The effects of glucagon-like peptide-1 receptor agonists on fertility, contraception, and pregnancy: clinical perspectives.

Abstract

Objective: This debate paper aims to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), whose use in obesity and diabetes management has rapidly expanded, on fertility, contraceptive efficacy, and pregnancy outcomes in reproductive-aged individuals, and to provide evidence-based clinical guidance.

Main arguments/evidence: GLP-1 RAs improve fertility in obese women with polycystic ovary syndrome (PCOS) through weight reduction and enhanced insulin sensitivity, meta-analyses demonstrated significantly higher spontaneous pregnancy rates. However, gastrointestinal side effects may theoretically compromise the absorption of oral contraceptives. Animal studies indicate potential foetal risks, and limited human data support discontinuation before conception with appropriate washout periods (2-4 weeks for short-acting agents, 8 weeks for semaglutide and tirzepatide). In men, metabolic improvements may indirectly enhance reproductive parameters. From a contraceptive perspective, non-oral hormonal methods and long-acting reversible contraception may represent more reliable options during treatment, particularly in the presence of gastrointestinal side effects that could compromise oral drug absorption.

Conclusions: GLP-1 RAs are valuable adjuncts in managing obesity-related infertility, particularly in patients with PCOS. Clinicians must counsel patients regarding contraceptive reliability during treatment, ensure adequate washout before attempting conception, and recognise that while fertility benefits are well documented, pregnancy safety data remain limited.