Comparison of live birth rates between calorie-restricted diet and metformin prior to ovulation induction therapy in women with polycystic ovary syndrome and overweight/obesity: a protocol for a multicenter, randomized comparative effectiveness trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) significantly impairs physical and mental health, quality of life, and fertility in women of reproductive age. Strategies to enhance fertility in PCOS have been prioritised in International Guidelines. Whilst Guidelines recommend Letrozole in first line ovulation induction (OI), therapeutic interventions to optimise endocrine and metabolic PCOS features prior to OI have not been adequately researched despite potential to improve live birth and pregnancy outcomes. Whilst both a calorie-restricted (CR) diet and metformin interventions may offer benefits in the context, evidence is limited including for live birth rates, and pregnancy outcomes. Therefore, this study will aim aims to compare the effects of a CR diet versus metformin on live birth, endocrine, reproductive, and metabolic parameters as well as pregnancy outcomes in women with PCOS and overweight/obesity. METHOD: This multicenter, randomized (1:1) comparative effectiveness trial will evaluate and compare the effects of a CR diet versus metformin, administered for 12 weeks prior to OI, on live birth, endocrine, metabolic, reproductive, and pregnancy outcomes in women with PCOS and overweight/obesity. The primary analysis will follow the intention-to-treat principle, including all participants who underwent randomization. DISCUSSION: This trial investigates the comparative efficacy of a CR diet versus metformin over a 12-week period prior to OI therapy in women with PCOS and overweight/obesity. Early therapeutic intervention holds significant potential to disrupt the pathophysiological cycle characterized by hyperandrogenism, excessive adiposity, and insulin resistance for improving fertility and pregnancy outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT06049186.