Assisted reproductive technology like in vitro fertilization (IVF) is a critical tool for people affected by infertility. Embryologists commonly use morphological embryo grading methods as a component of IVF to determine the best-quality embryo for implantation, but these techniques lack accuracy and precision. The development of a minimally invasive, low-risk biomarker for embryonic growth would represent a significant improvement for the field.
For this reason, Yagi et al. (2016) evaluated changes in free fatty acid (FFA) in IVF embryonic culture medium in relation to embryo growth.1 They applied liquid chromatography–high resolution mass spectrometry (LC-HRMS) and metabolomics, harnessing an LTQ Orbitrap XL mass spectrometer and Qual Browser software revision 2.0 (both Thermo Scientific) for this purpose. This is the first application of LC-HRMS as a tool for assisted reproductive technology.
The team reported a significant change in FFA 22:6/DHA, which was lower in the good-growth group as compared with the poor-growth group. They also observed slightly lower values for other essential FFAs (FFAs 18:2/linoleic acid, 18:3/α-linolenic acid and 20:4/arachidonic acid), but these values were not statistically significant. They found no difference for the nonessential FFAs (FFAs 16:0/palmitic acid and 18:1/oleic acid).
The researchers note that essential FFAs must be acquired through consumption and that, for IVF embryos, the source of essential FFAs is the culture medium. Since the embryo must mature from one single cell to a 200–300 cell blastocyst, it requires significant consumption of lipids to build these cell membranes, potentially explaining the lower essential FFA values in the leftover culture medium from good-quality mature embryos.
The limitations of this study include the small number of samples and the semi-quantitative nature of LC-HRMS. The team calls for further studies with more samples as well as the application of liquid chromatography–tandem mass spectrometry (LC-MS/MS), with internal standards for verification purposes. However, since this study relies on relative change rather than absolute values, the semi-quantitative approach is also a benefit because it highlights the simplicity of the method.
In sum, Yagi et al. propose LC-HRMS-assisted IVF as a powerful tool for evaluating embryonic growth without risking the embryo itself. They note the method’s particular value for embryologists selecting among several embryos with similar morphological grades. They recommend the creation of a metabolomic grading system including FFAs, amino acids, glucose and other metabolic compounds as biomarkers for good embryonic growth.
1 Yagi, A., et al. (2016) “A fatty acid profiling method using liquid chromatography–high resolution mass spectrometry for improvement of assisted reproductive technology,” Clinica Chimica Acta, 456 (pp. 100–106).