PMON259 Weight Loss using a Formula Low Energy Diet Reduces Seminal Oxidative Stress in Men with Obesity and Oligospermia: a Randomised Controlled Study

BACKGROUND: Poor sperm quality (male infertility) is present in 50% of couples requiring assisted reproductive technologies (ART). Few couples worldwide have access to ART, and there are currently no available drugs to improve sperm function. Obesity is a major cause of male infertility. Semen reactive oxygen species (ROS), is a recently identified mechanism for sperm DNA damage resulting in reduced fertilisation and pregnancy outcomes. Semen levels of ROS are positively correlated with body mass index. However, the acute energy restriction following bariatric surgery may paradoxically reduce sperm function, making it an unsuitable treatment for male infertility. No previous randomised controlled study has been performed investigating the effects of weight loss on sperm function and semen ROS in men with obesity and infertility. We hypothesized that milder weight loss through energy restriction could be a novel treatment to reduce semen ROS and improve sperm function in men with obesity and oligospermia. OBJECTIVE: Determine effects of a formula low energy diet (LED) on semen parameters and ROS in men with obesity and oligospermia. METHODS: Thirty-six men with obesity and oligospermia participated in a 16-week randomised, controlled study. After 2-weeks of baseline observation, all men were randomised to either LED (∼800kcal/day) or a control intervention of generalised healthy eating advice lasting 16-weeks; WHO semen analysis, semen ROS, metabolic parameters and reproductive hormones were monitored throughout the study. Semen ROS was measured in relative light years/sec/million sperm (RLU/s/mill) using an in-house, validated chemiluminescent luminol-based assay. RESULTS: At baseline, men with obesity and oligospermia had significantly elevated semen ROS levels when compared with the reference range generated from healthy men with normal BMI (median (inter-quartile range) ROS in RLU/s/mill: <3.8, healthy men; 60.3(113.1), control at baseline; 82.1(100.6) LED). Participants on the LED lost 9-fold more weight compared with control intervention (weight ± SD in kg: -1.5±4.3, control; -14.3±4.5, LED, p<0.0001). After 16 weeks, median semen ROS was reduced 12-fold greater in the LED versus control group (change in ROS vs. baseline in RLU/s/mill: -0.2(61.9), control; -6.0(137.5), LED; p<0.05). Total and progressive motility, and total motile count increased in the LED group versus the control intervention, but these changes were non-significant. CONCLUSIONS: This is the first randomised controlled study investigating effects of dietary weight loss on spermatogenesis in men with obesity and oligospermia. Our study provides proof-of-concept, and that weight loss could be used therapeutically in men with obesity and infertility, to reduce seminal ROS which is associated with increased sperm DNA damage. These data have important potential implications for management of couples with male infertility. Larger studies are needed to investigate whether weight loss is sufficient to improve pregnancy outcomes in couples affected by male infertility due to obesity. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.