From the Guidelines
GLP-1 receptor agonists may have a positive effect on fertility, particularly in individuals with polycystic ovary syndrome (PCOS) or obesity-related infertility, as suggested by a recent systematic review and meta-analysis 1.
Key Points
- Medications such as exenatide, liraglutide, and semaglutide may be associated with improved fertility outcomes, including increased pregnancy rates, as seen in a trial comparing pregestational exenatide to metformin 1.
- However, the evidence is not yet strong enough to support their use as a primary fertility treatment, and further research is needed to fully understand the effects of GLP-1 receptor agonists on fertility.
- It is essential to consult with a healthcare provider to discuss the potential benefits and risks of GLP-1 receptor agonists in the context of fertility, considering individual circumstances and weighing the potential benefits against the increased risk of adverse events (AEs) compared to controls, including metformin 1.
- Typical doses used for other indications, such as type 2 diabetes, range from 0.5 to 1.8 mg per day for liraglutide and 0.5 to 1 mg per day for semaglutide, but the optimal dose and duration for fertility purposes are unknown.
- The interest in using GLP-1 RAs in women with PCOS has increased due to their general efficacy in weight reduction, which may also contribute to improved fertility outcomes 1.
From the Research
Effects of GLP-1 Receptor Agonists on Fertility
- GLP-1 receptor agonists (GLP-1 RAs) may have a stimulating role in mammalian reproduction, beyond mere weight reduction 2.
- Preliminary data from interventional clinical studies suggest improved menstrual regularity and increased fertility rates in overweight and/or obese women with polycystic ovary syndrome (PCOS) treated with GLP-1 RAs in the preconception period 2.
- GLP-1 RAs and dipeptidyl peptidase-4 (DPP-4) inhibitors can reverse polycystic ovary morphology in preclinical models and decrease serum concentrations of androgens and their bioavailability in women with PCOS 2.
Mechanisms and Therapeutic Perspectives
- The administration of GLP-1 RA, mainly liraglutide, alone or in combination with metformin, has been investigated in women with obesity and PCOS, demonstrating significant weight loss and testosterone reduction 3.
- Exenatide and liraglutide are considered good options for the treatment of PCOS, especially in overweight or obese women, and those with glucose intolerance or cardiovascular disease risk factors 4.
- GLP-1 RAs may help regulate menstrual dysfunction and improve fertility outcomes in women with PCOS, although more research is needed to fully understand their effects on the hypothalamic-pituitary-gonadal axis 5.
Current Research and Future Directions
- Larger interventional studies are needed to establish the role of preconception intervention with GLP-1-based therapies, assessing fertility outcomes in obesity, PCOS, and diabetes-related fertility problems 2.
- The potential impact of the dose- and exposure time-response of different GLP-1 RAs needs further exploration, as well as the investigation of sex-specific variability of GLP-1 on reproductive outcomes 2.
- Future research should focus on the therapeutic potential of GLP-1 RAs in achieving targeted approaches for the treatment of PCOS and reproductive dysfunction 5.