Female Infertility, Repeated IVF Failure
Conditions
Keywords
IVF failure, NMN, Female Infertility, Japan, Oocyte Mitochondria, Anti aging
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.
Interventions
DIETARY_SUPPLEMENTNMN capsule
Total of 900mg/day for 8 weeks
OTHERPlacebo
NMN-free placebo capsules for 8 weeks
Sponsors
Abinopharm, Inc
Aba Chemicals Co Ltd
Sunkaky Medical Cooperation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
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
Eligibility
Sex/Gender
FEMALE
Age
32 Years to 42 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Embryo development rate | Up to 8 weeks post-intervention | Analyze and compare the transferable embryo rate per zygote on day 3 in between NMN and placebo intervention groups. |
| Changes in metabolic status | Up to 8 weeks post-intervention | Analyze and compare the NAD+/NADH level in serum and follicular fluid in both NMN and placebo groups |
| Clinical pregnancy rate | Up to 12months post-intervention | Compare ongoing clinical pregnancy rates between NMN and placebo groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional in vitro fertilization - outcome indicators | Up to 8 weeks post-intervention | Number of average recruited MII oocytes in both groups |
| Chemical pregnancy rate | Up to 12months post-intervention | Compare the chemical pregnancy rates between the two groups. |
| Live Birth rates | Up to 24 months post-intervention | Compare live Birth rate following the intervention in both groups |
| Abortion rate | Up to 24 months post-intervention | Compare the abortion rates in both groups |
| Pregnancy complication | Up to 24 months post-intervention | Rate of pregnancy complication in both groups |
| Endocrine hormones including AMH | Up to 8 weeks post-intervention | Changes in endocrine hormones including AMH levels in serum after the interventions. |
| Average egg retrieval capacity per person | Up to 8 weeks post-intervention | Compare the number of antral follicles in each ovary will be determined using transvaginal ultrasonography in both groups. |
Countries
Japan
Contacts
Primary ContactUdayanga KGS., Udayanga Gamage, BVSc, PhD
Backup ContactMasaya Y., Masaya Yamanaka, BSc
Outcome results
None listed