Is Nicotinamide mononucleotide (NMN) effective for improving fertility?

Nicotinamide Mononucleotide (NMN) for Fertility

NMN is not recommended for fertility preservation or enhancement based on current clinical practice guidelines, despite promising preclinical research showing potential benefits in animal models and limited human studies.

Guideline-Based Recommendations

Established Fertility Preservation Methods Take Priority

Major fertility organizations do not include NMN in their recommended interventions for fertility preservation. 1, 2

For females, evidence-based options include:

• Embryo or oocyte cryopreservation (most established method requiring ovarian stimulation) 1
• Ovarian tissue cryopreservation (experimental but with successful pregnancies reported) 1
• Oophoropexy for patients receiving pelvic radiation 1

For males, the gold standard remains:

• Semen cryopreservation before cancer treatment (most reliable and well-established method) 1
• Testicular sperm extraction (TESE) when ejaculated sperm is unavailable 1

Why NMN Is Not Guideline-Recommended

No major fertility guidelines from NCCN, ASCO, or other reproductive health societies mention NMN as a recommended intervention. 2 The absence from guidelines reflects:

• Lack of randomized controlled trials in humans 2
• Small sample sizes in existing studies 2
• No long-term follow-up data on pregnancy outcomes or offspring health 2
• No established optimal dosages for fertility enhancement 2

Research Evidence on NMN

Preclinical Findings (Animal Models)

The most recent and highest quality preclinical study shows promising results:

In chemotherapy-induced ovarian damage models, NMN supplementation (2 g/L in drinking water for 4 weeks) improved oocyte quality by:

• Recovering NAD+ levels (P=0.006) 3
• Improving fertilization rates (P=0.003) in diminished ovarian reserve mice 3
• Reducing reactive oxygen species (P=0.039) 3
• Enhancing mitochondrial function and DNA repair gene expression 3

Additional animal studies support these findings:

• NMN treatment restored fertility in aged mice by rejuvenating oocyte quality 4
• Supplementation increased ovulation rates and enhanced meiotic competency in naturally aged mice 5
• Benefits extended to early embryo development under toxic exposures 6

Limited Human Data

The only human evidence comes from in vitro studies using immature oocytes from women with advanced maternal age (>38 years):

• 100 µM NMN improved nuclear competence (P=0.039) and parthenogenetic activation of immature oocytes 3
• This represents laboratory findings only, not clinical pregnancy outcomes 3

Mechanism of Action

NMN works by:

• Restoring NAD+ levels, which decline with age and chemotherapy exposure 3, 4, 5
• Reducing oxidative stress and reactive oxygen species accumulation 3, 5, 7
• Improving mitochondrial function and energy metabolism 3, 5
• Enhancing DNA repair mechanisms 3
• Maintaining proper spindle assembly and chromosome alignment during meiosis 3, 5

Clinical Approach

For Patients Seeking Fertility Preservation

Prioritize established evidence-based interventions over experimental supplements like NMN. 1

1. Immediate referral to fertility specialist (within 24 hours for cancer patients) 1
2. Discuss proven options first:
   • Embryo/oocyte cryopreservation for females (can use random-start protocols if time-sensitive) 1
   • Sperm banking for males 1
3. Risk stratification based on planned treatment:
   • High-risk: alkylating agents, pelvic radiation ≥2 Gy, total body irradiation 1
   • Moderate-risk: platinum agents, procarbazine-based regimens 1

If Patients Inquire About NMN

Counsel that NMN is not part of standard fertility preservation protocols and lacks human clinical trial data. 2

Key counseling points:

• Animal studies show promise but do not translate directly to human clinical outcomes 3, 4, 5
• No established dosing, safety profile, or efficacy data in humans seeking fertility 2
• Generally well-tolerated at recommended dosages, but potential gastrointestinal side effects may occur 2
• Should not replace or delay proven fertility preservation methods 2

Common Pitfalls to Avoid

1. Do not recommend NMN as a fertility preservation strategy in place of established methods 1, 2
2. Do not delay proven interventions while patients pursue experimental supplements 1
3. Avoid conflating animal research with human clinical efficacy when counseling patients 2, 3
4. Do not assume supplements are risk-free without proper medical oversight 2

Special Populations

Cancer Patients

Fertility preservation discussions must occur before starting gonadotoxic therapy. 1

• Document infertility risk based on planned treatment regimen 1
• Alkylating agents and pelvic radiation pose highest risk for permanent infertility 1
• GnRH agonists are NOT effective for fertility preservation despite some data on menstrual protection 1, 8

Advanced Maternal Age

For women >38 years seeking pregnancy, focus on optimizing ovarian reserve assessment and assisted reproductive technology rather than unproven supplements. 3

• Anti-Müllerian hormone (AMH) and antral follicle count (AFC) guide treatment planning 1
• In vitro fertilization with preimplantation genetic testing may be more beneficial than experimental interventions 1