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.
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
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
60
Total of 900mg/day for 8 weeks
NMN-free placebo capsules for 8 weeks
IVF Namba Clinic, Sankaky Medical Corporation
Osaka, Osaka, Japan
RECRUITINGEmbryo development rate
Analyze and compare the transferable embryo rate per zygote on day 3 in between NMN and placebo intervention groups.
Time frame: 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
Time frame: Up to 8 weeks post-intervention
Clinical pregnancy rate
Compare ongoing clinical pregnancy rates between NMN and placebo groups
Time frame: Up to 12months post-intervention
Embryo development rate
Analyze and compare the quality of embryos on day 3, 5 or 6 between two groups
Time frame: 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
Time frame: Up to 8 weeks post-intervention
Live Birth rates
Compare live Birth rate following the intervention in both groups
Time frame: Up to 24 months post-intervention
Endocrine hormones including AMH
Changes in endocrine hormones including AMH levels in serum after the interventions.
Time frame: 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.
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Time frame: Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators
Number of average recruited MII oocytes in both groups
Time frame: Up to 8 weeks post-intervention
Chemical pregnancy rate
Compare the chemical pregnancy rates between the two groups.
Time frame: Up to 12months post-intervention
Pregnancy complication
Rate of pregnancy complication in both groups
Time frame: Up to 24 months post-intervention
Abortion rate
Compare the abortion rates in both groups
Time frame: Up to 24 months post-intervention
Additional in vitro fertilization - outcome indicators
Compare the rate of fertilization in between two groups
Time frame: Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators
Rate of abnormal fertilization in both groups
Time frame: Up to 8 weeks post-intervention
Additional in vitro fertilization - outcome indicators
The rate of non-transferable embryos in both groups
Time frame: Up to 8 weeks post-intervention