Kathryn started taking Ozempic “off label” in April 2023 on her doctor’s advice. The Illinois resident had been diagnosed with gestational diabetes while pregnant and was struggling with her weight after the birth of her daughter. Following a short break from the drug in July because of side-effects, she started taking it again in August. In September, she found out she was pregnant.
Although Kathryn wasn’t using contraception, the pregnancy still came as a surprise. She had been told by doctors that she was unlikely to conceive naturally, and had been through several unsuccessful rounds of intrauterine insemination (IUI) before giving birth to her first child via IVF. “It was completely unexpected,” Kathryn tells me. “We hadn’t really planned to grow our family quite so soon – my first daughter was only 13 months old.”
Ozempic is a type 2 diabetes medicine, not a fertility treatment. But stories like Kathryn’s aren’t rare. In fact, there’s a whole registry dedicated to monitoring women who have fallen pregnant while taking Wegovy, a weight loss medicine that contains the same active ingredient as Ozempic. Other women are sharing their stories on X under the hashtag #OzempicBabies.
The weight loss triggered by this class of drug is likely to be driving these surprise pregnancies, says Adam Balen, consultant in reproductive medicine at Leeds Teaching Hospitals. Carrying extra weight negatively affects women’s fertility in several ways, including inhibiting ovulation and reducing the quality of their eggs and womb lining, he explains. So when overweight or obese women lose weight, their chances of conceiving tend to get better.
But there’s also another theory that posits that drugs such as Ozempic may interfere with the efficacy of birth control pills. These new diabetes and weight loss medicines mimic a natural gut hormone called GLP-1 that has three main functions – boosting insulin, slowing the emptying of the stomach and acting on parts of the brain that regulate hunger. It’s the second function that could hamper the body’s absorption of oral contraceptives, leading to surprise pregnancies.
One big pharma company, Eli Lilly, is advising women to switch to non-oral contraception or a barrier method when starting off on its drugs Mounjaro or Zepbound, or when moving to a higher dose. Both Mounjaro and Zepbound contain the GLP-1 agonist tirzepatide.
However, there is no evidence that this theory also applies to Ozempic and Wegovy, which are made by Novo Nordisk and contain a different compound called semaglutide. A spokesperson for Novo said that its drugs didn’t change the overall exposure to the active ingredients in the combined pill “to a clinically relevant degree” in the company’s clinical trials.
“The whole contraceptive pill issue is still a little uncertain in terms of the extent to which it’s influencing these pregnancies,” Balen says. The absorption factor could have some bearing but weight loss is likely to be the bigger reason, he adds.
This phenomenon has led some researchers to speculate that GLP-1 drugs could improve fertility in relation to the most common cause of anovulation in women – polycystic ovary syndrome (PCOS). The condition affects around one in 10 women and symptoms include irregular periods, excess body hair and weight gain. It was one of the reasons Kathryn struggled to become pregnant with her first child.
PCOS patients are often prescribed the birth control pill to regulate their periods, but this doesn’t address the root mechanisms of the condition and it certainly doesn’t help with fertility.
Melanie Cree, director of the University of Colorado’s PCOS multidisciplinary clinic, is the main investigator on a clinical trial testing semaglutide in 80 obese girls and women with PCOS aged 12 to 35. She explains how GLP-1 drugs are thought to encourage ovulation in the condition.
In around 80% of people with PCOS, the finely tuned system of hormone secretions needed for ovulation is off sync, Cree says. This hormonal imbalance is driven by two mechanisms – problems with the brain’s hypothalamus and insulin resistance. The latter occurs when the body’s cells don’t respond well to the hormone that regulates blood sugar.
Insulin resistance can get better if patients lose weight, which is why women with PCOS are often advised to do so at diagnosis. The idea is that the weight loss triggered by GLP-1 drugs can improve insulin sensitivity and thus restore the right hormonal balance for egg release.
There could also be another mechanism at play, according to Cree. In pilot MRI studies, her team noticed changes in brain connectivity in women with PCOS taking semaglutide. “The part of the brain that senses calories, the hypothalamus, was better connected to the parts of the brain that do decision making,” she tells me. “We don’t know neurologically what exactly that is – is that just related to appetite or is there something more there?”
For the most part, however, weight loss seems to be the main driver, Cree says. Based on her earlier research on the syndrome, she says that semaglutide probably won’t have an effect on patients who are at an ideal weight. While 80% of women with PCOS have BMI values above normal or high, the rest present with what is known as a lean phenotype, according to research published in the Journal of Diabetes & Metabolic Disorders.
This prompts the question: do GLP-1 drugs do anything special in women with PCOS that they don’t do in overweight or obese women generally?
There’s probably more of an effect on insulin levels in women with PCOS than in overweight or obese women who don’t have PCOS, says Colin Duncan, principal investigator at the MRC centre for reproductive health at the University of Edinburgh, who is not involved in the Colorado trial. The fertility improvement could therefore be more dramatic in women with PCOS, he says.
Furthermore, PCOS patients could stand to benefit more from a medicated approach to weight loss because they have metabolism problems that make shedding pounds more challenging. In a process known as postprandial thermogenesis, a woman with PCOS burns about 75% of the calories that a weight-matched healthy woman burns after eating a meal, Duncan says.
“That means that every single day, [women with PCOS] have to, say, exercise 20% more or eat 4% less to be the same as anybody else,” he says. “I think it can be very disheartening for women who struggle with their weight, so to have something that helps kickstart weight loss alongside lifestyle changes, from a psychological and wellbeing point of view, could make people better able to maintain weight loss,” Balen says.
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Afua, who lives in the UK, also struggled with her weight and fertility. Her first son was conceived a year and a half into her journey working with PCOS-specific nutritionists to optimise her diet to help her ovulate. While she didn’t lose any weight, she did manage to get pregnant naturally in 2020. “I found out on my birthday – it was a good present,” she says.
Two years later, Afua started taking Ozempic at the recommendation of her private endocrinologist and lost 30kg in less than nine months “like it was nothing”. When she was ready for another child, Afua stopped taking the drug and found herself pregnant with her second son just four months later. “Ozempic totally changed my life,” she says.
The problem is that GLP-1 drugs aren’t recommended for women trying to conceive because of safety concerns about the potential for abnormal development of the baby, Balen says.
The US Food and Drug Administration advises women to stop taking Ozempic at least two months before a planned pregnancy. Kathryn, who became pregnant while taking Ozempic, was advised to come off it right away – her second daughter is healthy.
But even if they are used correctly, access to GLP-1 drugs is another challenge.
Novo has recently got its supply of Ozempic and Wegovy back on track after several years of intermittent shortages in the US. More importantly, these drugs are approved only for a handful of conditions, and PCOS is not one of them.
The UK’s National Institute for Health and Care Excellence recommends Ozempic for patients with uncontrolled type 2 diabetes who have a BMI of 35 or more and another weight-related health concern, such as high blood pressure. It can also be given to people with a lower BMI if they are unable to use insulin owing to the risk of low blood sugar.
But GLP-1 drugmakers are working to unlock new indications for their drugs in other weight-related conditions. In July, the UK’s Medicines and Healthcare products Regulatory Agency approved Wegovy to reduce the risk of serious heart problems or stroke in overweight and obese people.
“It would be nice to think that PCOS might be one of those things over and above obesity that would allow access to these medications,” Duncan says.
In the meantime, the syndrome is taking its toll on health spending. An article published in July in the Journal of Clinical Endocrinology & Metabolism by researchers at Cardiff University shows more people are being diagnosed with PCOS. They estimated that the cost of treating the condition in the UK was more than £1.2bn in 2019.
For Afua, Ozempic is a no-brainer. “Even my partner said to me, as soon as you’re done breastfeeding, if you’re ready, we’ll put you back on Ozempic, because he could just see how much of a smile the benefits put on my face,” she says. “I think doctors, the NHS, everyone, just need to be more aware of what is out there and what can actually help.”
