The effect of obesity interventions on male fertility: a systematic review and meta-analysis

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BACKGROUND: Obesity is a prevalent modifiable cause of male factor infertility. Preconception guidelines recommend men maintain a healthy weight; however, they provide limited guidance regarding methods or volume of weight loss for men with obesity. First-line interventions for weight loss involve lifestyle optimization (healthy diet and exercise), followed by pharmacotherapy or bariatric surgery in severe cases. Each modality has differing weight loss potential and complications for which the reproductive implications are currently unclear. OBJECTIVE AND RATIONALE: To synthesize the available evidence regarding the reproductive effects of obesity interventions in men with obesity. Where possible, to evaluate whether the observed effects depend on the magnitude of weight loss. SEARCH METHODS: Searches for articles published in English was performed using PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials and Scopus from inception until December 2024, using prespecified keywords pertaining to four categories: male, overweight/obesity, weight loss (bariatric surgery, nutrition, diet, lifestyle, exercise, pharmacotherapy) and fertility (conception, assisted reproduction, sperm, semen). Studies of reproductive-aged men (18-50 years) who underwent an obesity intervention with established weight loss benefits and undertook repeated assessment of reproduction capacity (semen analysis, conception rates, assisted reproduction outcomes) before and after the intervention were included. Meta-analysis was performed when two or more studies of the same modality assessed an outcome measure in a manner suitable for meta-analysis. A meta-regression considering weight loss achieved was performed when five or more suitable studies were available. Narrative review of studies not suitable for meta-analysis occurred. OUTCOMES: 32 studies were included in the analysis, with one study assessing both lifestyle interventions and pharmacotherapy. Assessment of conception rates and assisted reproduction was limited across all modalities. In almost all cases, the effect of obesity interventions on semen quality was examined as a surrogate for reproductive capacity and the certainty of evidence was low. Bariatric surgery was assessed in 18 studies, including 12 quasi-experimental studies, one randomized controlled trial, one case series and four case reports. Fixed- and random-effects meta-analysis of randomized controlled trials identified no differences in sperm parameters between control and intervention arms across any intervention, although small sample size limits interpretability. Random-effects meta-analyses of pre-post outcomes identified no clinically significant semen parameters or DNA damage changes following bariatric surgery. Pharmacotherapy (metformin and liraglutide) was assessed in five studies, including four quasi-experimental studies and one case report. There were insufficient data to draw clear conclusions regarding the impact of these agents on fertility outcomes. Lifestyle interventions were assessed in 10 studies, including five quasi-experimental studies and five randomized controlled trials. Fixed-effect meta-analysis identified improvements in sperm normal morphology (Mean difference = 0.59%, 95% Confidence interval = [0.23, 0.94]), and progressive motility (10.56% [8.97, 12.15]) following a lifestyle intervention. WIDER IMPLICATIONS: Data regarding weight loss interventions and male fertility is limited primarily to observational studies examining semen quality. Improvements in semen quality following lifestyle interventions suggest a potential benefit of optimizing nutrition and physical activity, whereas a limited change with bariatric surgery indicates obesity-associated sperm dysfunction does not resolve in a dose-dependent manner with weight loss and/or negative effects of rapid weight loss exist. Substantial knowledge gaps were identified, including limited randomized trials, inadequate examination of conception outcomes and limited assessment of GLP-1 agonist effects. REGISTRATION NUMBER: CRD 42022349665.

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