Ozempic and Fertility: Understanding the Potential Benefits and Risks.

Ozempic is EVERYWHERE. Everyone’s talking about… and sometimes it feels like everyone in NYC is on it. And that’s why this fertility doctor put together this helpful guide on what Ozempic is, how it works, and the potential benefits/risks for fertility – and an important PSA regarding Ozempic and pregnancy. 

How does Ozempic work and what is it used for?

Ozempic (semaglutide) is a medication used to treat type 2 diabetes by controlling blood sugar levels. Ozempic activates something called the glucagon-like peptide 1 (GLP-1) receptor – this, in turn, reduces blood glucose by stimulating insulin secretion and lowering glucagon secretion. When blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. Blood glucose is also decreased by the medication causing a minor delay in how fast the contents of the stomach are emptied into the rest of the GI tract, limiting absorption of sugars from diet.

While Ozempic is not approved by the FDA for weight loss, some healthcare providers may prescribe it off-label for this purpose. There is limited research on the effects of Ozempic on infertility and weight loss, but some studies suggest that Ozempic may have both positive and negative impacts on fertility.

Positive Impact of Ozempic on Fertility:

Weight loss can improve fertility by reducing insulin resistance, regulating menstrual cycles, and improving hormone levels. Research suggests that even modest weight loss can improve fertility in women with obesity or polycystic ovary syndrome (PCOS) by helping to restore regular ovulation. Obesity and type 2 diabetes have been associated with low testosterone and erectile dysfunction. Correction of the underlying metabolic issues can improve testosterone levels and lead to better sperm quality and sexual function. As Ozempic can promote weight loss, it may have a positive impact on fertility in some individuals by improving their weight and metabolic health.

Negative Impact of Ozempic on Fertility:

On the other hand, some studies suggest that Ozempic could have potential negative effects on fertility by altering hormone levels. Ozempic can reduce levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are essential signals for coordinating regular ovulation. This is particularly a concern where ozempic is being used inappropriately to maintain a very low body weight. I have treated many women with hypothalamic amenorrhea in association with past extreme caloric deprivation and weight loss (ie. eating disorders). In my experience, this can lead to a sort of re-wiring of the pituitary gland (which secretes LH and FSH) and is not guaranteed to be reversible when normal body weight/nutrition is restored. It can be very frustrating to my patients who are recovered from eating disorders to find that they are still unable to ovulate due to a sluggish pituitary that never releases the hormones to cause ovulation. Ozempic use has also been associated with reduced testosterone levels in men, which can affect sperm production and male fertility. There is limited data on the impact of specifically ozempic on male fertility – but there are studies which demonstrate lower testosterone levels immediately after an ozempic infusion; and others that do not show an impact on testosterone. There is evidence of GLP-1 receptors existing in the testicular tissue in both the mouse and human model – which is evidence that ozempic may have direct impacts on testicular function.

Overall, the impact of using Ozempic for weight loss on infertility is not fully understood, and more research is needed. If you are considering using Ozempic for weight loss and are concerned about its effects on fertility, it is important to speak with your healthcare provider. They can help you understand the potential risks and benefits of Ozempic treatment in your individual case and to develop a treatment plan that is right for you. It is also important to keep in mind that weight loss is not a guarantee of improved fertility and that there may be other factors affecting your ability to conceive.

If/when to consider pausing ozempic prior to an egg retrieval

Given the slowed rate of the stomach emptying, this is something to keep in mind when it comes to undergoing anesthesia (where there is a risk of gastic (stomach) contents splashing up the esophagus and entering the airway (this is an anesthetic complication called aspiration). Many doctors who prescribe ozempic are advising patients take a break for ozempic for a few weeks prior to undergoing any procedures that involve sedation/anesthesia to lower the risk of aspiration– talk to your prescriber about this if you are planning to undergo any procedures (ie. egg retrieval) to make a plan on when to pause ozempic. If you are pausing it prior to your egg retrieval cycle starting, it should be fine to restart it after the egg retrieval is completed – but again, speak to your doctor who prescribes ozempic and your fertility specialist.

Why and When Ozempic should be stopped BEFORE getting pregnant:

If you have been using Ozempic (semaglutide) and are planning to conceive, it is important to discuss your plans with your healthcare provider. There are fetal health and safety concerns regarding Ozempic use during pregnancy. Ozempic is currently not recommended for use during pregnancy.

There is limited data on the effects of Ozempic use during pregnancy in humans, and the available data is conflicting.

Animal studies have shown that high doses of ozempic during pregnancy can lead to adverse effects on fetal development, including fetal malformations and decreased fetal weight. A recent study published in The Lancet Diabetes & Endocrinology found that the use of GLP-1 receptor agonists, a class of drugs that includes Ozempic, during pregnancy was not associated with an increased risk of major birth defects or other adverse pregnancy outcomes. However, the study was limited by a small sample size and the lack of long-term follow-up. Studies in pregnant rats have shown embryofetal mortality, structural abnormalities, and alterations to growth when administered during organogenesis at maternal exposures below the maximum recommended human dose (MRHD). Early pregnancy losses and structural abnormalities were observed in rabbits at doses below the MRHD. In cynomolgus monkeys, early pregnancy losses and structural abnormalities were observed at exposures of 10-fold or higher that of the MRHD. Salcaprozate sodium (SNAC), an absorption enhancer in the oral tablet has been shown to cross the placenta and reach fetal tissue in rats. Administration of SNAC to pregnant rats has shown an increase in number of stillbirths and a decrease in pup viability. There are no adequate and well-controlled studies in pregnant women.

The American Diabetes Association recommends that women who are pregnant or planning to become pregnant should avoid using Ozempic and other GLP-1 receptor agonists due to the limited safety data available. If you become pregnant while taking Ozempic, it is essential to speak with your healthcare provider immediately. They can help you understand the potential risks and benefits of continuing Ozempic treatment during pregnancy and develop a treatment plan that is right for you.

The duration of time you should wait to conceive after stopping Ozempic may depend on several factors, including the duration and dose of your Ozempic treatment and your individual health status. In general, it is recommended that you wait at least 2-3 months after stopping Ozempic before trying to conceive.

This waiting period allows time for Ozempic to be cleared from your system and for your body to readjust to its natural hormonal balance. 

References:

Caltabiano R, Condorelli D, Panza S, Boitani C, Musso N, Ježek D, et al.. Glucagon-Like Peptide-1 Receptor is Expressed in Human and Rodent Testis. Andrology (2020) 8:1935–45.

Cannarella R, Calogero AE, Condorelli RA, Greco EA, Aversa A, La Vignera S. Is There a Role for Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Male Infertility? Andrology (2021) 9:1499–503. 

Izzi-Engbeaya C, Jones S, Crustna Y, Machenahalli PC, Papadopoulou D, Modi M, et al.. Effects of Glucagon-Like Peptide-1 on the Reproductive Axis in Healthy Men. J Clin Endocrinol Metab (2020) 105:1119–25. 

Jeibmann A, Zahedi S, Simoni M, Nieschlag E, Byrne MM. Glucagon-Like Peptide-1 Reduces the Pulsatile Component of Testosterone Secretion in Healthy Males. Eur J Clin Invest (2005) 35:565–72.

Martins FF, Santos-Reis T, Marinho TS, Aguila MB, Mandarim-de-Lacerda CA. Hypothalamic anorexigenic signaling pathways (leptin, amylin, and proopiomelanocortin) are semaglutide (GLP-1 analog) targets in obesity control in mice. Life Sci 2023; 313: 121268.