L26/P-775 Impact of semaglutide on fertility and reproductive outcomes in female mice

Abstract Study question Does semaglutide have a direct effect on female fertility in a murine model? Summary answer Semaglutide directly reduces the number of retrieved oocytes in mice and this inhibitory effect is reversed following a wash-out period. What is known already Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is now widely prescribed for the management of obesity and type 2 diabetes.The receptors are expressed throughout the hypothalamic-pituitary-ovarian axis. While preclinical studies demonstrate that GLP-1RAs can reverse polycystic ovary syndrome (PCOS) morphology and improve reproductive outcomes, existing research has predominantly focused on PCOS-specific models. Consequently, there is a significant data gap regarding the impact of these drugs on non-PCOS obesity models, despite a rising number of clinical reports of unexpected pregnancies in women using GLP-1RAs for weight management. Study design, size, duration This was a prospective experimental study using a murine model. Female C57BL/6J mice (8 weeks old) were utilized across three experimental phases. The study compared short-term treatment effects (14 days), recovery effects following a wash-out period (7 days), and long-term weight-loss effects in a diet-induced obesity (DIO) model (a diet-induced obesity (DIO) model (16-week induction followed by 28 days of treatment and 7 days wash-out) Participants/materials, setting, methods This prospective murine study evaluated semaglutide’s reproductive impact across three phases: acute treatment (14-day), reversibility (7-day wash-out), and weight loss in diet-induced obesity models(16-week induction followed by 28 days of treatment and 7 days wash-out).Natural pregnancy outcomes, IVF parameters, and ovarian molecular mechanisms were analyzed to evaluate reproductive health and the impact of weight loss across lean and obese cohorts. Main results and the role of chance Acute 14-day semaglutide administration initially reduced oocyte retrieval numbers; however, this effect was fully reversed after a 7-day washout period. Furthermore, 28-day semaglutide treatment significantly improved natural pregnancy outcomes and IVF parameters, demonstrating efficacy comparable to the calorie-restricted group. Limitations, reasons for caution Results from this murine model may not fully translate to human physiology. Additionally, the study focused on short-term treatment and recovery intervals; long-term reproductive outcomes and the impact of chronic semaglutide exposure on subsequent generations remain to be established. Wider implications of the findings These findings offer critical guidance for semaglutide administration in women of reproductive age. The data suggest that weight-loss benefits may significantly improve fertility parameters, provided that appropriate treatment durations and washout periods are implemented to manage transient effects on oocyte quantity. Trial registration number No