- Daily 600 mg NMN Put to the Test in 200 Women with Diminished Ovarian Reserve: Randomized clinical trials registered to assess clinical pregnancy and live birth rates
- Maturation Rate of Immature Eggs in Poor-Prognosis Women Aged 37–45 Rose from 28.8% to 50.7%… But improvements in chromosomal normality (euploidy) remain unconfirmed
- Human Clinical Evidence Still in Its Infancy… Premature to label it an “egg rejuvenation supplement”
For women facing advanced maternal age and diminished ovarian reserve, the search for supportive therapies is ongoing. While supplements like Coenzyme Q10 (CoQ10) and DHEA have long been commonly used, NMN (Nicotinamide Mononucleotide) has recently gained attention as a prospective anti-aging adjuvant.
NMN is a direct precursor to NAD+ (Nicotinamide Adenine Dinucleotide), a critical coenzyme involved in cellular energy metabolism, mitochondrial function, and DNA repair. In short, NMN provides the cellular building blocks required for the body to synthesize NAD+.
The interest in NMN extends beyond popular wellness trends. Preliminary human clinical trials in women with diminished ovarian reserve (DOR) are beginning to appear, and a double-blind, randomized controlled trial (RCT) investigating IVF pregnancy and live birth outcomes in 200 patients is currently registered. However, scientific evidence demonstrating that NMN can definitively “reverse oocyte aging” in humans remains insufficient.
A clinical distinction must be maintained: diminished ovarian reserve is not synonymous with poor oocyte quality.
- Ovarian Reserve (AMH and Antral Follicle Count [AFC]): Reflects the quantitative pool of remaining oocytes. As noted by the American Society for Reproductive Medicine (ASRM), ovarian reserve metrics gauge egg quantity rather than intrinsic egg competence.
- Oocyte Quality: Heavily driven by maternal age, which dictates the rate of chromosomal errors (aneuploidy).
Consequently, young women with low reserve and older women facing age-related ovarian decline represent distinct clinical cohorts.
ESHRE 2025: 50-Patient Preliminary Cohort
A preliminary human study presented at the 2025 Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) evaluated 50 women under age 35 with DOR (AMH<1.0 ng/mL, AFC<5):
- Study Cohort: 25 patients received ovulation induction combined with oral NMN, while 25 received standard ovulation induction alone.
- Reported Outcome: 12 pregnancies (48%) were reported in the NMN arm versus 6 pregnancies (24%) in the control arm.
While these raw figures appear notable, the data cannot be interpreted as conclusive proof of efficacy:
- The data originates from a conference abstract rather than a peer-reviewed paper.
- The abstract described the design as a retrospective analysis while concurrently noting randomized allocation, presenting methodological inconsistencies.
- The sample size (n=50) is small, lacks a registered clinical trial identifier, and conflates intermediary fertility metrics. The authors noted that large-scale RCTs are necessary to confirm effects on pregnancy and live birth rates.
In Vitro Maturation (ESHRE 2026): Oocyte Maturation vs. Euploidy
A laboratory study presented at ESHRE 2026 examined the direct in vitro effects of NMN on 840 immature germinal vesicle (GV) oocytes retrieved during IVF cycles (582 oocytes from women aged 19–36; 258 from women aged 37–45):
- Maturation Rescue: Immature GV oocytes were matured in vitro with or without NMN supplementation. Overall maturation to the Metaphase II (MII) stage reached 53.1% with NMN vs. 44.5% in controls.
- Advanced Age Cohort (37–45 years): The maturation rate of poor-prognosis immature oocytes rose from 28.8% to 50.7% with NMN (P=0.007).
Despite the improved maturation rate, downstream chromosomal analysis showed important limitations:
- No Euploidy Improvement in Older Oocytes: NMN supplementation did not yield a statistically significant improvement in the euploidy rate of matured oocytes from women aged 37–45.
- Aneuploidy Signal in Young Cohort: In poor-prognosis oocytes from younger women, the euploidy rate was unexpectedly lower in the NMN-supplemented arm (25.0% vs. 83.3%, P=0.031). While small sample sizes preclude declaring this a definitive adverse effect, it highlights the need for caution.
Crucially, this study investigated in vitro exposure of retrieved oocytes in laboratory culture media—it did not evaluate oral NMN supplementation in patients. An increase in the raw number of mature oocytes does not automatically equate to an increase in chromosomally normal embryos.
Ongoing Large-Scale RCTs in Human IVF
To evaluate whether oral NMN supplementation impacts clinical IVF outcomes, a clinical trial was registered at Peking University Third Hospital:
- Target Population: 200 women aged 20–40 with diminished ovarian reserve (AMH<1.1 ng/mL, AFC<7, or Day-3 FSH 10–20 IU/L).
- Intervention: NMN 600 mg/day orally for 2 to 5 months versus placebo.
- Primary Endpoint: Clinical pregnancy rate, along with tracked secondary outcomes including embryo development, biochemical pregnancy, miscarriage rates, live birth rates, and neonatal health.
Peer-reviewed clinical results from this registered trial have not yet been published. ClinicalTrials.gov records indicate the study completion target was set for 2026–2027. Another trial evaluating 200 patients with DOR or premature ovarian insufficiency (POI) using 600 mg/day for 3 months currently lists its recruitment status as “Unknown” without published results.
Current Consensus from Systematic Reviews and Guidelines
A systematic review published in the Journal of Assisted Reproduction and Genetics (JARG) evaluated the literature on NMN and oocyte quality:
- Exclusively Preclinical: All 7 included interventional studies were conducted in animal models (primarily rodents).
- Human Data Scope: Analysis of 46 human oocytes was restricted to transcriptomic profiling of NAD+ and mitochondrial pathways during maturation, rather than interventional trials of oral supplementation.
- Review Finding: While NMN consistently improves mitochondrial function, reduces oxidative stress, and enhances oocyte parameters in aging animal models, standardized human clinical trials are required before translating findings into reproductive medicine.
A review published in Clinical and Experimental Reproductive Medicine (CERM) reached a similar conclusion: despite promising rodent data, robust clinical data establishing efficacy, optimal dosing, and long-term reproductive safety in humans remain lacking.
Furthermore, current clinical practice guidelines for ovarian stimulation from ESHRE do not recommend NMN for poor ovarian responders or DOR patients, as it has not attained standard evidence-based status.
Clinical Takeaways
The biological rationale behind NMN—replenishing age-depleted NAD+ pools to support mitochondrial bioenergetics and cellular repair—is biologically sound in animal models.
However, clinical translation requires clearing rigorous benchmarks:
- Demonstrating improvements not just in surrogate markers (e.g., AMH, retrieved oocyte numbers, or in vitro maturation rates), but in euploid blastocyst yields and cumulative live birth rates.
- Ensuring maternal, fetal, and neonatal safety through adequately powered, randomized, placebo-controlled human trials.
NMN currently represents an experimental investigational molecule under clinical study, rather than an established, evidence-based therapy for age-related reproductive decline.
※ This article was synthesized based on clinical trials registered on ClinicalTrials.gov, research presented at the 2025 and 2026 ESHRE Annual Meetings, systematic reviews from the Journal of Assisted Reproduction and Genetics (JARG) and Clinical and Experimental Reproductive Medicine (CERM), and guidelines from the American Society for Reproductive Medicine (ASRM) and ESHRE. It does not replace individualized medical advice, diagnosis, or clinical treatment.
※ The images associated with this article were generated using generative AI (ChatGPT, OpenAI) as illustrative references and do not depict real individuals.