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

Kai-Lun Hu, Kwanghann Gan, Rui Wang, Wentao Li, Qiongfang Wu, Beihong Zheng, Libo Zou, Su Zhang, Yifeng Liu, Yiqing Wu, Ruixue Chen, Wushuang Cao, Shuo Yang, Fen-Ting Liu, Lifeng Tian, Han Zeng, Huiling Xu, Shumin Qiu, Lihua Yang, Xiao Chen, Xiaoqin Pan, Xiaoyun Wu, Ben W Mol, Rong Li, Dan Zhang, Kai-Lun Hu, Kwanghann Gan, Rui Wang, Wentao Li, Qiongfang Wu, Beihong Zheng, Libo Zou, Su Zhang, Yifeng Liu, Yiqing Wu, Ruixue Chen, Wushuang Cao, Shuo Yang, Fen-Ting Liu, Lifeng Tian, Han Zeng, Huiling Xu, Shumin Qiu, Lihua Yang, Xiao Chen, Xiaoqin Pan, Xiaoyun Wu, Ben W Mol, Rong Li, Dan Zhang

Abstract

Introduction: Polycystic 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 analysis: We 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 dissemination: This 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 number: NCT04082650.

Keywords: maternal medicine; nutritional support; reproductive medicine; subfertility.

Conflict of interest statement

Competing interests: This trial is partly funded by Sinopharm Xingsha Pharmaceuticals (Xiamen) Co Ltd, which is the manufacturer of vitamin D. The funder has no role in the trial design, trial conduct, data collection, data analysis or manuscript preparation. All authors report no conflict of interest.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of recruitment. IVF, in vitro fertilisation; PCOS, polycystic ovary syndrome.
Figure 2
Figure 2
Study visits. ET, embryo transfer; FFQ, food frequency questionnaire; IVF, in vitro fertilisation; OHSS, ovarian hyperstimulation syndrome; SEQ, sunshine exposure questionnaire.

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