Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity.

Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity and IVF Success Rate in Patients Who Have Experienced IVF Failures.

The objective of this study is to investigate the efficacy of NMN supplementation in enhancing embryo developmental capacity and improving IVF success rates in patients experiencing IVF failures.

Study Overview

• Status: Recruiting
• Conditions: Female Infertility; Repeated IVF Failure
• Intervention / Treatment: Other: Placebo; Dietary supplement: NMN capsule

Detailed Description

Reproductive aging is an irreversible process characterized by a decline in oocyte quality, posing a significant challenge to fertility and often leading to unsuccessful outcomes in assisted reproductive technologies. Repeated ART failures can result in substantial burdens for patients, both financially and emotionally. Extensive clinical and preclinical data have established a strong correlation between age-related decline in egg quality and mitochondrial deterioration, resulting in decreased energy production within oocytes. Notably, a reduction in nicotinamide adenine dinucleotide (NAD+ / NADH) concentrations, a crucial redox cofactor and enzyme-substrate essential for energy metabolism, DNA repair, and epigenetic homeostasis, has been observed in various tissues with age.

Recent studies on mice have indicated that Nicotinamide mononucleotide supplementation may mitigate the age-related decline in NAD(P)H levels, enhancing the quality of aged oocytes. This improvement is achieved by promoting both nuclear and cytoplasmic maturation, ensuring euploidy and fertilization competence, ultimately leading to an increased ovulation rate and improved fertility. Moreover, NMN has been shown to restore mitochondrial function in aged oocytes, effectively suppressing the accumulation of reactive oxygen species and DNA damage, and subsequently reducing apoptosis.

Clinical studies have further corroborated the safety and tolerability of NMN supplementation, with daily oral doses of up to 900 mg demonstrating an increase in blood NAD concentrations. Furthermore, research suggests that a daily oral dose of 900 mg maximizes clinical efficacy, as evidenced by blood NAD concentration and physical performance.

This study adopts a triple-blind, randomized, placebo-controlled, prospective pilot study design. This prospective study aims to evaluate the effects of dietary supplementation with 900mg of NMN on ART outcomes in individuals experiencing in vitro fertilization failures attributed to compromised oocyte and embryo quality.

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

Contacts and Locations

• Study Contact: Name: Udayanga KGS., Udayanga Gamage, BVSc, PhD; Phone Number: +81 90 9823 8477; Email: udayanga646@ivfjapan.com
• Study Contact Backup: Name: Masaya Y., Masaya Yamanaka, BSc; Phone Number: +81 80 4344 2654; Email: yamanaka086@ivfjapan.com

Study Locations

• Japan
  • Osaka, Japan, 5500015
    • Recruiting
    • IVF Namba Clinic, Sankaky Medical Corporation
    • Contact: Naoharu M., Naoharu Morimoto, MD; Phone Number: +81 6 6534 8824; Email: morimoto003@ivfjapan.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Agree to participate in the study
• 32-42 years old
• Having at least one previous embryo implantation failure
• History of low Embryo quality at day3 or day5 (according to Veeck's and Gardner's Criteria)
• No major uterine or ovarian abnormalities
• BMI level 18-25kg/m2

Exclusion Criteria:

• Ovarian endometriosis with Chocolate cysts (AFS type 3 and 4)
• Patients who have taken different supplements such as coenzyme Q10, vitamin E, carnitine,niacin, nicotinamide, or other vitamin B3-related etc. within the previous month
• Any medical contraindication of oocyte retrieval or subsequent procedures
• Couples where the husband presents with severe sperm abnormalities
• Couples where the husband presents <5 million/mL motile sperm
• Uterine structural anomalies
• Polycystic ovaries
• Premature ovarian failure
• Individuals who need regular medication to treat chronic diseases such as diabetes, hypertension, gout, hyperuricemia, etc.
• Individuals who need drug treatment for any mental illness such as epilepsy and depression.
• Individuals who suffer from infectious diseases such as hepatitis B, active tuberculosis, AIDS, etc.
• Cancer patients or receiving chemo/radiotherapy treatment within the past 3 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NMN intervention; NMN capsules (total of 900mg/day) for 8 weeks	Dietary supplement: NMN capsule; Total of 900mg/day for 8 weeks
Placebo Comparator: Placebo intervention; NMN-free placebo capsules for 8 weeks	Other: Placebo; NMN-free placebo capsules for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Embryo development rate	Analyze and compare the transferable embryo rate per zygote on day 3 in between NMN and placebo intervention groups.	Up to 8 weeks post-intervention
Changes in metabolic status	Analyze and compare the NAD+/NADH level in serum and follicular fluid in both NMN and placebo groups	Up to 8 weeks post-intervention
Clinical pregnancy rate	Compare ongoing clinical pregnancy rates between NMN and placebo groups	Up to 12months post-intervention
Embryo development rate	Analyze and compare the quality of embryos on day 3, 5 or 6 between two groups	Up to 8 weeks post-intervention
Embryo development rate	Analyze and compare the rate of blastocyst development on day 5 and 6 in between two groups	Up to 8 weeks post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live Birth rates	Compare live Birth rate following the intervention in both groups	Up to 24 months post-intervention
Endocrine hormones including AMH	Changes in endocrine hormones including AMH levels in serum after the interventions.	Up to 8 weeks post-intervention
Average egg retrieval capacity per person	Compare the number of antral follicles in each ovary will be determined using transvaginal ultrasonography in both groups.	Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators	Number of average recruited MII oocytes in both groups	Up to 8 weeks post-intervention
Chemical pregnancy rate	Compare the chemical pregnancy rates between the two groups.	Up to 12months post-intervention
Pregnancy complication	Rate of pregnancy complication in both groups	Up to 24 months post-intervention
Abortion rate	Compare the abortion rates in both groups	Up to 24 months post-intervention
Additional in vitro fertilization - outcome indicators	Compare the rate of fertilization in between two groups	Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators	Rate of abnormal fertilization in both groups	Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators	The rate of non-transferable embryos in both groups	Up to 8 weeks post-intervention

Collaborators and Investigators

• Sponsor: Sunkaky Medical Cooperation
• Collaborators: Abinopharm, Inc; Aba Chemicals Co Ltd
• Investigators: Principal Investigator: Yoshiharu M., Yoshiharu Morimoto, MD, PhD, Sankaky Medical Corporation; Study Director: Naoharu M., Naoharu Yoshiharu, MD, Sankaky Medical Corporation

Publications and helpful links

General Publications

• Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front Aging. 2022 May 5;3:851698. doi: 10.3389/fragi.2022.851698. eCollection 2022.
• Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023 Feb;45(1):29-43. doi: 10.1007/s11357-022-00705-1. Epub 2022 Dec 8.
• Miao Y, Cui Z, Gao Q, Rui R, Xiong B. Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes. Cell Rep. 2020 Aug 4;32(5):107987. doi: 10.1016/j.celrep.2020.107987.
• Bertoldo MJ, Listijono DR, Ho WJ, Riepsamen AH, Goss DM, Richani D, Jin XL, Mahbub S, Campbell JM, Habibalahi A, Loh WN, Youngson NA, Maniam J, Wong ASA, Selesniemi K, Bustamante S, Li C, Zhao Y, Marinova MB, Kim LJ, Lau L, Wu RM, Mikolaizak AS, Araki T, Le Couteur DG, Turner N, Morris MJ, Walters KA, Goldys E, O'Neill C, Gilchrist RB, Sinclair DA, Homer HA, Wu LE. NAD+ Repletion Rescues Female Fertility during Reproductive Aging. Cell Rep. 2020 Feb 11;30(6):1670-1681.e7. doi: 10.1016/j.celrep.2020.01.058.
• Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab. 2016 Jun 14;23(6):965-966. doi: 10.1016/j.cmet.2016.05.022.
• Bentov Y, Yavorska T, Esfandiari N, Jurisicova A, Casper RF. The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet. 2011 Sep;28(9):773-83. doi: 10.1007/s10815-011-9588-7. Epub 2011 May 27.
• Hashimoto S, Morimoto Y. Mitochondrial function of human embryo: Decline in their quality with maternal aging. Reprod Med Biol. 2022 Dec 21;21(1):e12491. doi: 10.1002/rmb2.12491. eCollection 2022 Jan-Dec.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 3, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Japan; Female Infertility; NMN; IVF failure; Anti aging; Oocyte Mitochondria
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: IVFJapan202402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The confidentiality of patients' information is strictly maintained.

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