Vitamin D and Pregnancy Outcome in PCOS Patients

Study Overview
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Brief Summary
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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
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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%.

Official Title
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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

Conditions
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Polycystic Ovary Syndrome, in Vitro Fertilization

Intervention / Treatment
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* Drug: vitamin D
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Women aged 20 to 42 years old; Diagnosed with PCOS (Rotterdam Criteria); Scheduled for IVF; Written informed consent. Exclusion criteria Women who had three or more failed IVF cycles; Women scheduled for preimplantation genetic testing; Known Vitamin D allergy; 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); Women receiving treatments for tuberculosis, convulsions, and epilepsy because medications treating these diseases may affect the metabolism of vitamin D. Women undergoing an IVF treatment with donor oocytes.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>Participants in the intervention group will be treated with vitamin D 4000IU (800IU per pill, take five pills once each day) per day for around 12 weeks (till the triggering day). | Drug: vitamin D<br>* 4000IU per day<br>* Other names: non;|
| Placebo Comparator: Placebo<br>Participants in the control group will be treated with equal amount of placebo tablets per day for the same duration. | Other: Placebo<br>* The same doses with vitamin D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 day after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Cumulative live birth | Cumulative live birth: defined as live birth resulting from pregnancies that occur within 6 months after randomization. | 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; | 4 weeks after embryo transfer | 
| birth weight | Weight of newborns at delivery. | 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; | 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 | at 12 weeks' gestation | 
| Number of Participants with Biochemical pregnancy | defined with a positive pregnancy test | 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 | 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. | From the day of oocyte retrieval to two weeks after embryo transfer | 
| Number of available embryos for transfer | non | 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 | 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; | 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. | 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 | 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 | 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 | 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 | 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 | 1 day after delivery | 
| Apgar score | non | 1 minute or 5 minutes after delivery | 
| Serum Vitamin D binding protein, glucose, insulin, Calcium ion concentration | non | The day of oocyte retrieval | 
| Serum vitamin levels | Serum vitamin levels at the triggering day | One day before oocyte retrieval | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome, in vitro fertilization, Vitamin D, randomized trial