The Effect of Vitamin C Supplementation on Assisted Reproductive Pregnancy Outcomes in Patients With Diminished Ovarian Reserve: A Multicenter, Double-blind, Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,100
- 试验地点
- 6
- 主要终点
- Live birth rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
During the entire implementation of the RCT, a double-blind design was employed for both the study subjects and researchers. Group allocation concealment was applied to study subjects, clinical practitioners involved in the RCT, outcome observers and assessors, and subsequent data analysts. The pharmaceutical company assigned numbers and labels to the drugs, and when study subjects were enrolled, they were assigned the corresponding drug number. The specific group corresponding to the number remained concealed from the project researchers, participants, and study subjects, with the blind data kept by independent personnel.
After the follow-up, independent personnel who maintained the blind data provided group information to the data analysts. The vitamin C and control groups were still represented as A and B, concealing the specific identities of the AB groups from the data analysts. After the data comparison between the two groups the unblinding of the AB groups was conducted.
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
Tablets with the same material, flavor, and appearance as the intervention group.
干预措施: Placebo (Other)
VitC
The women will intake the vitamin C twice a day, 500mg per time.
干预措施: Vitamin C (Dietary Supplement)
结局指标
主要结局
Live birth rate
时间窗: 1 year after oocyte retrieval following embryo transfer
The main outcome of this trial is the live birth resulting from a sustained pregnancy after the first embryo transfer within 6 months for patients undergoing fresh transfer cycles or frozen embryo cycles. Live birth rate (%) = Number of subjects with live births in each group / Total number of subjects in each group × 100%.
次要结局
- Miscarriage(1 year after oocyte retrieval following embryo transfer)
- Ongoing pregnancy(12 weeks after embryo transfer.)
- Clinical pregnancy rate(28-30 days after embryo transfer)
- Cumulative live birth rate(1 year after oocyte retrieval following embryo transfer)
- Singleton live birth rate(1year after oocyte retrieval following embryo transfer)
- Twin live birth rate(1 year after oocyte retrieval following embryo transfer)
- Time to pregnancy leading to live birth(1 year after oocyte retrieval following embryo transfer)
- Number of oocytes retrieved(3 to 12 months from enrollment)
- Number of normally fertilized oocytes(Day 1 post-retrieval)
- Total fertilization failure(Day 1 post-retrieval)
- Number of usable embryos(On Day 3 post-retrieval)
- Number of high-quality embryos(On Day 3 post-retrieval)
- Number of implanted embryos(28-30 days after embryo transfer.)
- Ectopic pregnancy(1 year after oocyte retrieval following embryo transfer)
- Stillbirth(1 year after oocyte retrieval following embryo transfer)
- Termination of pregnancy(1 year after oocyte retrieval following embryo transfer)
- Moderate or severe ovarian hyperstimulation syndrome (OHSS)(1 year after oocyte retrieval following embryo transfer)
- Pregnancy complications(1 year after oocyte retrieval following embryo transfer)
- Gestational age(1 year after oocyte retrieval following embryo transfer)
- Preterm birth(1 year after oocyte retrieval following embryo transfer)
- Birth weight(1 year after oocyte retrieval following embryo transfer)
- Large for gestational age (LGA)(1 year after oocyte retrieval following embryo transfer)
- Small for gestational age (SGA)(1 year after oocyte retrieval following embryo transfer)
- Neonatal death(1 year after oocyte retrieval following embryo transfer)
- Birth defect(1 year after oocyte retrieval following embryo transfer)
- Possible Vitamin C Side Effects-Abdominal Pain and Diarrhea:(1 year)
- Possible Vitamin C side effect--Hyperuricemia(1 year)
- Possible Vitamin C side effect--Kidney stones(1 year)
- Possible Vitamin C side effect--Hemolysis(1 year)
- Vitamin C level after supplementation(3 months to 1 year)
研究者
Jie Qiao
Professor
Peking University Third Hospital