Is NMN (Nicotinamide Mononucleotide) supplementation effective for improving fertility outcomes in patients with Polycystic Ovary Syndrome (PCOS) and infertility?

NMN in Infertility and PCOS

Direct Answer

There is no evidence supporting the use of NMN (Nicotinamide Mononucleotide) for treating infertility or PCOS, and it should not be recommended. The provided evidence contains no studies, guidelines, or drug labels addressing NMN supplementation in this context. Instead, established evidence-based treatments with proven efficacy should be prioritized.

Evidence-Based Treatment Algorithm for PCOS-Related Infertility

First-Line: Lifestyle Modification (Mandatory Foundation)

All women with PCOS and infertility must begin with structured lifestyle intervention regardless of body weight. 1, 2

• Target 5-10% weight loss through combined diet, exercise, and behavioral strategies 1, 2, 3
• Create an energy deficit of 500-750 kcal/day with total intake of 1,200-1,500 kcal/day, adjusted for individual needs 1, 2
• Even 5% weight loss significantly improves ovulation rates and pregnancy outcomes 1, 3
• Perform at least 250 minutes/week of moderate-intensity activity or 150 minutes/week of vigorous activity, plus muscle-strengthening exercises on 2 non-consecutive days per week 3
• Exercise shows positive effects even without weight loss 4

Second-Line: Pharmacological Ovulation Induction

After lifestyle modification, clomiphene citrate is the first-line pharmacological treatment with the strongest evidence. 1, 2, 5, 6, 7

• Approximately 80% of PCOS patients ovulate on clomiphene citrate, and 50% of those who ovulate will conceive 1, 2
• Clomiphene citrate remains first-line in the absence of other male or female infertility factors 5, 6, 7
• If clomiphene fails, use low-dose gonadotropin therapy to minimize ovarian hyperstimulation risk 2, 5, 6
• Letrozole is an alternative option, though evidence comparing it to clomiphene is still evolving 5, 6

Adjunctive Metabolic Management

Screen for metabolic abnormalities before any ovulation induction. 1, 2, 3

• Perform 2-hour oral glucose tolerance test with 75-gram glucose load 3
• Obtain fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 2, 3
• Calculate BMI and waist-hip ratio to assess metabolic risk 1, 2
• Check TSH to exclude thyroid disease 3
• Measure prolactin to exclude hyperprolactinemia 3

Add metformin when insulin resistance or glucose intolerance is documented, or when lifestyle modifications alone are insufficient. 2, 3

• Metformin (500-2000 mg daily) improves insulin sensitivity and decreases circulating androgens 2, 3
• Metformin improves glucose tolerance over time and tends to decrease weight 3
• Metformin is superior to thiazolidinediones, which increase weight and have less favorable risk-benefit profiles 3
• Use of metformin solely for infertility is not recommended in absence of metabolic abnormality 7

Emerging Adjunctive Therapies

Myo-inositol shows promise as an alternative or adjunctive treatment, though more research is needed for definitive recommendations. 5, 7, 8, 9

• Myo-inositol 4000 mg/day plus folic acid 400 μg/day improved ovulation rates (70% restored ovulation) and achieved pregnancy rates of 15.1% in observational studies 8, 9
• Testosterone levels decreased from 96.6 ng/mL to 43.3 ng/mL and progesterone increased from 2.1 ng/mL to 12.3 ng/mL after 12 weeks of treatment 8, 9
• In IVF protocols, myo-inositol improved oocyte quality, fertilization rates, and embryo quality while reducing hyperstimulation risk 8
• Pregnancy rates with myo-inositol are at least equivalent or superior to those reported with metformin 8, 9

GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions. 2, 3

• Consider GLP-1 agonists if lifestyle modifications plus metformin prove insufficient after 3-6 months 3
• Particularly valuable for PCOS patients with BMI ≥27 with comorbidities or ≥30 without comorbidities 3

Third-Line: Surgical or Assisted Reproductive Technologies

Reserve IVF/ICSI or laparoscopic ovarian drilling for treatment failures or when other infertility factors are present. 5, 6, 7

• Laparoscopic ovarian drilling is an option when medical treatment fails 5, 7
• IVF/ICSI is recommended as third-line treatment or in the presence of other infertility factors 6, 7

Critical Pitfalls to Avoid

• Do not postpone metabolic screening even in normal-weight PCOS patients 2, 3
• For women with BMI <18.5 kg/m², postpone ovulation induction until BMI reaches ≥18.5 kg/m² 1
• Do not exceed recommended clomiphene dosage and duration 2
• Recognize that ethnic groups at high cardiometabolic risk (Asian, Hispanic, South Asian) require ethnic-specific BMI and waist circumference categories to guide treatment intensity 2, 3
• Address weight-related stigma, negative body image, and low self-esteem when discussing weight management 3

Why NMN Is Not Recommended

The absence of any guideline, drug label, or research evidence addressing NMN in PCOS or infertility means there is no basis for its use. The evidence provided focuses on established treatments with proven efficacy for morbidity, mortality, and quality of life outcomes. Stick with evidence-based interventions that have demonstrated benefit in randomized controlled trials and are endorsed by major professional societies.