Erin T. Welsh, MA , 2025-05-07 14:28:00
Key takeaways:
- GLP-1 use may improve fertility for some women with obesity or polycystic ovary syndrome.
- Clinicians should counsel women about risk for unintended pregnancy when starting GLP-1 therapy.
GLP-1 receptor agonists remain blockbuster drugs for weight management for people with overweight or obesity. Increasingly, OB/GYNs and other specialists report observing fertility-related benefits that may accompany potent weight loss.
Originally approved for people with type 2 diabetes, several GLP-1 receptor agonists now have FDA indications for weight management, including once-weekly injectable semaglutide 2.4 mg (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly), an injectable GIP/GLP-1 dual incretin-based agonist. These medications also have FDA indications to treat sleep apnea, chronic kidney disease and reduce cardiovascular risk. Experts told Healio that GLP-1s could potentially hold benefit for women with infertility; data suggest select patient populations may benefit from preconception GLP-1 receptor agonist use when attempting pregnancy.
“I’m using GLP-1 receptor agonists for preconception weight loss and for patients interested in losing weight prior to pregnancy who want to be healthier and have decreased risk for gestational diabetes, hypertension and preeclampsia,” Johanna G. Finkle, MD, weight loss specialist and OB/GYN in the department of obstetrics and gynecology at the University of Kansas Health System, told Healio. “These women are losing weight and then going on to conceive.”
‘A new therapeutic option’
There is growing interest in GLP-1 receptor agonist use for improving fertility odds, especially for women with obesity and/or polycystic ovary syndrome. Data from small studies suggest preconception GLP-1 use may help improve pregnancy odds in this patient population.
In a meta-analysis and systematic review published in BMC Endocrine Disorders in 2023, researchers found that, among 840 women with PCOS across 11 randomized controlled trials, GLP-1 use was associated with an improvement in the rate of spontaneous pregnancy (RR = 1.72; 95% CI, 1.22-2.43; P = .002). There were no significant differences in the total pregnancy rate or IVF pregnancy rate between those prescribed a GLP-1 (n = 469) vs. those not prescribed a GLP-1 (n = 371). Women prescribed GLP-1s also saw improvement in metabolic parameters and a slight reduction in total testosterone compared with those who did not use a GLP-1. Additionally, the pooled result showed that adding GLP-1 treatment was more effective compared with metformin alone or placebo for improving menstrual frequency.
“It is worth noting that GLP-1 receptor agonist treatment in obese PCOS patients can be a new therapeutic option beyond the goal of weight loss,” the researchers wrote. “Still, more long-term, large-scale, multiethnic, phenotype-specific, well-designed trials are warranted to confirm the efficacy and safety of GLP-1s in preconception PCOS women.”
GLP-1 receptors are present in the ovaries, endometrium, and testes. In a review published in Obstetrics & Gynecology, Finkle noted that GLP-1 receptor agonists may exert anti-inflammatory effects on these tissues.
“However, further research is necessary in this emerging field,” Finkle wrote.
Christina E. Boots
For women with irregular menstrual cycles, GLP-1s can improve ovulation, which, in turn, helps improve fertility outcomes, according to Christina E. Boots, MD, MSCI, associate professor in the department of obstetrics and gynecology in the Center for Fertility and Reproductive Medicine at Northwestern University.
“For women who are not having regular menstrual cycles and consistent ovulation, these medications are going to help them to cycle more consistently,” Boots told Healio. “For those with unexplained infertility, we do not know yet if these medications are going to help. There are data not involving GLP-1s that have shown short-term acute weight loss prior to starting IVF has not improved live birth rates, though the data included women with a regular cycle. We do not have a big, randomized control trial with these newer medications in couples with unexplained infertility.”
Finkle has also observed improved ovulation among women with PCOS prescribed GLP-1 therapy who have lost 5% to 10% of their initial body weight.
“We’re seeing that patients with PCOS are having a return to ovulation with modest weight loss and research suggests this may be independent of the weight itself,” Finkle told Healio. “For patients with infertility, we are seeing an improvement in fertility but translation to an increase in live birth rates with IVF need to be studied. While weight loss with GLP-1 receptor agonists prior to IVF remains a controversial topic, as a weight loss specialist, I continue to work with patients and my reproductive medicine colleagues to meet patients’ goals as they relate to weight and fertility.”
Despite the possible benefits these medications may have on fertility, more research is needed because the medications are still new.
“At the moment, the data are mostly limited to patients who have PCOS,” Paula Amato, MD, MCR, professor in the department of obstetrics and gynecology and director in the division of reproductive endocrinology and infertility at Oregon Health & Science University, told Healio. “The few studies that have been done in that population show these medications are effective for weight loss and do seem to improve pregnancy rates.”
Women who may not benefit
A relatively young woman with ovulation dysfunction, irregular menstrual cycles and metabolic dysfunction may have improved fertility odds with GLP-1 receptor agonist use, according to Boots. However, initiating GLP-1 therapy for women aged 39 years or older who desire pregnancy may not be optimal because the decision could result in lost time trying to conceive while using the medication.
“Unlike dysglycemia and hypertension, which we can optimize in fairly quick fashion, weight loss takes time,” Richard S. Legro, MD, FACOG, chair of the department of obstetrics and gynecology at Penn State College of Medicine and Penn State Health in Hershey, Pennsylvania, told Healio. “Do you ask a 40-year-old women to take a year off [attempting pregnancy] to lose weight? You have to factor a woman’s age and ovarian reserve into any treatment plan.”
Paula Amato
There can be a “trade-off” for older women starting GLP-1 therapy, who risk decreased odds of pregnancy with increased maternal age, Amato said.
“You want to balance the benefits of weight loss vs. the benefits of getting pregnant — trying to get pregnant as soon as possible while your egg quality and egg numbers are good,” Amato said.
It remains unclear if women with obesity but without PCOS or type 2 diabetes could see a fertility benefit with GLP-1 use, Amato said.
“We just do not have the data to support that,” Amato said. “I’m hopeful that within the next few years, we’ll see the results of ongoing studies in this area.”
Potential drawbacks
Preconception GLP-1 receptor agonist use may improve fertility odds for some women, especially those with obesity or PCOS, but these drugs can also come with risk for adverse outcomes.
Use of a GLP-1 receptor agonist is associated with several gastrointestinal adverse effects, including nausea, vomiting, constipation and diarrhea; in rare instances, a person could develop pancreatitis. There are conflicting data on a possible association between GLP-1 use and suicidal ideation. Emerging data also suggest that lean muscle mass loss with GLP-1s could increase risk for osteoporosis among women.
There are also risks that come with substantial weight loss, Legro said.
“Part of the risk with weight loss, especially with restrictive bariatric procedures, is there is often malabsorption of key nutrients. How can we supplement for that during pregnancy?,” Legro said. “Does that also happen when we alter weight through lifestyle management? Are we somehow nutritionally depleting the women anticipating pregnancy? We have to look carefully at miscarriage and other outcomes, and that will take a combination of registries and randomized trials.”
“We cannot tell our patients: “If you lose weight, everything will be perfect,’” Legro said. “There are sequalae to weight loss that might not be beneficial.”
‘Ozempic babies’ and the role of contraception
Although weight loss associated with GLP-1s may improve pregnancy odds for some women, studies suggest that certain GLP-1s can also interfere with birth control, leading to an unexpected pregnancy during a time when clinicians recommend pregnancy be avoided.
The FDA currently classifies GLP-1 receptor agonists as class C for use in pregnancy, and these medications are not recommended during pregnancy.
In a 2024 literature review published in the Journal of the American Pharmacists Association that assessed six clinical trials, researchers found that tirzepatide had a greater impact on absorption of oral hormonal contraceptives compared with other GLP-1s.
“The rapid dose escalation and greater delay on gastric emptying enhance the impact on coadministered interacting oral medications,” the researchers wrote. “This difference in impact between GLP-1 receptor agonists and tirzepatide should be noted by practitioners when coprescribing tirzepatide with oral hormonal contraceptives, and appropriate patient education on the management of the interaction should be provided.”
For these reasons, it is important to counsel any woman prescribed a GLP-1 about pregnancy risks and recommend a reliable contraceptive method, such as long-acting reversible contraception, Finkle said.
“‘Ozempic babies’ have been in the news, where a pregnancy happens when patients are not preventing and not realizing that is a possibility,” Finkle said. “Clinicians must counsel patients to use effective contraception and stop any GLP-1 medications 2 months prior to attempting to conceive, all while working with the patient to create a plan to prevent of diminish weight regain after discontinuation of the GLP-1 medication.”
Metabolic changes that occur with meaningful weight loss — as well as nausea and other gastrointestinal adverse effects often attributed to early GLP-1 use — can mean a woman is not taking in adequate nutrients and calories, leading the body to use adipose tissue and energy already stored, Boots said.
“It is important that we are talking about getting pregnant at the time when we are not depriving ourselves of nutrition and energy,” Boots said. “The timing between when you’re using GLP-1s and when you get pregnant needs to be really thoughtful.”
In the event a woman becomes pregnant while taking a GLP-1, any risks to the fetus remain unclear, according to Finkle. However, data suggest there is no association between congenital or cardiac malformations and GLP-1 exposure in infants, Finkle said.
“We’re still learning about all the implications with GLP-1 use and incident pregnancies,” Boots said. “The newer generation medications are once weekly, so the half-lives are decently long, and it takes a full 4 to 8 weeks for the molecule to be completely outside of the system. We don’t know what these molecules do to a fetus or growing infant.”
‘Clinicians must carefully counsel patients’
For women who desire pregnancy, the conversation about if or when to initiate a GLP-1 should begin as early as possible, Boots said.
“Ideally, we are talking about these medications before women even start trying to get pregnant,” Boots said. “A great time to start the conversation is 2 years before trying to conceive, asking, ‘how do I optimize my health for this pregnancy I’m planning for in the near future?’ In my dream world, everybody would have that conversation much earlier.”
Amato said clinicians must carefully counsel patients about the risks and benefits of the drug class, particularly for anyone who struggles with infertility and has irregular menstrual cycles.
“As OB/GYNs, we need to be able to discuss the association of obesity with infertility, pregnancy complications and certain other health outcomes, and talk about the different modalities available for weight loss, which include medications and surgery,” Amato said. “Lifestyle changes are important, especially for maintenance of weight after you go off the medication. Like most weight loss medications, once you stop taking the GLP-1, there is a tendency to experience weight regain.”
Clinicians can also discuss non-GLP-1 medication options that could be used closer to conception or stopped when pregnancy is detected to safely avoid weight regain, Finkle said.
Physicians should also conduct a thoughtful preconception evaluation to identify possible thyroid issues, signs of insulin resistance, type 2 diabetes or elevated liver enzymes, as well as assess patients’ ovarian reserve, instead of “immediately blaming BMI,” Boots said.
“Screen women for the obesity-associated comorbidities like impaired glucose tolerance, diabetes and hypertension and treat those appropriately,” Legro said. “We are learning that more aggressive treatment of what we considered borderline or even ‘normal’ levels of glucose and blood pressure in the past are giving us improved obstetric outcomes during pregnancy. We should probably be treating these issues preconception.”
Experts agreed that conversations with women interested in using GLP-1s to improve pregnancy odds should be multidisciplinary and patient centered, considering patient goals, preferences and timelines.
“Sometimes it’s not the weight loss that’s going to improve their outcomes, but the weight loss that’s needed to be able to access these more advanced and successful treatments [because of BMI limits in some IVF programs],” Boots said. “Each woman has to have a conversation about how meaningful using these medications are going to be for them.”
For more information:
Paula Amato, MD, MCR, can be reached at amatop@ohsu.edu.
Christina E. Boots, MD, MSCI, can be reached at christina.boots@northwestern.edu and on X: @NorthwesternMed and @NM_ObGyn.
Johanna G. Finkle, MD, can be reached at jfinkle2@kumc.edu.
Richard S. Legro, MD, FACOG, can be reached at rlegro@pennstatehealth.psu.edu.
