Clinical trial NCT04082650: Vitamin D and Pregnancy Outcome in PCOS Patients
Official title: Vitamin D Supplementation Prior to in Vitro Fertilization in Women With Polycystic Ovary Syndrome: a Protocol of a Multicenter Randomised Double-blind Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
in Vitro Fertilization
Keywords: Polycystic Ovary Syndrome
in vitro fertilization
Vitamin D
randomized trial
Lead sponsor: Women's Hospital School Of Medicine Zhejiang University
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 876
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter double-blinded placebo-controlled randomised trial aims to evaluate the effectiveness of vitamin D supplementation prior to IVF on the live birth rate in women with PCOS. Women with PCOS scheduled for IVF will be enrolled. Eligible participants will be randomised 1:1 to receive oral capsules of 4000IU vitamin D per day or placebo for around 12 weeks until the day of triggering.

Detailed description: Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women with a child-bearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates in these women. However, evidence regarding the effectiveness of vitamin D treatment in women with PCOS is inconclusive. This multicenter double-blinded placebo-controlled randomised trial aims to evaluate the effectiveness of vitamin D supplementation prior to IVF on the live birth rate in women with PCOS.

The investigators plan to enroll women with PCOS scheduled for IVF. Eligible participants will be randomised 1:1 to receive oral capsules of 4000IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out following a routine method in each center. Women will be followed up until six months after randomisation for those who fail to get pregnant after the completion of the first embryo transfer or delivery for those who get pregnant after the first embryo transfer. The primary outcome is live birth after the first embryo transfer. Primary analysis will be by intention-to-treat analysis. The investigators plan to recruit 860 women to demonstrate women treated with vitamin D have a higher live birth rate than those treated with placebo (48% versus 38%), accounting for 10% loss to follow-up with a significance level at 0.05 and a power of 80%.

Eligibility criteria: Inclusion criteria

1. Women aged 20 to 42 years old;
2. Diagnosed with PCOS (Rotterdam Criteria);
3. Scheduled for IVF;
4. Written informed consent.

Exclusion criteria

1. Women who had three or more failed IVF cycles;
2. Women scheduled for preimplantation genetic testing;
3. Known Vitamin D allergy;
4. Women with a history of chronic absorption syndrome or bile dysplasia, or parathyroid dysfunction, or kidney stones, or blood Calcium ion concentration greater than 2.6mmol/L (normal value 2.25 - 2.75mmol/L (9 to 11mg/dl), or hyperphosphataemia (1.61mmol/L), or metabolic-related bone disease, or chronic diseases that may cause bone abnormalities (liver and kidney insufficiency);
5. Women receiving treatments for tuberculosis, convulsions, and epilepsy because medications treating these diseases may affect the metabolism of vitamin D.
6. Women undergoing an IVF treatment with donor oocytes.

Primary outcomes:
measure: Number of Participants with live birth
timeFrame: 1 day after delivery
Secondary outcomes:
measure: Number of Participants with Cumulative live birth
timeFrame: 6 months after randomization of the last participant
measure: Number of Participants with Clinical pregnancy
timeFrame: 4 weeks after embryo transfer
measure: birth weight
timeFrame: The day of delivery
measure: Number of Participants with miscarriage
timeFrame: 24 gestational weeks in maximum
measure: Number of Participants with Ongoing pregnancy
timeFrame: at 12 weeks' gestation
measure: Number of Participants with Biochemical pregnancy
timeFrame: 2 weeks after embryo transfer
measure: Number of Participants with Ectopic pregnancy
timeFrame: 4 weeks after embryo transfer
measure: Number of Participants with Ovarian hyperstimulation syndrome
timeFrame: From the day of oocyte retrieval to two weeks after embryo transfer
measure: Number of available embryos for transfer
timeFrame: 5 days after oocyte retrieval
measure: Number of Participants with Pre-eclampsia
timeFrame: 20 weeks of gestation till delivery
measure: Number of Participants with Gestational hypertension
timeFrame: 20 weeks of gestation till delivery
measure: Number of Participants with Premature rupture of membrane
timeFrame: The day of delivery
measure: Number of Participants with Postpartum hemorrhage
timeFrame: 1 day after delivery
measure: Number of Participants with Preterm delivery
timeFrame: 1 day after delivery
measure: Number of Participants with Gestational diabetes mellitus
timeFrame: Up to ten months once the participants get pregnancy
measure: Number of Participants with Placenta previa
timeFrame: after 24 weeks of gestation
measure: Number of Participants with Stillbirth
timeFrame: 1 day after delivery
measure: Apgar score
timeFrame: 1 minute or 5 minutes after delivery
measure: Serum Vitamin D binding protein, glucose, insulin, Calcium ion concentration
timeFrame: The day of oocyte retrieval
measure: Serum vitamin levels
timeFrame: One day before oocyte retrieval
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Hangzhou
country: China
facility: Women's Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Women's Hospital School Of Medicine Zhejiang University
name: Dan Zhang, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hu KL, Gan K, Wang R, Li W, Wu Q, Zheng B, Zou L, Zhang S, Liu Y, Wu Y, Chen R, Cao W, Yang S, Liu FT, Tian L, Zeng H, Xu H, Qiu S, Yang L, Chen X, Pan X, Wu X, Mol BW, Li R, Zhang D. 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. BMJ Open. 2020 Dec 8;10(12):e041409. doi: 10.1136/bmjopen-2020-041409.