Clinical trial NCT06629636: Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity.
Official title: Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity and IVF Success Rate in Patients Who Have Experienced IVF Failures.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Repeated IVF Failure
Female Infertility
Keywords: IVF failure
NMN
Female Infertility
Japan
Oocyte Mitochondria
Anti aging
Lead sponsor: Sunkaky Medical Cooperation
Sponsor class: INDUSTRY
Collaborators: name: Abinopharm, Inc
name: Aba Chemicals Co Ltd
First posted: 2024-10-08
Enrollment: 60
Sex: FEMALE
Minimum age (years): 32
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dietary Supplement: NMN intervention NMN capsules (total of 900mg/day) for 8 weeks, NMN capsules (total of 900mg/day) for 8 weeks Placebo Comparator: Placebo intervention

Placebo NMN-free placebo capsules for 8 weeks Other:

Placebo, for 8 weeks
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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 \&lt;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.

Primary outcomes:
measure: Embryo development rate
timeFrame: Up to 8 weeks post-intervention
measure: Changes in metabolic status
timeFrame: Up to 8 weeks post-intervention
measure: Clinical pregnancy rate
timeFrame: Up to 12months post-intervention
measure: Embryo development rate
timeFrame: Up to 8 weeks post-intervention
measure: Embryo development rate
timeFrame: Up to 8 weeks post-intervention
Secondary outcomes:
measure: Live Birth rates
timeFrame: Up to 24 months post-intervention
measure: Endocrine hormones including AMH
timeFrame: Up to 8 weeks post-intervention
measure: Average egg retrieval capacity per person
timeFrame: Up to 8 weeks post-intervention
measure: Additional in vitro fertilization - outcome indicators
timeFrame: Up to 8 weeks post-intervention
measure: Chemical pregnancy rate
timeFrame: Up to 12months post-intervention
measure: Pregnancy complication
timeFrame: Up to 24 months post-intervention
measure: Abortion rate
timeFrame: Up to 24 months post-intervention
measure: Additional in vitro fertilization - outcome indicators
timeFrame: Up to 8 weeks post-intervention
measure: Additional in vitro fertilization - outcome indicators
timeFrame: Up to 8 weeks post-intervention
measure: Additional in vitro fertilization - outcome indicators
timeFrame: Up to 8 weeks post-intervention
Other outcomes:
Locations:
city: Osaka
country: Japan
facility: IVF Namba Clinic, Sankaky Medical Corporation
Study officials:
affiliation: Sankaky Medical Corporation
name: Yoshiharu M., Yoshiharu Morimoto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sankaky Medical Corporation
name: Naoharu M., Naoharu Yoshiharu, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.