovy, but the company has yet to share any results. It is also required to do another pregnancy study using insurance claims or electronic medical records, the FDA says.
Eli Lilly is planning to set up a similar registry but declined to say when. Meanwhile, Cree and a handful of researchers are scrambling to set up their own databases to track pregnancy outcomes in GLP-1 patients.
PCOS symptoms’ improve ‘significantly’
PCOS is a condition that typically involves irregular ovulation and high levels of male hormones called androgens. It is the most common hormonal disorder in women, putting them at increased risk of diabetes, heart disease and mental health issues.
Those with the condition frequently make too much testosterone, leading to effects like extra hair growth, acne and weight gain, and blocking ovulation. They also do not respond properly to insulin, and the weight-loss effects of GLP-1s may improve sensitivity to the hormone.
The new drugs “are not going to cure you, but [they are] going to improve the symptoms significantly”, says Ricardo Azziz, a PCOS expert and professor at the University of Alabama at Birmingham and State University of New York.
Still, he also thinks more data is needed before doctors recommend the drugs for fertility.
People like Leggett, who got pregnant on a weight-loss drug, have some questions. She sometimes wonders why her daughter is smaller than other kids the same age. “She is teeny-tiny,” Leggett says. “I’d like to know more about that.”