Fertility and Sterility
Volume 90, Issue 1 , Pages 77-83, July 2008

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

  • Richard Scott, M.D.

      Affiliations

    • Reproductive 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
    • ,
  • Emre Seli, M.D.

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Kathy Miller, B.S.

      Affiliations

    • Reproductive 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
    • ,
  • Denny Sakkas, Ph.D.

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Katherine Scott, B.S.

      Affiliations

    • Reproductive 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
    • ,
  • David H. Burns, Ph.D.

      Affiliations

    • Department of Chemistry, McGill University, Montreal, Quebec, Canada
    • Corresponding Author InformationReprint requests: David H. Burns, Ph.D., Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal QC H3A 2K6, Canada (FAX: 514-398-3797).

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.

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.

Key Words: Implantation, Raman, biospectroscopy, metabolomics, embryo quality, reproductive potential, culture media, IVF, delivery rate

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 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.

PII: S0015-0282(07)04123-4

doi:10.1016/j.fertnstert.2007.11.058

Fertility and Sterility
Volume 90, Issue 1 , Pages 77-83, July 2008

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