Vitamin D supplementation before in vitro fertilisation in women with polycystic ovary syndrome: multicentre, double blind, placebo controlled, randomised clinical trial

多囊卵巢综合征女性体外受精前补充维生素D:一项多中心、双盲、安慰剂对照、随机临床试验

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Abstract

OBJECTIVE: To evaluate whether vitamin D supplementation improves live birth rates in women with polycystic ovary syndrome undergoing in vitro fertilisation. DESIGN: Multicentre, double blind, placebo controlled, randomised clinical trial. SETTING: 24 fertility centres in China. PARTICIPANTS: 876 participants with polycystic ovary syndrome undergoing in vitro fertilisation. INTERVENTIONS: Participants were randomised (1:1) to receive vitamin D 4000 IU/day or placebo before in vitro fertilisation for up to 90 days until the trigger day. MAIN OUTCOMES MEASURES: The primary outcome was live birth after the first embryo transfer. Secondary outcomes included serum 25-hydroxyvitamin D (25-OHD) levels on trigger day, pregnancy outcomes, fertility outcomes, and adverse events including severe ovarian hyperstimulation syndrome. RESULTS: Of 876 participants randomised, 865 were included in the modified intention-to-treat analysis, with 435 in the vitamin D group and 430 in the placebo group. Baseline mean serum 25-OHD levels were 16.5±7.2 and 16.1±6.7 ng/mL in the vitamin D and placebo groups, respectively. On the day of triggering, the serum 25-OHD level was significantly higher in the vitamin D group than in the placebo group (32.3±11.2 v 18.2±7.6 ng/mL, adjusted mean difference 13.6, 95% confidence interval 10.9 to 16.3). 226 (52.0%) live births occurred in the vitamin D group and 216 (50.2%) in the placebo group (adjusted risk ratio 1.03, 95% confidence interval 0.91 to 1.18). Severe ovarian hyperstimulation syndrome occurred in three and six participants in the vitamin D and placebo groups, respectively (adjusted risk difference -0.7%, 95% confidence interval -2.0% to 0.6%). CONCLUSIONS: Although vitamin D supplementation (4000 IU/day) for up to 90 days increases serum 25-OHD levels, this does not translate to improved live birth rates after the first transfer for patients with polycystic ovary syndrome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04082650.

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