Obesity-Medicine Advances Add Variables for Fertility Management

A newer and effective generation of drugs for diabetes and obesity are helping some patients for whom excess weight has hindered normal ovulation and fertility. Along with positive potential, however, these medications create a need for education on the complexities of co-managing weight and infertility.

Recent headlines in the popular press have touted the possibility that a generation of so-called “Ozempic babies” might be in the making, since GLP-1 receptor agonists allow some women with dysregulated cycles to lose enough weight (≥ 5%) for regular ovulation to return.

Whether a resulting baby boom will emerge is yet to be seen, but Cleveland Clinic obstetrics/gynecology specialist Deidre McIntosh, MD, notes that weight loss with or without the help of drugs can have this effect. The popularity of the new weight loss drugs, however, makes it especially important now to counsel patients of childbearing age about potential effects. This is true both for those who hope to become pregnant and those who want to prevent pregnancy.

Better counseling for patients starts with clinicians who are up to speed on mechanisms, risks and benefits of the medications. Dr. McIntosh recently completed a fellowship in obesity medicine to deepen her knowledge in response to the needs of patients in her OB/GYN practice. The topic of weight loss comes up frequently, she says; patients often want help with losing weight.

“I wanted to take my ability to educate them up a level,” says Dr. McIntosh. “The fellowship enabled me to feel more confident prescribing (for weight loss) and becoming actively involved in that aspect of my patients’ care.”

Reregulating ovulation

Not all the connections between excess weight and fertility are fully understood, but polycystic ovary syndrome (PCOS) is a key element and one of the most common causes of infertility. In women with PCOS, the ovaries create excess androgens, leading to imbalances that can cause a host of symptoms, including reduction or cessation of ovulation.

“Typically we're seeing that about 30% to 40% of women with PCOS have insulin resistance, and 40% to 80% of women with PCOS have overweight or obesity. Therefore we see higher leptin levels, higher inflammation levels and markers for that,” says Dr. McIntosh.

Semaglutides (Ozempic for diabetes; Wegovy for weight loss) and tirzepatide (Mounjaro for diabetes; Zepbound for weight loss) can create a cascade of effects that help cycles disrupted by PCOS begin to heal.

“Losing weight can be really difficult for women, especially with insulin resistance,” she says. “These GLP-1 or dual incretin receptor agonists actually work in the gut to increase GLP-1, a natural gut hormone. When that increases, weight decreases and insulin sensitivity increases and the gut microbiome regulates. When all of that comes back to normal, androgen levels decrease and the ovaries start functioning, resulting in normal fertility rates.”

GLP-1s and conception

That return to normal may be a gift to a patient who wants to expand her family, but the medications can present a Catch-22. While they help patients achieve meaningful weight loss, no data yet exists to confirm that the drugs are safe to take during pregnancy, so the FDA recommends against it.

“We caution women taking the drugs that they should have a washout period for about two months or so before they actively try to conceive,” says Dr. McIntosh.

Yet studies show that people who stop taking these injectables experience the return of symptoms. This puts at risk the weight loss that can normalize ovulation and make pregnancy possible. Patients who stop taking the drugs can take metformin, which was approved in 1994 as a diabetic agent and is safe in pregnancy, but they are likelier to maintain their weight loss if they have been practicing lifestyle changes along the way, says Dr. McIntosh.

“Metformin will help with that insulin sensitivity, but hopefully we’ve been supporting them in how to eat properly, exercise and keep that inflammation as low as possible,” she says.

For those who take oral contraceptives to prevent pregnancy, there is concern that the newer drugs’ slowing effect on gastric motility may interfere with absorption of the pill.

“The thought is that patients on injectables are titrating their doses every four weeks and during that time if they are on oral contraceptives they should be using a barrier protection to prevent pregnancy until they get on maintenance dosing.”

Another option, she adds, is for switch patients to a vaginal ring or IUD while taking GLP-1 injections.

For those who become pregnant while on the drugs

Patients who become pregnant while taking GLP-1 agonists require a clinical consultation.

“I would tell any of my OB patients who were on a medication that was not recommended for pregnancy that the risks and benefits have to be considered, and we have to have that conversation,” says Dr. McIntosh. “Generally, we recommend they do not take them. But if we have a medication that is not recommended during pregnancy, yet it’s the only medication that has controlled their condition, we need a conversation to help the patient decide what's in the best interest of her and her baby.”

Weight-related services

Dr. McIntosh advocates for an approach to care that addresses many factors influencing women’s reproductive health.

“In treating low-risk patients in our practice, we do pharmacotherapy, nutrition counseling, and we talk about behavior modifications,” she says. “Because I love exercise, I get into a lot of that with my patients. But I also refer out as necessary — to exercise physiology, endocrinology, nutritionists, weight management, and to behavioral health. I recommend anything I think can help patients, including online sources and books.”

The goal is always to connect patients to every resource that can improve their health.

“We have a lot of options,” she says. “We really try to get the patient as much help as possible.”