Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial

Abstract

IntroductionPolycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS.Methods and analysisWe plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%).Ethics and disseminationThis study has been approved by the Ethics Committee in Women’s Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal.Trial registration numberNCT04082650.

Effect of Vitamin D Supplementation on In Vitro Fertilization Outcomes: A Trial Sequential Meta-Analysis of 5 Randomized Controlled Trials

“…Of which, chemical pregnancy was defined as serum level of human chorionic gonadotropin beta subunit (β-hCG) >50 IU/L at 14 days after embryo transfer ( 28 ), and clinical pregnancy was defined as the presence of at least one intrauterine gestational sac with viable fetus ( 36 ). Among 4 secondary outcomes, good quality embryos were defined as the presence of 6 to 8 blastomeres with even size and <25% fragmentation ( 27 ), fertilization rate was defined as the result of the number of 2PN observed divided by the number of injected oocytes ( 27 ), ongoing pregnancy was defined as pregnancy with detectable heart rate at more than 12 weeks gestation ( 37 ), and miscarriage was defined as a positive pregnancy test but no detectable heart rate before 24 weeks gestation ( 37 ).…”

Beyond the Umbrella: A Systematic Review of the Interventions for Prevention of and Reduction in the Incidence and Severity of Ovarian Hyperstimulation Syndrome in Patients Who Undergo In Vitro Fertilization Treatments

“…A large multicenter randomized, double-blinded, placebo-controlled trial, evaluating the effectiveness of oral capsules of 4000 IU vitamin D per day given as a pretreatment and cotreatment (from 12 weeks before up to the day of triggering) in IVF patients with PCOS is in progress [120]. The incidence of moderate and severe OHSS will be reported as the secondary outcome [120], and the results are awaited with interest.…”

Insights into the perspective correlation between vitamin D and regulation of hormones: sex hormones and prolactin

“…The study began in July 2020, with a recruitment period of 18 months (the last participant is planned to be recruited in December 2020). The results of this study will be essential in revealing the exact effect of VD on fertility and IVF success [65].…”