Studying embryo development by novel microscopy techniques for improving IVF screening

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In vitro fertilisation (IVF) has been used for ~40 years but it remains an inefficient procedure (only ~26% success rate) and is expensive. Among the most common causes of failure are the embryos having the wrong number of chromosomes (termed 'aneuploidy') and embryos that that are not metabolising at the correct rate - these are difficult to determine without causing harm to the embryo. To improve screening and diagnosis for competent eggs/embryos the technology should be able to provide objective information of chromosome content and metabolic rate, but must also be non-invasive, label-free and non-destructive. Current methods mostly rely on imaging morphology alone, which by itself is an insufficient marker of the health of the developing embryo. Hence the overarching goal of this project is to address this and improve the efficiency of IVF. The project aims to develop methodologies to evaluate egg/embryo health and study early embryo development in order to ultimately improve outcomes for IVF patients. However, in order to perform such studies non-invasive and non-destructive technologies are needed. Optical technologies can be non-invasive but most current methods rely on use of fluorescent labels or dyes for visualisation. Furthermore, conventional imaging with confocal microscopy causes light-toxicity. Light sheet microscopy is an emerging novel microscopy technique that can provide damage-free rapid 3D visualisation. In our group we have recently developed label-free light sheet microscopy using low-energy near infrared light and two-photon imaging. In this project we will use this approach to study aneuploidy and metabolism in a mouse IVF model, developing ways of extracting the most information for the least light input. Development of image analysis approaches will also aid the rapid screening of eggs, sperm and embryos. These approaches will then be applied to human samples under ethical approval.