The Effect of VitC on IVF Outcome of DOR Patients

Official title

The Effect of Vitamin C Supplementation on Assisted Reproductive Pregnancy Outcomes in Patients With Diminished Ovarian Reserve: A Multicenter, Double-blind, Randomized Controlled Trial.

Overview

In the context of the accelerating aging population and the continuous decline in birth rates nationwide, delaying reproductive aging in women and protecting the fertility of women of childbearing age have become urgent issues and key demands that need to be addressed in the field of maternal and child health in China. The ovaries have reproductive and hormone secretion functions and are crucial throughout the female reproductive lifecycle. Women of childbearing age in China face a serious problem of diminished ovarian reserve (DOR), which can lead to infertility, failed in vitro fertilization (IVF) treatments, miscarriage, and other adverse pregnancy outcomes, severely affecting the safety of women and their offspring. For DOR patients who desire to conceive, failure to intervene and treat promptly can result in irreversible losses and impose a significant psychological burden on them. However, there are currently no clear and reliable interventions that can improve ovarian function and enhance fertility in women with DOR. Therefore, exploring new, safe, and patient-acceptable intervention strategies is urgently needed, as it may bring hope and light to women with DOR. Nutrient supplementation, especially vitamin supplementation, has received increasing attention in disease treatment due to its safety, bioavailability, and effectiveness. Previous studies have shown that vitamin C may play an important role in treating diminished ovarian reserve. However, its effects on ovarian function need to be validated in the population. Based on the above research background, this project will conduct a randomized, placebo-controlled, double-blind, multicenter trial. The study subjects will be DOR infertility patients undergoing IVF/ICSI treatment. The intervention group will receive oral vitamin C supplementation at a dosage of 500 mg per dose, twice a day; the control group will receive a placebo with the same dosage and method for at least three months. Patients will be followed up until delivery outcomes, comparing the IVF/ICSI treatment results between the vitamin C supplementation group and the placebo group. The primary endpoint of this clinical trial is the live birth rate of the IVF/ICSI treatment cycle. Secondary endpoints include indicators of improved ovarian reserve function, ovarian aging molecular clocks, IVF-embryo culture indicators, pregnancy rates, pregnancy complications, and neonatal conditions, thereby providing new clues and theoretical basis for clinical treatment plans for DOR patients.

Interventions

• Dietary supplement Vitamin C
  Vitamin C tablets, please instruct the patient to swallow with water, 500mg twice daily, morning and evening.
• Other Placebo
  Tablets with the same material, flavor, and appearance as the intervention group.

Primary outcome measures

• Live birth rate [Time frame: 1 year after oocyte retrieval following embryo transfer]

Secondary outcome measures (12)

• Cumulative live birth rate [Time frame: 1 year after oocyte retrieval following embryo transfer]
• Singleton live birth rate [Time frame: 1year after oocyte retrieval following embryo transfer]
• Twin live birth rate [Time frame: 1 year after oocyte retrieval following embryo transfer]
• Clinical pregnancy rate [Time frame: 28-30 days after embryo transfer]
• Ongoing pregnancy [Time frame: 12 weeks after embryo transfer.]
• Time to pregnancy leading to live birth [Time frame: 1 year after oocyte retrieval following embryo transfer]
• Number of oocytes retrieved [Time frame: 3 to 12 months from enrollment]
• Number of normally fertilized oocytes [Time frame: Day 1 post-retrieval]
• Total fertilization failure [Time frame: Day 1 post-retrieval]
• Number of usable embryos [Time frame: On Day 3 post-retrieval]
• Number of high-quality embryos [Time frame: On Day 3 post-retrieval]
• Number of implanted embryos [Time frame: 28-30 days after embryo transfer.]

Eligibility criteria

Definition of DOR: Currently, there is no internationally unified standard for DOR. According to the latest POSEIDON criteria for diminished ovarian reserve (DOR), serum AMH <1.20 ng/mL or bilateral antral follicle count (AFC) <5 is classified as DOR.

In this study, the participants are primarily DOR patients, with the following inclusion criteria:

• Infertile women undergoing their 1st or 2nd IVF treatment
• Diagnosed with DOR: POSEIDON criteria (AMH <1.2 ng/mL or bilateral AFC <5) BMI between 18.5-28.0 kg/m²
• Signed informed consent

Exclusion Criteria：Participants meeting any of the following criteria will be excluded from the trial:

• PGT (preimplantation genetic testing) candidates
• DOR caused by ovarian surgery, cancer radiotherapy/chemotherapy
• Other ovulation disorders (e.g., PCOS, Cushing's syndrome, non-classic congenital adrenal hyperplasia, hyperprolactinemia) or endometriosis (chocolate cysts)
• Severe thyroid disorders: Hyperthyroidism, Graves' disease, Hashimoto's thyroiditis
• Acute/chronic renal insufficiency, hemodialysis, or history of severe kidney impairment
• Infectious diseases: HIV, active hepatitis, metabolic acidosis, tuberculosis, etc.
• Severe autoimmune diseases (e.g., rheumatoid arthritis, lupus, Crohn's disease)
• Cardiovascular events within the past 3 months: Coronary artery disease/myocardial infarction/clinically significant congestive heart failure；Stroke/transient ischemic attack (TIA)；Deep vein thrombosis/pulmonary embolism；Poorly controlled hypertension (SBP ≥160 mmHg or DBP ≥90 mmHg)；Diagnosed diabetes mellitus；Coronary intervention (PCI) or coronary artery bypass grafting (CABG)；
• Neurological disorders (e.g., dementia,Alzheimer's, Parkinson's) or use of related medications
• Psychiatric disorders or use of antiepileptic/antidepressant drugs
• History of cancer or radiotherapy/chemotherapy
• Allergy to vitamin C
• Current high-dose vitamin C supplementation (>500 mg/day)
• Unwillingness to take the study-provided supplements
• Alcohol abuse, smoking, or drug addiction
• Participation in other clinical trials within the past month

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 6 centers

• Beijing Obstetrics and Gynecology Hospital,Capital Medical University — Beijing
• Peking university third hospital — Beijing
• The second hospital of Hebei Medical University — Shijiazhuang
• General Hospital of Ningxia Medical University — Yinchuan
• Tang Du Hospital — Xi’an
• Peking University Shenzhen Hospital — Shenzhen

Identifiers

NCT: NCT06794047 · M2024646 · No2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗