GLP-1 receptor agonists, reproductive function and pregnancy: metabolic benefits, fertility, and safety considerations

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an established therapeutic class for the management of type 2 diabetes mellitus and obesity. Their increasing use among women of reproductive age has raised important concerns regarding their potential impact on fertility, preconception care, and safety during pregnancy. Current evidence suggests that GLP-1RAs may exert beneficial effects on ovulatory function, menstrual regularity, and the inflammatory milieu, particularly in women with insulin resistance and hyperandrogenism. Potential effects on endometrial function, implantation, and maternal–fetal immune tolerance have also been discussed. Nevertheless, the available evidence regarding exposure during pregnancy remains limited. Findings from animal studies have raised concerns about fetal development, particularly with respect to skeletal ossification, skin development, and neurogenesis, whereas observational studies in humans appear somewhat reassuring regarding the risk of major congenital malformations, although they do not allow for definitive safety conclusions. Consequently, GLP-1RAs are not recommended during pregnancy, and women with reproductive intentions should receive individualized preconception counseling and guidance regarding an appropriate treatment discontinuation period prior to conception.