Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study

Abstract

Objective: To determine if metabolomic profiling of embryonic development was associated with implantation rates in IVF.

Design: Prospective blinded.

Setting: University-affiliated assisted reproductive technology program.

Patient(s): Unselected assisted reproductive technology population.

Intervention(s): None.

Main outcome measure(s): Raman-based biospectroscopic metabolomic profiling of spent culture media and delivery rates.

Results: Forty-one spent media samples from 19 patients with known reproductive potential (0 or 100% delivery rates of each embryo that implanted) were evaluated. Raman-based metabolomic profiling was used to calculate a viability index for each sample. On day 3, the spent media of embryos with proven reproductive potential (n = 33) demonstrated higher viability indices (0.875 +/- 0.12) than those that failed to implant (0.56 +/- 0.09). Similar findings were present in spent media from embryos transferred on day 5 (n = 8) (-0.40 +/- -0.21 vs. -0.81 +/- -0.08). Receiver operating characteristic curve analyses were used to select thresholds with the greatest ability to discriminate outcomes. Overall diagnostic accuracy for predicting delivery or a failed implantation was 80.5%.

Conclusions: There is a clear relationship between the reproductive potential of human embryos and their modification of their culture media as detected by Raman biospectroscopy-based metabolomic profiling. This technology offers great potential for development as a tool to allow rapid noninvasive assessment of embryonic reproductive potential before transfer.