Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity

Objective: To determine whether fluorescence lifetime imaging microscopy (FLIM) detects differences in metabolic state among cumulus cell samples and whether their metabolic state is associated with patient age, body mass index (BMI), and antimullerian hormone (AMH) level and maturity of the oocyte. Design: Prospective observational study. Setting: Academic laboratory. Patient(s): Cumulus cell (CC) clusters from cumulus-oocyte complexes were collected from patients undergoing assisted reproductive technology treatment after oocyte retrieval and vitrified. Intervention(s): Cumulus cell metabolism was assessed using FLIM to measure autofluorescence of nicotinamide adenine (phosphate) dinucleotide and flavine adenine dinucleotide, endogenous coenzymes essential for cellular respiration and glycolysis. Patient age, BMI, and AMH level and the maturity of the corresponding oocytes were recorded. Main Outcome Measure(s): Quantitative information from FLIM was obtained regarding metabolite concentrations from fluorescence intensity and metabolite enzyme engagement from fluorescence lifetimes. Associations were investigated between each FLIM parameter and oocyte maturity and patient age, BMI, and AMH. Variance between CC clusters within and between patients was determined. Result(s): Of 619 CC clusters from 193 patients, 90 were associated with immature oocytes and 505 with metaphase II oocytes. FLIM enabled quantitative measurements of the metabolic state of CC clusters. These parameters were significantly correlated with patient age and AMH independently, but not with BMI. Cumulus cell nicotinamide adenine (phosphate) dinucleotide FLIM parameters and redox ratio were significantly associated with maturity of the enclosed oocyte. Conclusion(s): FLIM detects variations in the metabolic state of CCs, showing a greater variance among clusters from each patient than between patients. Fluorescence lifetime imaging microscopy can detect CC metabolic associations with patient age and AMH and variations between mature and immature oocytes, suggesting the potential utility of this technique to help identify superior oocytes. (C) 2021 by American Society for Reproductive Medicine.

Automated summary

Fluorescence lifetime imaging microscopy (FLIM) can accurately measure the metabolic state of cumulus cell clusters, with parameters significantly correlated with patient age and AMH levels but not with BMI. This technique may have potential value in identifying superior oocytes.