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 ((1)H NMR) metabolomic profiling of embryo culture media.


METHODS
Retrospective study.


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


METHODS
Women undergoing ART treatment.


METHODS
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 (1)H 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.


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


RESULTS
Glutamate concentrations determined by (1)H 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 (1)H 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%.


CONCLUSIONS
Metabolomic profile of spent embryo culture media using (1)H NMR correlates with the reproductive potential of embryos.
Seli
Emre
E
Department of Obstetrics, Yale University School of Medicine, New Haven, Connecticut 06511, USA. emre.seli@yale.edu
Botros
Lucy
L
Sakkas
Denny
D
Burns
David H
DH
D015415:Biomarkers / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism*; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D050498:Live Birth; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D018873:Pregnancy Rate; D011522:Protons; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D015415:Biomarkers; D003470:Culture Media; D011522:Protons