JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):239
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263842

P-227. The Impact of GLP-1 Receptor Agonists on Female Reproductive Health

¹ Gabriel Monteiro Pinheiro, ¹ Catarina Favero Monteiro Pinheiro

¹ Embrionare - São Paulo – SP - Brasil

Objective: To evaluate the potential effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on female reproductive health, including ovulatory function and pregnancy outcomes, and to synthesize current clinical evidence.
Methods: A narrative review was conducted, encompassing experimental studies, clinical trials, and recent reviews on the effects of GLP-1 RAs on female reproductive health, published between 2010 and 2025. Literature searches were performed in PubMed and the Cochrane Library using a PICO-based strategy, and fourteen references were included in the final analysis after screening for relevance.
Results: Obesity is one of the fastest-growing health conditions worldwide and in Brazil, particularly among individuals of reproductive age. Its impact extends beyond metabolic and cardiovascular health, directly influencing fertility and pregnancy outcomes. In this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged not only as effective agents for weight reduction and metabolic improvement, but also as potential modulators of reproductive health. Most clinical research has focused on women with polycystic ovary syndrome (PCOS), where GLP-1 RAs have been associated with improved ovulation and assisted reproduction outcomes. In studies using exenatide and liraglutide, ovulation rates and menstrual frequency consistently improved when menstrual regularity was assessed as a primary endpoint. A prospective trial in 28 obese infertile PCOS patients demonstrated higher cumulative pregnancy rates over 12 months (69.2% vs. 35.7%) and higher pregnancy rates per embryo transfer (85.7% vs. 28.6%) in patients treated with GLP-1 RA plus metformin compared to metformin alone. GLP-1 RAs also reduce circulating androgen levels, although the underlying mechanisms remain unclear. Although ovarian reserve is highlighted as a key reproductive outcome, no clinical studies directly assessing the impact of GLP-1 RAs on ovarian reserve have been reported, representing an important gap in current evidence. Emerging animal evidence suggests direct reproductive effects of GLP-1 RAs beyond metabolic benefits. GLP-1 receptor expression has been identified in the hypothalamus, where it regulates GnRH pulsatility and increases LH secretion. Mouse studies further demonstrate that GLP-1 influences estrogen and progesterone levels, promotes follicular maturation, and may modulate GnRH neurons via kisspeptin (Kiss-1) pathways, which are essential for fertility. Additionally, GLP-1 RAs exert anti-inflammatory and antioxidant effects and improve lipid metabolism, potentially contributing to a more favorable environment for ovulation, implantation, and early pregnancy maintenance. Although GLP-1 RAs are contraindicated during pregnancy and should be discontinued at least two months before conception due to potential fetal toxicity, a recent study including 543 pregnancies exposed to GLP-1 RAs for weight management found no significant increase in overall adverse obstetric outcomes. However, an increased risk of preterm birth was observed, particularly among women with pre-existing diabetes, emphasizing the need for careful peri-conception planning. Clinical data remain limited, and most available studies have used liraglutide, while newer agents such as semaglutide and tirzepatide may offer greater efficacy. Nevertheless, the direct effects of these newer molecules on female reproductive outcomes remain unexplored, representing an important opportunity for future research.
Conclusion: GLP-1 receptor agonists represent a promising therapeutic option at the interface of metabolic and reproductive health. Current evidence, particularly in women with PCOS, suggests improvements in ovulatory function, menstrual regularity, and reproduction outcomes, in addition to their well-established metabolic benefits. Given the growing use of GLP-1 RAs among women of reproductive age, there is an urgent need for high-quality clinical trials to clarify their impact on ovarian reserve, natural fertility, and pregnancy outcomes. Expanding research in this field may not only optimize reproductive care for women with metabolic disorders but also open new opportunities for fertility-preserving interventions in broader populations