Noninvasive metabolomic profiling of embryo culture media using proton nuclear magnetic resonance correlates with reproductive potential of embryos in women undergoing in vitro fertilization

Objective

To identify biomarkers associated with reproductive outcome using proton nuclear magnetic resonance (¹H NMR) metabolomic profiling of embryo culture media.

Design

Retrospective study.

Setting

An academic assisted reproductive technology (ART) program; a university research center.

Patient(s)

Women undergoing ART treatment.

Intervention(s)

Spent media samples from embryos that resulted in pregnancy and delivery (n = 17) and samples (n = 17) from embryos that failed to implant were individually collected on day 3, and evaluated using ¹H NMR spectroscopy. The spectra obtained were quantified by integrating six biomarker signals in the aliphatic region after baseline subtraction. Using a multivariate analysis, a model that calculates a viability index for each spectrum was developed. Sensitivity and specificity of predicting pregnancy (described as implantation and delivery) were calculated.

Main Outcome Measure(s)

The ¹H NMR metabolomic profile of embryo culture media and embryo viability.

Result(s)

Glutamate concentrations determined by ¹H NMR were significantly higher in spent culture media of embryos that resulted in pregnancy and delivery compared to those that failed to implant. Similarly, viability indices calculated by ¹H NMR using the weighted coefficients of glutamate and alanine/lactate ratio quantities were higher for embryos that implanted and resulted in a delivery. Proton NMR spectroscopy predicted viability of individual embryos with a sensitivity of 88.2% and a specificity of 88.2%.

Conclusion(s)

Metabolomic profile of spent embryo culture media using ¹H NMR correlates with the reproductive potential of embryos.

Key Words: Metabolomics, proton NMR, spectroscopy, embryo viability, reproductive potential, culture media, IVF