Infertility Female
Conditions
Brief summary
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.
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.
Interventions
Sponsors
The First Affiliated Hospital of Zhengzhou University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 42 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NAD+ Levels in GCs | Immedietly after oocyte retrived | NAD+ levels and NAD+/NADH in GCs |
| Number of Day 3 embryos | Day 3 of Embryo Culture | Number of Day 3 embryos |
| Follicle Counting | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Immedietly after oocyte retrived | Number of oocytes retrieved in Antagonist Protocol |
| NAD+ Levels in PBMCs | 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 |
| Number of Day 3 top-quality embryos | 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 | Day 3 of Embryo Culture | total number of embryos that meet predefined laboratory criteria for potential implantation |
| Blastocyst Formation Rate | Day 6 of Embryo Culture | Blastocyst Formation Rate (BFR) = (Number of embryos reaching blastocyst stage ÷ Total embryos cultured to Day 5-6) × 100% |
Contacts
Primary ContactQingling Yang, Ph.D.
Backup ContactMengchen Wang, Master
Outcome results
None listed