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.

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

We have decided not to share the IPD from this study due to concerns about participant privacy and confidentiality. Despite efforts to de-identify the data, there remains a risk of re-identification, which could compromise the privacy of the participants involved. Additionally, there are legal and ethical considerations that restrict the sharing of sensitive health information without explicit consent from the participants. Furthermore, the resources required to prepare and manage the data for external sharing are currently beyond our capacity. Therefore, to ensure the protection of our participants and comply with ethical standards, we have opted not to share the IPD at this time.

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.