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

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.

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