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.
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%.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
876
Peking University Third Hospital
Beijing, Beijing Municipality, China
Women's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Number of Participants with live birth
The primary outcome is live birth after the first embryo transfer. Live birth is defined as the delivery of at least one baby after 24 weeks of gestation that exhibits any sign of life.
Time frame: 1 day after delivery
Number of Participants with Cumulative live birth
Cumulative live birth: defined as live birth resulting from pregnancies that occur within 6 months after randomization.
Time frame: 6 months after randomization of the last participant
Number of Participants with Clinical pregnancy
Clinical pregnancy: defined as at least one gestational sac on ultrasound at around 7 weeks' gestation with the detection of heart beat activity after the completion of the first embryo transfer;
Time frame: 4 weeks after embryo transfer
birth weight
Weight of newborns at delivery.
Time frame: The day of delivery
Number of Participants with miscarriage
miscarriage was defined as a positive pregnancy test but no detectable heart rate before 24 weeks' gestation after the completion of the first transfer;
Time frame: 24 gestational weeks in maximum
Number of Participants with Ongoing pregnancy
defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond after the completion of the first transfer
Time frame: at 12 weeks' gestation
Number of Participants with Biochemical pregnancy
defined with a positive pregnancy test
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Time frame: 2 weeks after embryo transfer
Number of Participants with Ectopic pregnancy
defined as embryo implanted at any site other than the endometrial lining of the uterus cavity after the completion of the first transfer
Time frame: 4 weeks after embryo transfer
Number of Participants with Ovarian hyperstimulation syndrome
defined according to the Golan criteria. Moderate OHSS is diagnosed by the presence of ascites on ultrasonography in addition to abdominal distension and discomfort with or without nausea, vomiting and/or diarrhea. Severe OHSS is diagnosed when there is clinical evidence of ascites and/or hydrothorax or breathing difficulties with or without hemoconcentration, coagulation abnormalities and diminished renal function.
Time frame: From the day of oocyte retrieval to two weeks after embryo transfer
Number of available embryos for transfer
non
Time frame: 5 days after oocyte retrieval
Number of Participants with Pre-eclampsia
defined as the development of gestational hypertension with proteinuria (≥300 mg/24-hour urine collection or 30 mg/dL in single urine sample) of new onset after 20 weeks of gestation after the completion of the first transfer
Time frame: 20 weeks of gestation till delivery
Number of Participants with Gestational hypertension
defined as the development of blood pressure greater than 140/90 mmHg after pregnancy without proteinuria or other signs of preeclampsia after the completion of the first transfer;
Time frame: 20 weeks of gestation till delivery
Number of Participants with Premature rupture of membrane
PROM was defined as rupture of the amniotic membranes before the onset of labor including PROM at term and preterm PROM.
Time frame: The day of delivery
Number of Participants with Postpartum hemorrhage
defined as the loss of 500 ml of blood or more after completion of the third stage of labor after the completion of the first transfer
Time frame: 1 day after delivery
Number of Participants with Preterm delivery
Defined as delivery of a fetus at less than 37 and more than 28 weeks' gestational age after the completion of the first transfer
Time frame: 1 day after delivery
Number of Participants with Gestational diabetes mellitus
defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy as determined from the diagnosis in the obstetrical medical record
Time frame: Up to ten months once the participants get pregnancy
Number of Participants with Placenta previa
defined as a placenta that is implanted over or very close to the internal cervical orifice
Time frame: after 24 weeks of gestation
Number of Participants with Stillbirth
defined as the absence of signs of life at or after birth after the completion of the first transfer
Time frame: 1 day after delivery
Apgar score
non
Time frame: 1 minute or 5 minutes after delivery
Serum Vitamin D binding protein, glucose, insulin, Calcium ion concentration
non
Time frame: The day of oocyte retrieval
Serum vitamin levels
Serum vitamin levels at the triggering day
Time frame: One day before oocyte retrieval