Vitamin D and Pregnancy Outcome in PCOS Patients

Sponsor

Women's Hospital School Of Medicine Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04082650

Collaborator

(none)

860

Enrollment

Locations

Arms

40.8

Anticipated Duration (Months)

430

Patients Per Site

10.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome in Vitro Fertilization	Drug: vitamin D Other: Placebo	N/A

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%.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

860 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Participants and most researchers will be unaware of the actual grouping. Only two researchers who are not involved in participant management or data analysis will be aware of the grouping. Vitamin D and placebo pills with identical package, size, colour and appearance will be used in this trial. In general, there should be no need to unblind the allocation. If urgent unbinding to participants is necessary, the allocation will be disclosed to the treating physician.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 15, 2020

Anticipated Primary Completion Date :

Feb 2, 2023

Anticipated Study Completion Date :

Mar 10, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D 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 4000IU per day Other Names: non
Placebo Comparator: Placebo Participants in the control group will be treated with equal amount of placebo tablets per day for the same duration.	Other: Placebo The same doses with vitamin D

Arm

Intervention/Treatment

Experimental: Vitamin D

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

4000IU per day

Other Names:

non

Placebo Comparator: Placebo

Participants in the control group will be treated with equal amount of placebo tablets per day for the same duration.

Other: Placebo

The same doses with vitamin D

Outcome Measures

Primary Outcome Measures

Number of Participants with live birth [1 day after delivery]
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.

Secondary Outcome Measures

Number of Participants with Cumulative live birth [6 months after randomization of the last participant]
Cumulative live birth: defined as live birth resulting from pregnancies that occur within 6 months after randomization.
Number of Participants with Clinical pregnancy [4 weeks after embryo transfer]
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;
birth weight [The day of delivery]
Weight of newborns at delivery.
Number of Participants with miscarriage [24 gestational weeks in maximum]
miscarriage was defined as a positive pregnancy test but no detectable heart rate before 24 weeks' gestation after the completion of the first transfer;
Number of Participants with Ongoing pregnancy [at 12 weeks' gestation]
defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond after the completion of the first transfer
Number of Participants with Biochemical pregnancy [2 weeks after embryo transfer]
defined with a positive pregnancy test
Number of Participants with Ectopic pregnancy [4 weeks after embryo transfer]
defined as embryo implanted at any site other than the endometrial lining of the uterus cavity after the completion of the first transfer
Number of Participants with Ovarian hyperstimulation syndrome [From the day of oocyte retrieval to two weeks after embryo transfer]
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.
Number of available embryos for transfer [5 days after oocyte retrieval]
non
Number of Participants with Pre-eclampsia [20 weeks of gestation till delivery]
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
Number of Participants with Gestational hypertension [20 weeks of gestation till delivery]
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;
Number of Participants with Premature rupture of membrane [The day of delivery]
PROM was defined as rupture of the amniotic membranes before the onset of labor including PROM at term and preterm PROM.
Number of Participants with Postpartum hemorrhage [1 day after delivery]
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
Number of Participants with Preterm delivery [1 day after 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
Number of Participants with Gestational diabetes mellitus [Up to ten months once the participants get pregnancy]
defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy as determined from the diagnosis in the obstetrical medical record
Number of Participants with Placenta previa [after 24 weeks of gestation]
defined as a placenta that is implanted over or very close to the internal cervical orifice
Number of Participants with Stillbirth [1 day after delivery]
defined as the absence of signs of life at or after birth after the completion of the first transfer
Apgar score [1 minute or 5 minutes after delivery]
non
Serum Vitamin D binding protein, glucose, insulin, Calcium ion concentration [The day of oocyte retrieval]
non
Serum vitamin levels [One day before oocyte retrieval]
Serum vitamin levels at the triggering day

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 42 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.