Can Ozempic (semaglutide) improve fertility in patients with Polycystic Ovary Syndrome (PCOS)?

Can Ozempic (Semaglutide) Improve Fertility in PCOS Patients?

Semaglutide shows promise for improving fertility in PCOS patients primarily through weight loss and metabolic improvements, but current evidence is extremely limited with only one small pilot study specifically examining semaglutide in PCOS, and it is not approved or recommended as first-line fertility treatment. 1

Current Evidence Status

The 2023 International Evidence-based Guideline on PCOS explicitly states that published data examining anti-obesity agents (including GLP-1 receptor agonists like semaglutide) in women with PCOS are very limited, and further research is urgently needed. 1 This represents a critical knowledge gap given that:

• Semaglutide appears to be the most potent long-acting GLP-1 RA available, but has only been studied in one small pilot study in PCOS patients 1
• Most existing GLP-1 RA studies in PCOS used suboptimal medication doses and short 12-week protocols, limiting the ability to demonstrate changes in important clinical outcomes like fertility 1
• Quality trials are woefully inadequate given the prevalence and impact of PCOS 1

Mechanism of Potential Benefit

Weight loss is the cornerstone mechanism by which semaglutide could improve fertility in PCOS patients. Even modest weight loss of 5% can improve both metabolic and reproductive abnormalities in women with PCOS, including restoration of regular menses and improved response to ovulation-inducing medications. 2, 1

Key metabolic improvements that support fertility:

• Reduction in insulin resistance, which disrupts the hypothalamic-pituitary-ovarian axis in PCOS 3
• Improved ovulatory function through metabolic optimization 3
• When combined with lifestyle interventions, liraglutide (a related GLP-1 RA) helps preserve lean body mass compared to medication alone 1

Current First-Line Fertility Treatments for PCOS

Clomiphene citrate remains the first-line medical treatment for infertility in women with PCOS in the absence of other male or female causes of infertility. 4, 3 The established treatment hierarchy is:

1. Lifestyle modifications (weight loss when necessary, physical exercise, smoking cessation) 4
2. Clomiphene citrate or letrozole (aromatase inhibitor) as first-line ovulation induction 5, 3
3. Direct FSH stimulation using low-dose protocols if clomiphene unsuccessful 5, 6
4. Laparoscopic ovarian drilling as alternative to gonadotropins, particularly in thin patients with high LH concentrations 6, 3
5. Assisted reproductive techniques (IVF/ET) when all else fails, which produces excellent results 6

Clinical Recommendations for Semaglutide Use

If considering semaglutide for PCOS-related infertility, it should be positioned as an adjunct to optimize metabolic status prior to conception attempts, not as a direct fertility treatment:

• Physical activity, specifically resistance training, should accompany GLP-1 RA treatment to preserve lean body mass and promote weight maintenance 1
• Healthcare professionals should engage in shared decision-making with PCOS patients, considering both potential benefits and adverse events when using GLP-1 RAs 1
• All GLP-1 RAs consistently resulted in greater adverse events than controls, including compared to metformin 1

Critical Safety Considerations

Semaglutide must be discontinued before attempting conception as GLP-1 receptor agonists are not approved for use during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) does not specifically mention GLP-1 RAs in their guidelines for PCOS management during pregnancy. 2

For pregnancy planning:

• Metformin appears to be safe during pregnancy according to ACOG guidelines, though documentation on its effects in early pregnancy is limited 2
• Consider transitioning to treatments with more established safety profiles in pregnancy if conception is imminent 2
• Monitor for pregnancy complications that occur at higher rates in women with PCOS 2

Comparison to Other GLP-1 RAs

Among GLP-1 receptor agonists studied in PCOS:

• Liraglutide and semaglutide demonstrate more clinical benefits for PCOS compared to shorter-acting GLP-1 RAs like exenatide 1
• Exenatide used twice daily did not confer significant benefits over metformin and was associated with more adverse events 1
• Longer-acting GLP-1 RA medications have advantages with improved adherence, glycemic effects, and tolerance compared to shorter-acting options 1

Bottom Line

Use semaglutide in PCOS patients seeking fertility only as a pre-conception metabolic optimization strategy, not as a fertility treatment itself. Discontinue well before attempting conception, transition to established first-line fertility treatments (clomiphene citrate or letrozole), and ensure appropriate metabolic monitoring throughout. The role of anti-obesity agents in PCOS management should be a high priority for future research. 1