Nicotinamide Riboside vs. Vitamin E for Enhancing Fertility in Advanced Maternal Age: A Randomized Parallel Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Number of Day 3 embryos
研究概览
简要总结
This randomized controlled trial enrolled women of advanced maternal age (≥35 years) undergoing ART, who were allocated to an intervention group (oral nicotinamide riboside, NR) or a control group (oral vitamin E, VitE) for a 2-month pre-ART intervention. The study systematically evaluated NR's regulatory effects on ovarian function and ART outcomes by measuring NAD+ levels in ovarian granulosa cells (GCs) and peripheral blood mononuclear cells (PBMCs), anti-Müllerian hormone (AMH) concentrations.
详细描述
Patients received daily oral supplementation of either nicotinamide riboside (NR, 600 mg/day) or vitamin E (200 mg/day) for two consecutive months, initiated on day 2 of the menstrual cycle. Participants were enrolled if they planned to undergo in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotropin-releasing hormone (GnRH) antagonist protocol following the intervention period.
Biological Samples
Peripheral blood mononuclear cells (PBMC) were isolated from venous blood.
Follicular fluid containing granulosa cells and discarded oocytes were collected during routine oocyte retrieval procedures.
Hormonal and Ovarian Assessments
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)
入排标准
- 年龄范围
- 35 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Infertile women aged between 35 and 42 years;
- •0.1 ng/mL <= AMH <= 1.1 ng/ml;
- •Pregnancy aids who plan to perform in vitro fertilization and embryo transfer (antagonist program);
- •Bilateral ovaries are present;
- •Patients who voluntarily signed the informed consent and agreed to be followed up according to the requirements of the study protocol.
排除标准
- •Adenomyosis and uterine fibroids compression of uterine uterine line;
- •Untreated bilateral hydrosalpinx;
- •Uncured endometrial disease;
- •Any pregnancy occurred within 3 months before screening;
- •Patients with clinically significant abnormal cervical examination results within 3 months before screening;
- •Use of fertility regulators (such as clomiphene citrate, GnRH, metformin or oral contraceptives) within 1 month before randomization;
- •Use hormone drugs within 1 month before randomization;
- •Patients with acute infection of urinary and reproductive system;
- •Patients with major systemic diseases, endocrine or metabolic abnormalities that are not suitable to participate in this study, as judged by the investigator;
- •According to the judgment of the investigator, the presence of uterus (such as submucosal uterine fibroids, intermural uterine fibroids larger than 3 cm or smaller than 3 cm but affecting uterine cavity morphology, untreated endometrial polyps, uterine adhesions, uterine malformations, and ASRM stage Ⅲ-Ⅳ endometriosis). Patients with clinically significant ovarian (e.g., polycystic ovaries, ovarian cysts > 4 cm, inability to retrieve eggs from both or one ovary) or adnexa (e.g., hydrosalpinx) abnormalities;
- •Patients with unexplained abnormal uterine bleeding;
- •Patients with a history of ovarian, breast, uterus, hypothalamus, pituitary and other malignant tumors;
- •Receive donor egg or embryo preimplantation genetic screening/embryo preimplantation genetic diagnosis (PGS/PGD);
- •Known past or current thromboembolic disease;
- •Have a known serious mental illness or fail to understand the purpose and methods of the clinical trial, or fail to comply with the study procedures;
- •Patients with contraindications or allergic history to the use of GnRH-a, r-hFSH, hCGα, progesterone;
- •Those who are addicted to alcohol, tobacco, drugs or drug abuse;
- •Being exposed to teratogenic amounts of radiation, poisons and drugs and in the action period;
- •Patients with liver function injury, that is, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 2.5 times higher than the upper limit of normal values;
- •Persons who are HIV or syphilis positive;
- •Those with positive serum pregnancy tests;
- •Other reasons why the researcher considers it inappropriate to participate in the study. Suffers from a disease that is not suitable for the present assisted reproductive technology or for the present pregnancy;
- •Participants who had participated in other clinical trials within 3 months prior to screening.
结局指标
主要结局
Number of Day 3 embryos
时间窗: Day 3 of Embryo Culture
Number of Day 3 embryos
Number of Day 3 top-quality embryos
时间窗: Day 3 of Embryo Culture
embryos cultured to the third day post-fertilization that meet specific morphological criteria for optimal quality
Number of transferable embryos
时间窗: Day 3 of Embryo Culture
total number of embryos that meet predefined laboratory criteria for potential implantation
Blastocyst Formation Rate
时间窗: Day 6 of Embryo Culture
Blastocyst Formation Rate (BFR) = (Number of embryos reaching blastocyst stage ÷ Total embryos cultured to Day 5-6) × 100%
Follicle Counting
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Transvaginal ultrasound was performed using the Voluson S8 color Doppler ultrasound system (GE, USA) to measure the diameter and number of follicles in both ovaries.
Serum AMH Levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for AMH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
Serum FSH Levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for FSH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
ART outcomes assessed by the number of clinically viable embryos and clinical pregnancy rates
时间窗: From embryo transfer to the 14-day post-transfer clinical observation period
number of top-quality day 3 embryos and transferable embryos ；the blastocyst formation rate；the number of clinically usable embryos；clinical pregnancy rates
Serum LH Levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for LH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
Serum P Levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for P were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
Serum E2 Levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for E2 were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
Serum Testosterone levels
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Blood samples for testosterone were collected on days 2-3 of the menstrual cycle before ovarian stimulation.
Antral Follicle Count Retrived
时间窗: Immedietly after oocyte retrived
Transvaginal ultrasound was performed using the Voluson S8 color Doppler ultrasound system (GE, USA) to measure the diameter and number of follicles in both ovaries.
Oocytes Retrived
时间窗: Immedietly after oocyte retrived
Number of oocytes retrieved in Antagonist Protocol
NAD+ Levels in PBMCs
时间窗: At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
NAD+ levels and NAD+/NADH in PBMCs before and after medication
NAD+ Levels in GCs
时间窗: Immedietly after oocyte retrived
NAD+ levels and NAD+/NADH in GCs
次要结局
未报告次要终点
研究者
Qingling Yang
Associate Research Fellow
The First Affiliated Hospital of Zhengzhou University