NR vs. Vitamin E in Enhancing Fertility (NRVEERSAAM)

Nicotinamide Riboside vs. Vitamin E for Enhancing Fertility in Advanced Maternal Age: A Randomized Parallel Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility Female
• Intervention / Treatment: Dietary supplement: NR; Dietary supplement: Vit E

Detailed Description

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

Baseline measurements: Blood samples were obtained on day 2-3 of the menstrual cycle prior to medication initiation to assess basal endocrine profiles (FSH, LH, E2, P, T, PRL) and anti-Müllerian hormone (AMH) levels.

Post-intervention measurements: Repeat hormonal evaluations and transvaginal ultrasound assessments (antral follicle count [AFC]) were performed on day 2-3 of the third menstrual cycle after two months of supplementation.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qingling Yang, Ph.D.; Phone Number: +8666271879; Email: qingling531@163.com
• Study Contact Backup: Name: Mengchen Wang, Master; Phone Number: +86 66271879; Email: wmc13949362871@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Infertile women aged between 35 and 42 years;
2. 0.1 ng/mL <= AMH <= 1.1 ng/ml;
3. Pregnancy aids who plan to perform in vitro fertilization and embryo transfer (antagonist program);
4. Bilateral ovaries are present;
5. Patients who voluntarily signed the informed consent and agreed to be followed up according to the requirements of the study protocol.

Exclusion Criteria:

1. Adenomyosis and uterine fibroids compression of uterine uterine line;
2. Untreated bilateral hydrosalpinx;
3. Uncured endometrial disease;
4. Any pregnancy occurred within 3 months before screening;
5. Patients with clinically significant abnormal cervical examination results within 3 months before screening;
6. Use of fertility regulators (such as clomiphene citrate, GnRH, metformin or oral contraceptives) within 1 month before randomization;
7. Use hormone drugs within 1 month before randomization;
8. Patients with acute infection of urinary and reproductive system;
9. Patients with major systemic diseases, endocrine or metabolic abnormalities that are not suitable to participate in this study, as judged by the investigator;
10. 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;
11. Patients with unexplained abnormal uterine bleeding;
12. Patients with a history of ovarian, breast, uterus, hypothalamus, pituitary and other malignant tumors;
13. Receive donor egg or embryo preimplantation genetic screening/embryo preimplantation genetic diagnosis (PGS/PGD);
14. Known past or current thromboembolic disease;
15. 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;
16. Patients with contraindications or allergic history to the use of GnRH-a, r-hFSH, hCGα, progesterone;
17. Those who are addicted to alcohol, tobacco, drugs or drug abuse;
18. Being exposed to teratogenic amounts of radiation, poisons and drugs and in the action period;
19. 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;
20. Persons who are HIV or syphilis positive;
21. Those with positive serum pregnancy tests;
22. 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;
23. Participants who had participated in other clinical trials within 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NR; experimental group: 600 mg/d of oral NR, NIAGEN for two months	Dietary supplement: NR; 600 mg/d of oral NR for two months
Experimental: Vit E; control group: 200 mg/d of oral Vitamin E for two months	Dietary supplement: Vit E; 200 mg/d of oral Vitamin E for two months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follicle Counting	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.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Serum AMH Levels	Blood samples for AMH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Serum FSH Levels	Blood samples for FSH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
ART outcomes assessed by the number of clinically viable embryos and clinical pregnancy rates	number of top-quality day 3 embryos and transferable embryos ；the blastocyst formation rate；the number of clinically usable embryos；clinical pregnancy rates	From embryo transfer to the 14-day post-transfer clinical observation period
Serum LH Levels	Blood samples for LH were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Serum P Levels	Blood samples for P were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Serum E2 Levels	Blood samples for E2 were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Serum Testosterone levels	Blood samples for testosterone were collected on days 2-3 of the menstrual cycle before ovarian stimulation.	At the time of the first medication administration and on days 2-3 of the menstrual cycle during the second month of medication
Antral Follicle Count 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.	Immedietly after oocyte retrived
Oocytes Retrived	Number of oocytes retrieved in Antagonist Protocol	Immedietly after oocyte retrived
NAD+ Levels in PBMCs	NAD+ levels and NAD+/NADH in PBMCs before and after medication	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 in GCs	NAD+ levels and NAD+/NADH in GCs	Immedietly after oocyte retrived
Number of Day 3 embryos	Number of Day 3 embryos	Day 3 of Embryo Culture
Number of Day 3 top-quality embryos	embryos cultured to the third day post-fertilization that meet specific morphological criteria for optimal quality	Day 3 of Embryo Culture
Number of transferable embryos	total number of embryos that meet predefined laboratory criteria for potential implantation	Day 3 of Embryo Culture
Blastocyst Formation Rate	Blastocyst Formation Rate (BFR) = (Number of embryos reaching blastocyst stage ÷ Total embryos cultured to Day 5-6) × 100%	Day 6 of Embryo Culture

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): May 5, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 27, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 27, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: QNCXTD2023017 (Other Grant/Funding Number: The First Affiliated Hospital of Zhengzhou University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No