However, these criteria are highly subjective, and their predictive value is controversial 11. In humans, various oocyte morphological characteristics 6 have been correlated with embryo development and implantation potential, including zona thickness 7, granularity 8, perivitelline space 9 and oocyte shape 10.

The major wave of transcription involved in EGA is observed at the one-cell zygote to the two-cell stage in mouse 4 and the four- to eight-cell stage in humans 5. Before EGA no transcription occurs, and so the very first steps of embryogenesis are controlled exclusively by maternal information inherited from the oocyte 1, 2, 3. It has been suggested that an embryo’s fate is determined very early in development, before embryonic genome activation (EGA), or even before fertilization 1, 2, 3. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. The causes of embryonic arrest during pre-implantation development are poorly understood.

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