Efficacy of vitamin D supplementation and metformin compared to metformin alone in infertile females with polycystic ovary syndrome: a randomized open label trial.

Abstract Background: WHO has declared Infertility as the fifth-highest serious global disability with prevalence of approximately 22% in Pakistan; 80% due to polycystic ovarian syndrome (PCOS) . PCOS is characterized by “the presence of any two out of three criteria, that is oligo and/or anovulation, excess androgen activity and/or polycystic ovarian morphology on ultrasound”. Vitamin D deficiency (VDD) [serum 25(OH) D <20 ng/ml ] is vital for female health and becoming public health problem even in sun-drenched cities. With high prevalence (58%) of VDD in Pakistani PCOS . The hypothesis: “ VD supplementation can improve fertility by correcting in IR, ovulatory dysfunction, endometrial thickness and hyperandrogenism in primary infertile PCOS patients of our population”. We aim to evaluate impact of oral VD supplementation on fertility potential of VDD PCOS (VD <20 ng/ml) in a 2-years randomized clinical trial ; Group-1 VDD control PCOS (n=100) and Group-2 VDD intervention group (n=100) . Group-1 will receive 1.5 g/day metformin therapy for 24 weeks. Group-2 will be given 50,000 I.U of VD once weekly for 8 weeks, followed by 50,000 I.U once every fortnight from 9- 24 weeks plus metformin therapy. Impact will be assessed by comparing trans-vaginal ultrasound (TVS; Day 12) at the start with TVS at end point (24 weeks) to observe change in dominant follicle size (≥14 mm) and endometrial thickness (≥8 mm). Discussion: The proposed interventions will help to evaluate the impact of vitamin D supplementation on follicular maturation and endometrial thickness and PCOS parameters including lipid index and insulin resistance. Trial registration: ClinicalTrials.gov, NCT03989778