Clinical trial NCT06794047: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diminished Ovarian Reserve
IVF Outcomes
Keywords: vitamin C
IVF outcomes
livebirth
diminished ovarian reserve
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Obstetrics and Gynecology Hospital
name: Peking University Shenzhen Hospital
name: Tang-Du Hospital
name: General Hospital of Ningxia Medical University
name: The Second Hospital of Hebei Medical University
First posted: 2025-01-27
Enrollment: 1100
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Live birth rate
timeFrame: 1 year after oocyte retrieval following embryo transfer
Secondary outcomes:
measure: Cumulative live birth rate
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Singleton live birth rate
timeFrame: 1year after oocyte retrieval following embryo transfer
measure: Twin live birth rate
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Clinical pregnancy rate
timeFrame: 28-30 days after embryo transfer
measure: Ongoing pregnancy
timeFrame: 12 weeks after embryo transfer.
measure: Time to pregnancy leading to live birth
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Number of oocytes retrieved
timeFrame: 3 to 12 months from enrollment
measure: Number of normally fertilized oocytes
timeFrame: Day 1 post-retrieval
measure: Total fertilization failure
timeFrame: Day 1 post-retrieval
measure: Number of usable embryos
timeFrame: On Day 3 post-retrieval
measure: Number of high-quality embryos
timeFrame: On Day 3 post-retrieval
measure: Number of implanted embryos
timeFrame: 28-30 days after embryo transfer.
measure: Ectopic pregnancy
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Miscarriage
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Stillbirth
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Termination of pregnancy
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Moderate or severe ovarian hyperstimulation syndrome (OHSS)
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Pregnancy complications
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Gestational age
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Preterm birth
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Birth weight
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Large for gestational age (LGA)
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Small for gestational age (SGA)
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Neonatal death
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Birth defect
timeFrame: 1 year after oocyte retrieval following embryo transfer
measure: Possible Vitamin C Side Effects-Abdominal Pain and Diarrhea:
timeFrame: 1 year
measure: Possible Vitamin C side effect--Hyperuricemia
timeFrame: 1 year
measure: Possible Vitamin C side effect--Kidney stones
timeFrame: 1 year
measure: Possible Vitamin C side effect--Hemolysis
timeFrame: 1 year
measure: Vitamin C level after supplementation
timeFrame: 3 months to 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking university third hospital
state: Beijing
city: Shijia Zhuang
country: China
facility: The second hospital of Hebei Medical University
state: Hebei
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Xi'an
country: China
facility: Tang Du Hospital
state: Shanxi
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Shenzhen
Study officials:
References: