JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):144
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263781

P-132. Impact of GLP-1 Receptor Agonists on Male Fertility: A Systematic Review of Human Studies

Arnold Peter Paul Achermann¹, Thairo Alves Pereira², Filipe Tenorio Lira Neto³, Sandro Cassiano Esteves¹

¹ ANDROFERT - Clinica de Andrologia e Reprodução Humana - Campinas - São Paulo – Brasil
² MD Anderson Cancer Center - United States
³ IMIP - Instituto Materno Infantil – Recife – PE - Brasil

Objective: To systematically evaluate the clinical effects of glucagon-like peptide-1 (GLP-1) receptor agonists on semen parameters in men, with a focus on potential implications for male fertility.
Methods: A systematic search was conducted across PubMed (n = 64), Embase (n = 25), Cochrane Library (n = 8), and Google Scholar (n = 803). After removing duplicates and applying predefined eligibility criteria, four human studies were included: two randomized controlled trials (RCT), one prospective interventional study, and one case report. Eligible studies assessed semen parameters before and after GLP-1 agonist treatment. Animal studies and reports on unrelated therapies were excluded. The GLP-1 agonists investigated were liraglutide and semaglutide. Extracted outcomes included sperm concentration, total count, motility, morphology, hormonal profile, and metabolic parameters.
Results: Three out of four studies reported improvements in at least one semen parameter following GLP-1 receptor agonist therapy: • Andersen et al. (2022) conducted an RCT in obese men undergoing a weight loss and maintenance program. Forty-seven men completed an 8-week low-calorie diet, with improved semen parameters. Of these, 37 were randomized to liraglutide, exercise, both, or placebo for 52 weeks. Improvements in sperm concentration and total count persisted among those who maintained weight loss, including liraglutide users. No detrimental effect on semen quality was observed with liraglutide. • La Vignera et al. (2023) studied 70 obese men with functional hypogonadism seeking fertility. Group A (n = 35) received gonadotropins (urofollitropin 150 UI 3x/week and hCG 2,000 UI 2x/week), while Group B (n = 35) received liraglutide (up to 3.0 mg/day) for four months. The liraglutide group showed greater reductions in body weight, BMI, and waist circumference, along with superior increases in testosterone, LH, FSH, SHBG, and erectile function. Semen analysis revealed significantly better sperm concentration, motility, and morphology. These improvements occurred without suppression of the hypothalamic–pituitary–gonadal (HPG) axis. • Grögeric et al. (2024) conducted an RCT in 25 men with obesity, type 2 diabetes, and functional hypogonadism. Participants received semaglutide (n = 13) or testosterone undecanoate (n = 12) for four months. Semaglutide significantly improved sperm morphology and induced greater weight loss and BMI reduction. Although the rise in sperm concentration did not reach statistical significance, spermatogenesis was preserved. In contrast, testosterone therapy raised testosterone levels but significantly reduced sperm concentration and total sperm count. • Fontoura et al. (2014) reported a case of a previously fertile man who developed marked oligoasthenozoospermia during low-dose liraglutide treatment (0.6 mg/day). Semen parameters normalized after drug discontinuation, resulting in a successful twin pregnancy through in vitro fertilization. Although causality cannot be confirmed, the case raises awareness of possible individual susceptibility.
Conclusion: Preliminary data suggest that GLP-1 receptor agonists, especially liraglutide and semaglutide, may have neutral or beneficial effects on male fertility, particularly in men with obesity-related hypogonadism. These agents appear to improve semen quality by promoting weight loss, optimizing metabolic health, and restoring HPG axis function without direct gonadal suppression. However, rare reports of adverse effects underscore the need for individualized evaluation. Larger studies are warranted to confirm safety and reproductive outcomes in men pursuing fertility.

References:
Andersen et al. R. Hum Reprod. 2022;37:1414-22.
Fontoura et al. Reprod Biomed Online. 2014;29:644-6.
Gregorič et al. Diabetes Obes Metab. 2025;27:519-28.
La Vignera et al. J Clin Med. 2023;12:672.