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.

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.

The confidentiality of patients' information is strictly maintained.