Lab on a chip could improve the success of in vitro fertilisation
US researchers may have found a new way to assess the health of embryos produced by in vitro fertilisation (IVF), using a lab on a chip approach to measure their uptake of nutrients.
IVF procedures have a disappointingly low success rate - typically less than 25 per cent - because many embryos carry defects that prevent them successfully implanting into the uterus. Doctors currently try to spot healthy embryos by watching how they grow in the days before they are ready for implantation, and assessing the overall shape of the cells. But generally this only identifies embryos with gross defects.
Now, Todd Thorsen’s team at the Massachusetts Institute of Technology’s department of mechanical engineering have developed a microfluidic chip to measure the rate that mouse embryos consume three key nutrients, glucose, pyruvate and lactate. All three nutrients are substrates in a reaction catalysed by the embryo’s nitrite reductase enzyme NAD(P)H, which fluoresces in its reduced form. The amount of light produced indicates the rate that the nutrients are being used by the embryo.
Such postage stamp sized microfluidic devices are now standard technologies in molecular biology labs. But Thorsen’s team had to overcome three challenges - minimising the amount of fluid needed, developing an automated system for handling samples, and avoiding contamination with the oil used on the surface of embryo cultures to prevent evaporation and damage to the embryos.
Although the current study used mouse cells, Thorsen says the technique is relevant to human fertility research, and could be ready for use in human fertility clinics within about five years. ’We don’t foresee any difficulty in transitioning the work to human embryos, as the in vitro culture systems are quite similar,’ he told Chemistry World. ’First, we need to carry out validation experiments to demonstrate the link between the embryo metabolomics and successful pregnancies with the target embryos in mice and eventually in humans.’
Dmitri Papkovsky of University College Cork, Ireland, has carried out similar studies on embryo metabolism using microfluidic detectors to measure oxygen consumption. He says the metabolites used have not been shown to be good predictors of embryo development and that other research groups are studying more sophisticated arrays of biochemical markers. Nonetheless, he says, this research ’is a significant step forward in achieving the ultimate goal of performing quality control of embryos for IV’.
David Keefe, a fertility specialist at the University of South Florida, US, agrees that the method has potential. ’It promises to automate the most technically challenging part of IVF and embryo transfer, and therefore ultimately to rein in the runaway costs of fertility treatments. The rubber will meet the road when this technology enters clinical trials with human embryos, where the differences among embryos are likely to be quite subtle.’
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J P Urbanski et alAnal. Chem., 2008, DOI: 10.1021/ac8010473
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