Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.

Livia Z Yanez,Renee A Reijo Pera,Barry B Behr,David B Camarillo,Jinnuo Han

doi:10.1038/ncomms10809

Livia Z Yanez, Renee A Reijo Pera + Show 3 more

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https://doi.org/10.1038/ncomms10809

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Abstract

The causes of embryonic arrest during pre-implantation development are poorly understood. 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. 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. 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. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. 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.

Highlights

The causes of embryonic arrest during pre-implantation development are poorly understood
We show that patterns of gene expression found in non-viable embryos may affect cortical granule release and zona-hardening, which helps to explain the link between embryo viability and mechanical properties
A total of 89 two-pronuclear (2PN)-stage human zygotes from successful in vitro fertilization (IVF) cycles were thawed. We measured their mechanical parameters within 3 h after thawing, and tracked their development over 5–6 days using a time-lapse microscope (Eeva System from Auxogyn), with images taken every 5 min

Summary

Introduction

The causes of embryonic arrest during pre-implantation development are poorly understood. 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] These criteria are highly subjective, and their predictive value is controversial[11]. Some studies have begun to explore differences at the level of transcription between high- and poor-quality oocytes by inferring quality from maternal age[12,13] or ploidy[14] These measures of oocyte quality can only identify a subpopulation of all non-viable oocytes because chromosomal abnormalities can arise after this stage, and maternal age is not a perfect predictor of viability. Embryo and oocyte stiffnesses have been correlated to pregnancy in humans, and to maternal age in mouse, indicating that there may be a link between mechanics and viability[21,22,23]

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