The Effect of VitC on IVF Outcome of DOR Patients

Not Applicable

Recruiting

• Conditions: Diminished Ovarian Reserve; IVF Outcomes

• Registration Number: NCT06794047
• Lead Sponsor: Peking University Third Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-20
• Study First Posted: 2025-01-27
• Study Start: 2025-03-17
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-11
• Last Update Posted: 2025-06-17
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Live birth rate	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%.

Secondary Outcome Measures

Name	Time	Method
Ongoing pregnancy	12 weeks after embryo transfer.	Presence of at least one gestational sac with fetal heartbeat confirmed by transvaginal ultrasound at 12 weeks after embryo transfer.
Total fertilization failure	Day 1 post-retrieval	No oocytes in the current treatment cycle show 2PN after fertilization or injection.
Number of usable embryos	On Day 3 post-retrieval	On Day 3 post-retrieval, embryos with ≥4 cells and ≤30% fragmentation are considered usable.
Number of implanted embryos	28-30 days after embryo transfer.	The number of gestational sacs (including intrauterine and ectopic) detected by transvaginal ultrasound 28-30 days after embryo transfer.
Ectopic pregnancy	1 year after oocyte retrieval following embryo transfer	A pregnancy occurring outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology.
Miscarriage	1 year after oocyte retrieval following embryo transfer	Spontaneous loss of an intrauterine pregnancy before 20 weeks of gestation. This should occur after ultrasound confirmation of a viable pregnancy.
Stillbirth	1 year after oocyte retrieval following embryo transfer	Fetal death occurring after 20 weeks of gestation, before complete expulsion or extraction. Death is determined by the absence of breathing or other signs of life (e.g., heartbeat, umbilical cord pulsation, or definite voluntary movement) after delivery.
Termination of pregnancy	1 year after oocyte retrieval following embryo transfer	Medical, surgical, or other artificial termination of an intrauterine pregnancy (including fetal reduction procedures).
Moderate or severe ovarian hyperstimulation syndrome (OHSS)	1 year after oocyte retrieval following embryo transfer	OHSS is primarily characterized by cystic enlargement of the ovaries, increased vascular permeability, third-space fluid accumulation (resulting in ascites and pleural effusion), and localized or generalized edema.)
Pregnancy complications	1 year after oocyte retrieval following embryo transfer	Including gestational diabetes mellitus, hypertensive disorders of pregnancy, antepartum hemorrhage, etc.
Gestational age	1 year after oocyte retrieval following embryo transfer	The number of weeks from fertilization to delivery, plus 14 days.
Preterm birth	1 year after oocyte retrieval following embryo transfer	Birth occurring before 37 weeks of gestation (i.e., fewer than 259 days of pregnancy).
Birth weight	1 year after oocyte retrieval following embryo transfer	The weight of the newborn at birth. Abnormal birth weight includes: Low birth weight (LBW): \<2,500 g Very low birth weight (VLBW): \<1,500 g High birth weight (macrosomia): \>4,000 g Very high birth weight: \>4,500 g
Large for gestational age (LGA)	1 year after oocyte retrieval following embryo transfer	Newborns with birth weight above the 90th percentile for their gestational age and sex.
Small for gestational age (SGA)	1 year after oocyte retrieval following embryo transfer	Newborns with birth weight below the 10th percentile for their gestational age and sex.
Neonatal death	1 year after oocyte retrieval following embryo transfer	Death of a live-born infant within 28 days after birth. This can be further categorized as: Early neonatal death: Death occurring within the first 7 days of life. Late neonatal death: Death occurring between 8 and 28 days of life.
Birth defect	1 year after oocyte retrieval following embryo transfer	Structural, functional, or genetic abnormalities occurring during pregnancy, which may be identified prenatally, at birth, or postnatally, and may be life-threatening or fatal. Major congenital anomalies should be reported as infants with at least one major congenital anomaly detected. If a major birth defect is identified in a multiple pregnancy, it should be explicitly reported.
Possible Vitamin C Side Effects-Abdominal Pain and Diarrhea:	1 year	A single high dose (5-10 g) of vitamin C may cause transient osmotic diarrhea and/or abdominal bloating. However, the human body has a high tolerance, and even such high doses are generally safe. Typically, these symptoms gradually improve or disappear after continued use.
Possible Vitamin C side effect--Hyperuricemia	1 year	Hyperuricemia: Vitamin C can be partially metabolized into oxalate and dose-dependently increase oxalate levels in urine. High doses of vitamin C may temporarily increase uric acid excretion, while high-dose intravenous administration may stimulate polyuria. Therefore, the daily recommended dose of vitamin C should not exceed 1 gram. Urine routine tests will be conducted during follow-up.
Possible Vitamin C side effect--Kidney stones	1 year	Some studies have found that high-dose oral vitamin C significantly increases the risk of kidney stone formation in men by 41%. Additionally, long-term high concentrations of oxalate in urine may contribute to stone formation. Thus, high-dose vitamin C supplementation in at-risk populations may lead to urinary tract stones, as self-reported by participants.
Possible Vitamin C side effect--Hemolysis	1 year	Intravenous or high-dose oral vitamin C may induce hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and worsen hemolysis in those with paroxysmal nocturnal hemoglobinuria. If such symptoms occur, vitamin C should be discontinued immediately, medical attention sought, and researchers contacted.
Clinical pregnancy rate	28-30 days after embryo transfer	Presence of at least one gestational sac (including intrauterine and ectopic) confirmed by transvaginal ultrasound 28-30 days after embryo transfer; includes singleton pregnancy rate and twin pregnancy rate (twin and multiple pregnancy rates should be reported along with pregnancy loss rate)
Cumulative live birth rate	1 year after oocyte retrieval following embryo transfer	Live births within 1 year after oocyte retrieval following embryo transfer; calculated as: (Final number of live births / Number of randomized participants) × 100%
Singleton live birth rate	1year after oocyte retrieval following embryo transfer	(Number of singleton live births / Number of randomized participants) × 100%
Twin live birth rate	1 year after oocyte retrieval following embryo transfer	(Number of women with twin live births / Number of randomized participants) × 100%
Time to pregnancy leading to live birth	1 year after oocyte retrieval following embryo transfer	or participants who achieved live birth, the time from intervention initiation to clinically confirmed pregnancy (confirmed by ultrasound 30 days after transfer). Survival analysis will be used to compare between intervention and control groups.
Number of oocytes retrieved	3 to 12 months from enrollment	Number of oocytes retrieved
Number of normally fertilized oocytes	Day 1 post-retrieval	On Day 1 post-retrieval, oocytes with two pronuclei (2PN) are counted as normally fertilized.
Number of high-quality embryos	On Day 3 post-retrieval	On Day 3 post-retrieval, 2PN-derived embryos with ≥6 cells and ≤10% fragmentation are classified as high-quality.
Vitamin C level after supplementation	3 months to 1 year

Trial Locations

Locations (6)

Beijing Obstetrics and Gynecology Hospital,Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking university third hospital; 🇨🇳 Beijing, Beijing, China

The second hospital of Hebei Medical University; 🇨🇳 Shijia Zhuang, Hebei, China

General Hospital of Ningxia Medical University; 🇨🇳 Yinchuan, Ningxia, China

Tang Du Hospital; 🇨🇳 Xi'an, Shanxi, China

Peking University Shenzhen Hospital; 🇨🇳 Shenzhen, Shenzhen, China