Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study
Received 11 February 2007; received in revised form 20 November 2007; accepted 20 November 2007. published online 18 February 2008.
Objective
To determine if metabolomic profiling of embryonic development was associated with implantation rates in IVF.
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.
aReproductive Medicine Associates of New Jersey, Morristown, New Jersey; Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ–Robert Wood Johnson Medical School, New Brunswick, New Jersey
bDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
cDepartment of Chemistry, McGill University, Montreal, Quebec, Canada
Reprint requests: David H. Burns, Ph.D., Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal QC H3A 2K6, Canada (FAX: 514-398-3797).
One of the authors, D.B., has an equity interest in the company developing this technology for clinical application (Molecular Biometrics, LLC). Three authors, R.S., E.S., and D.S., serve on a scientific advisory board of Molecular Biometrics.