Vitamin D and Pregnancy Outcome in PCOS Patients

Polycystic Ovary Syndrome Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04082650
• Other study ID #: VDPI
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2020
• Est. completion date: March 10, 2024

Study information

• Verified date: July 2022
• Source: Women's Hospital School Of Medicine Zhejiang University
• Contact: Dan Zhang, M.D. Ph.D.
• Phone: 86-0571-87061501-1008
• Email: zhangdan[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 860
• Est. completion date: March 10, 2024
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 42 Years

Eligibility

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.

Related Conditions & MeSH terms

• in Vitro Fertilization
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• vitamin D
4000IU per day

Other:
• Placebo
The same doses with vitamin D

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing
China	Women's Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Women's Hospital School Of Medicine Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	birth weight	Weight of newborns at delivery.	The day of delivery
Secondary	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
Secondary	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
Secondary	Number of Participants with Biochemical pregnancy	defined with a positive pregnancy test	2 weeks after embryo transfer
Secondary	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
Secondary	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
Secondary	Number of available embryos for transfer	non	5 days after oocyte retrieval
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apgar score	non	1 minute or 5 minutes after delivery
Secondary	Serum Vitamin D binding protein, glucose, insulin, Calcium ion concentration	non	The day of oocyte retrieval
Secondary	Serum vitamin levels	Serum vitamin levels at the triggering day	One day before oocyte retrieval