Can NMN Improve Oocyte Quality? Current Evidence in Fertility Care

“We retrieved oocytes, but none were of good quality.” “My AMH level is low.” These concerns point to a problem encountered repeatedly in fertility care: the age-related decline in oocyte quality.

AMH

A blood marker of ovarian reserve—the number of oocytes remaining in the ovaries.

According to the Assisted Reproductive Technology data book published by the Japan Society of Obstetrics and Gynecology, approximately 543,000 in vitro fertilization (IVF) procedures were performed in Japan in 2022. About one in every 11 children born that year was reportedly conceived through IVF. At the same time, the live birth rate per oocyte retrieval declines rapidly after age 35 and may fall to around 10% by age 40¹.

ART

Assisted reproductive technology.

Despite major advances in IVF and intracytoplasmic sperm injection (ICSI), oocyte quality remains one of the central factors influencing treatment success². Oocyte quality declines irreversibly with age, and no established treatment currently improves the intrinsic quality of oocytes. This remains a major challenge in fertility care.

Against this background, reproductive medicine researchers have begun to investigate NMN. Previous articles on this site have discussed how NMN increases NAD+ and how NAD+ is related to physical performance. In 2025, a leading obstetrics and gynecology journal published a study testing NMN in human oocytes, which the authors described as the first report of its kind³. A field previously dominated by animal studies is now beginning to include human-derived data.

This article reviews the latest evidence on NMN and oocyte quality, from basic research to early clinical findings.

What You Will Learn

• What “oocyte aging” involves and why declining NAD+ may be important
• The proposed mechanisms through which NMN may affect oocytes
• Findings from a 2025 study using human oocytes
• Other notable evidence, including animal studies, a pilot AMH study, and ESHRE 2025 data

Why Do Oocytes Age? The Roles of Mitochondria and NAD+

Oocytes are known to contain an exceptionally large number of mitochondria compared with many other human cell types. Oocyte-derived mitochondria provide most of the energy needed for fertilization, implantation, and early embryonic development. NAD+ is an essential coenzyme that mitochondria require to produce this energy.

Mitochondria

Small structures within cells that generate energy.

NAD+ levels decline with aging, and the same decline occurs in oocytes. Research suggests that NAD+ depletion may initiate the following sequence of changes within oocytes:

1. Energy deficiency: Impaired mitochondrial function reduces the ATP available for fertilization and embryonic development.
2. Chromosome segregation errors: The machinery that distributes chromosomes evenly becomes disrupted, increasing the likelihood of oocytes with an abnormal chromosome number.
3. Oxidative damage: Reactive oxygen species accumulate and damage structures within the oocyte.
4. Impaired DNA repair: Damage to genetic material is not repaired efficiently and may accumulate.

ATP

The energy currency used by cells. It is produced in mitochondria and fuels a wide range of biological processes.

Chromosomes

Bundles of genetic information within cells. Humans normally have 46 chromosomes.

Reactive oxygen species

Highly reactive oxygen-containing molecules generated during processes such as respiration. At low levels, they contribute to functions such as biological defense. In excess, however, they can damage cells and DNA and contribute to aging and functional decline.

Clinical significance

Low oocyte maturation rates, failure to reach the blastocyst stage, and recurrent miscarriage after implantation may involve mitochondrial dysfunction associated with declining NAD+ levels.

How, then, might the deterioration of oocyte function associated with NAD+ depletion be addressed? Recent research has focused on NMN, a precursor of NAD+.

Proposed Mechanisms Through Which NMN May Affect Oocytes

Animal studies have repeatedly indicated that NMN may act on oocytes through three main pathways:

• Mitochondrial support: Replenishing NAD+ may restore energy production.
• Antioxidant effects: NMN may reduce damage to oocytes caused by reactive oxygen species.
• Support for DNA repair: NMN may help sustain the repair of damaged genetic material.

In other words, NMN is being studied as a candidate that may intervene upstream in the sequence from NAD+ depletion to impaired oocyte function. The remaining question is straightforward: Do the same processes occur in human oocytes? Research published since 2025 has begun to address this question.

What Human Oocytes Have Revealed, Part 1: Integrated Analysis (Hum Reprod Update, 2025)

In 2025, Ramírez-Martín and colleagues integrated findings from seven preclinical studies and performed comprehensive, single-oocyte gene-expression analyses of 46 human oocytes⁴.

The analysis indicated that the genes active as oocytes progressed from immature to mature stages overlapped with NMN-related NAD+ pathways in three areas:

• Energy production: Genes that regulate mitochondrial energy generation
• Control of oxidative stress: Genes that remove reactive oxygen species and protect oocytes
• Mitochondrial maintenance: Genes that regulate mitochondrial division and turnover

The pathways implicated in animal studies therefore overlapped with pathways active in human oocytes. This early report provided gene-expression evidence supporting the hypothesis that NMN could also act through relevant pathways in humans. It did not, however, establish a clinical benefit from NMN supplementation.

What Human Oocytes Have Revealed, Part 2: Improved Maturation During IVM (AJOG, 2025)

The same research group subsequently published an in vitro maturation study using human immature oocytes in the American Journal of Obstetrics and Gynecology (AJOG), a leading journal in obstetrics and gynecology³.

Study Design

• Design: In vitro maturation (IVM) study using human immature oocytes
• Participants: Immature oocytes collected from women with infertility aged 38 or older; oocytes from women aged 35 or younger were used as the younger control group
• Intervention: In vitro maturation in culture medium containing NMN
• Primary outcomes: Nuclear maturation rate—the proportion of oocytes reaching a stage compatible with fertilization—and parthenogenetic activation rate, an indicator of the oocyte’s ability to begin development without sperm
• Institution: IVI Foundation, Spain

IVM (in vitro maturation)

A technique in which immature oocytes collected during retrieval are cultured and matured outside the body. Unlike conventional IVF, which generally retrieves mature oocytes, IVM involves maturing immature oocytes after retrieval.

Results

• In oocytes from women aged 38 or older, adding NMN produced a statistically significant improvement in the nuclear maturation rate.
• The parthenogenetic activation rate also improved.
• No comparable difference was observed in the group aged 35 or younger, suggesting an age-specific effect in the oocytes studied.

Interpretation

This study provides proof of concept. It does not mean that NMN can immediately be introduced as an IVM treatment. A more detailed interpretation of this individual study appears in the Discussion section below.

Other Notable Evidence

Evidence concerning NMN and oocyte quality is also accumulating from several other directions.

Animal Studies: Recovery in Aging and Obesity Models

Multiple independent studies in aged mice have reported that oral NMN administration increased the number of ovulated oocytes, restored mitochondrial function, reduced reactive oxygen species, improved fertilization and blastocyst formation rates, and produced a significant increase in offspring number⁵, ⁶. In obese mice, studies have also reported improvements in ovarian inflammation, structural abnormalities in oocytes, and DNA damage⁷. Repeated findings across models with different underlying conditions support the biological plausibility of NMN’s effects, but they do not demonstrate the same outcomes in humans.

Japanese Pilot Study: An Approximately 40% Increase in AMH

In 2024, a joint research team from Medical Park Shonan and Santé Research Institute announced results from a pilot study in which healthy women in their 30s and 40s took NMN orally for two months. The team reported an average increase of approximately 40% in AMH⁸. However, the detailed study design was not sufficiently disclosed in the press release, and publication in a peer-reviewed journal has not been confirmed. Reproducibility must be tested in a larger, placebo-controlled randomized controlled trial.

ESHRE 2025: Possible Benefits of NMN in Patients With Diminished Ovarian Reserve

In June 2025, Dr. Sen Sharma presented a retrospective study at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE). The study included 50 women under age 35 with diminished ovarian reserve (DOR)⁹. Compared with the control group, the group that received oral NMN alongside ovarian stimulation (25 participants per group) had a twofold pregnancy rate (48% vs 24%) and required approximately half the gonadotropin dose (267 IU vs 471 IU), with statistically significant between-group differences. The miscarriage rate was also numerically lower (8.3% vs 16.7%), and several measures favored the NMN group. Although this was a small retrospective study, reported only at a conference and conducted at a single center, it represents early clinical data on the possibility that oral NMN could influence outcomes in fertility treatment.

Gonadotropins

Hormones that stimulate the gonads and are used to induce ovulation in fertility treatment and to treat hypogonadism.

Ongoing Clinical Trials

Trials of NMN in reproductive medicine, including NCT06629636 and NCT06426355, are registered on ClinicalTrials.gov. Medical Park Shonan is also conducting a clinical trial involving a larger number of women with infertility in Japan. When these results become available, they may provide a clearer scientific answer to whether NMN could serve as an adjunct to fertility treatment.

Comparison of Three Human or Clinical Studies

• AJOG 2025 (³)
• Population: Immature oocytes from women with infertility aged 38 or older
• Intervention: NMN added to IVM culture medium (in vitro)
• Main findings: Significant improvements in nuclear maturation and parthenogenetic activation rates
• Evidence level: In vitro study using human oocytes
• Main limitation: Effects of oral supplementation were not tested
• Japanese pilot study, 2024 (⁸)
• Population: Healthy women in their 30s and 40s
• Intervention: Oral NMN for two months
• Main finding: An average increase of approximately 40% in AMH was reported
• Evidence level: Press release; no peer-reviewed publication identified
• Main limitations: No placebo control and insufficient disclosure of the study design
• ESHRE 2025 (⁹)
• Population: Women under age 35 with DOR; n=50, with 25 participants per group
• Intervention: Oral NMN alongside an ovarian stimulation cycle
• Main findings: A twofold pregnancy rate (48% vs 24%) and approximately half the gonadotropin requirement
• Evidence level: Retrospective study presented at a conference
• Main limitations: Small, single-center study reported only as a conference presentation

Discussion: What the Current Evidence Suggests

The question of whether NMN could become an adjunct to fertility treatment is being examined through several types of evidence: in vitro experiments using human oocytes, in vivo studies involving oral administration in animals, and small studies of oral supplementation in humans.

The approximately 50% reduction in gonadotropin use (267 IU vs 471 IU) reported at ESHRE 2025 could have practical implications if replicated in a large randomized controlled trial. Fertility treatment can involve frequent injections, substantial costs, and a considerable physical burden. A reproducible reduction of this magnitude could therefore be clinically meaningful.

However, there are still very few data directly measuring the extent to which orally consumed NMN increases NAD+ within human oocytes. Further research is needed to determine whether the effects observed in vitro also occur after oral supplementation.

Current State of the Evidence

• Positive findings have been reported in human oocytes: Adding NMN significantly improved the nuclear maturation rate in oocytes from women aged 38 or older in an in vitro study (AJOG, 2025).
• Animal studies have reported consistent effects: Oocyte quality and fertility-related outcomes improved in aging and obesity models.
• Early clinical data are accumulating: A Japanese pilot study reported an approximately 40% increase in AMH, and ESHRE 2025 data suggested possible benefits of NMN in patients with DOR.
• Definitive evidence from large randomized controlled trials is not yet available: Multiple clinical trials are currently underway.

Remaining Questions

• Lack of large randomized controlled trials: The ESHRE 2025 report was a retrospective study of 50 participants, while the Japanese pilot study was a single-arm study without a placebo control. Multicenter, double-blind, placebo-controlled randomized controlled trials are essential for definitive evidence.
• Optimization of dose and duration: The optimal treatment phase—before oocyte retrieval, during ovarian stimulation, or alongside IVM—as well as the appropriate duration and dose remain undetermined.
• Long-term safety: Short-term tolerability data are accumulating, but long-term follow-up concerning pregnancy and embryonic development remains limited.

Several prospective clinical trials are in progress. Their results should advance the field beyond its current state, in which the findings are suggestive but not definitive.

Important Considerations

NMN has generally shown favorable tolerability in several human clinical studies. However, anyone undergoing fertility treatment or planning a pregnancy should consult their treating physician before considering NMN supplementation. Potential interactions with ovulation-inducing medications and the appropriateness of NMN use during an embryo-transfer cycle require individualized clinical judgment. In addition, the optimal dose for people trying to conceive or receiving fertility treatment has not been established.

This article does not recommend the use of any particular supplement or claim that a specific product is effective. Its purpose is to explain current research.

References

1. 日本産科婦人科学会「ARTデータブック 2022年」. ↩
2. 日本生殖医学会「生殖医療Q&A Q24．加齢に伴う卵子の質の低下について」. http://www.jsrm.or.jp/public/funinsho_qa24.html ↩
3. Ramírez-Martín N et al., Nicotinamide mononucleotide supplementation improves oocyte developmental competence in different ovarian damage conditions. Am J Obstet Gynecol. 2025; 233: 112.e1–20. ↩
4. Ramírez-Martín N et al., NMN supplementation as a strategy to improve oocyte quality: a systematic review and transcriptomic analysis. Hum Reprod Update. 2025. ↩
5. Miao Y et al., Nicotinamide mononucleotide supplementation reverses the declining quality of maternally aged oocytes. Cell Rep. 2020 Sep 22; 32(12): 108209. ↩
6. Bertoldo MJ et al., NAD+ repletion rescues female fertility during reproductive aging. Cell Rep. 2020 Feb 11; 30(6): 1670–1681. ↩
7. Luo C et al., Administration of nicotinamide mononucleotide improves oocyte quality of obese mice. Cell Prolif. 2022; 55(11): e13303. ↩
8. メディカルパーク湘南・株式会社サンテ研究所「NMNサプリメントによる卵巣予備能の改善効果」共同通信PRワイヤー. 2024年10月9日（プレスリリース・未査読）. ↩
9. Sen Sharma D, Nicotinamide mononucleotide—a NAD+ precursor—a new hope for rejuvinating fertility outcome in young infertile women with diminished ovarian reserve: a retrospective analysis. Hum Reprod. 2025; 40(Supplement_1): deaf097.217. ↩