Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Effect of age and NMN supplementation during rescue in vitro maturation on human oocyte meiotic architecture (143837)

Denise Lin 1 , Ananya Vuyyuru 1 , Lindsay E Wu 2 , Bettina P Mihalas 1 , Robert B Gilchrist 1
  1. Discipline of Women’s Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
  2. School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia

Background

Age-associated decline in oocyte quality is a major contributor to reduced female fertility and is characterised by spindle abnormalities and cohesion loss, contributing to increased aneuploidy. The nicotinamide adenine dinucleotide precursor nicotinamide mononucleotide (NMN) improves age-associated oocyte defects in animal models. However, its effects on human oocytes lacking metabolically supportive cumulus cells during rescue in vitro maturation (r-IVM) remain unclear. This study investigates the impact of NMN supplementation on meiotic architecture in human oocytes during r-IVM across reproductive age.

Methods

Discarded naked human germinal vesicle (GV, n=231) and metaphase I (MI, n=73) oocytes from patients undergoing intracytoplasmic sperm injection (18–43 years) underwent r-IVM for 24 hours ± NMN. Oocytes were immunostained for α-tubulin (microtubules), CENP-C (kinetochores) and SGO2 (shugoshin-2), with chromosomes counterstained using DAPI. Germinal vesicle breakdown (GVBD), MII maturation rates, spindle length and width, interkinetochore distance (IKD) and SGO2 localisation were quantified.

Results

NMN did not significantly affect oocyte maturation. GVBD occurred in 73% of control and 83% of NMN-treated oocytes (p=0.28), with no significant age effect. GV-to-MII and MI-to-MII maturation rates were not significantly affected by NMN supplementation or age (53% vs 53% and 87% vs 63% in control and NMN-treated oocytes, respectively). Spindle length was unaffected by NMN or age; however, NMN significantly reduced spindle width (6.68 vs 6.03 μm, p=0.03), with no age-related trend. IKD increased with reproductive age (p=0.02) but was unaffected by NMN. IKD was increased in the absence of a SGO2 bridge (p<0.0001), while NMN did not alter SGO2 localisation.

Conclusion

Rescue-IVM with NMN had modest effects on meiotic architecture, selectively narrowing spindle width. Further studies are needed to determine whether the absence of cumulus cells during r-IVM limited the efficacy of NMN and whether these structural changes translate to reduced aneuploidy with reproductive age.