Managing obesity-related male infertility: insights from weight loss intervention
Thairo A. Pereira, Nirja Thaker, André Canettieri Rubez, Victor Luiz de Souza Lima, Helen L. Bernie, Sandro C. Esteves
Abstract
Obesity is a global health concern with major implications for male reproductive function. It disrupts endocrine and metabolic homeostasis, impairs semen quality, and is associated with reduced pregnancy and live birth rates. Hormonal imbalances, inflammation, and lipid stress are key contributors to these impairments. This mini-review summarizes current evidence on the impact of therapeutic interventions, including lifestyle modification, bariatric surgery, and pharmacological approaches such as glucagon-like peptide-1 (GLP-1) receptor agonists, on male fertility outcomes. Lifestyle interventions, particularly moderate-intensity exercise and dietary improvements, are first-line therapies and should be routinely encouraged. Caloric restriction and Mediterranean-style diets rich in antioxidants have been associated with improved semen quality and hormonal balance. Bariatric surgery raises testosterone levels and may improve sperm quality and assisted reproduction outcomes in some men, but declines in sperm concentration and cases of postoperative azoospermia have also been reported. These findings underscore the importance of preoperative fertility counselling and consideration of sperm cryopreservation. GLP-1 receptor agonists promote weight loss and may improve sperm motility and hormonal markers; however, isolated cases of reversible impairment in sperm quality have been reported. Despite growing clinical use of these interventions, it remains unclear whether the observed benefits stem from weight loss itself or the specific treatment modalities. Longitudinal studies are needed to determine whether fertility improvements translate into higher conception rates. The reproductive safety of GLP-1 agonists in the preconception period also warrants further investigation. We recommend prioritizing pragmatic clinical trials with functional fertility endpoints, as well as mechanistic studies in well-characterized male obesity phenotypes and evaluation of offspring health. Ultimately, a shift is necessary from a narrow focus on weight loss to a broader emphasis on enhancing metabolic health. Personalized approaches tailored towards hormonal profiles, comorbidities, and fertility goals, supported by behavioural counselling and multidisciplinary care, are essential for advancing the treatment of obesity-related male infertility.