Scientists identify chromosomal fate of embryos at earliest stage of human development

Scientists identify chromosomal fate of embryos at earliest stage of human development

Scientists identify chromosomal fate of embryos at earliest stage of human development

Prediction of chromosomal abnormalities in embryos could improve IVF success rates for women around the world

Chromosomal abnormalities in human embryos created for in vitro fertilisation (IVF), can be predicted within the first 30 hours of development according to recent research published in Nature Communications.

This discovery could improve the rate of success for IVF, which hovers at around 30 to 35 per cent. It is estimated that between 50 to 80 per cent of embryos created for IVF have a chromosomal abnormality and typically do not develop into a pregnancy, instead resulting in miscarriage.

Key findings of the research, which was conducted by Shawn Chavez and colleagues at Stanford University and analysed at Oregon Health & Science University, showed that by looking at the duration of the first mitotic phase – a short period in the cell cycle – chromosomally normal versus abnormal embryos can be identified up to approximately the 8-cell stage. Most importantly, by looking at a single-cell level, the researchers were able to correlate the chromosomal make-up of an embryo to a subset of 12 genes that are activated prior to the first cell division. These genes likely came from the gametes – the eggs or sperm – and can be used to predict whether an embryo is chromosomally normal or abnormal at the earliest stage of human development.

The findings could enable clinicians and embryologists to identify the healthiest embryo for implantation more quickly and reduce the amount of time an embryo is cultured in the laboratory prior to transfer. Embryos typically need to be implanted within three to five days of creation, which has created a challenge for the IVF field because chromosomal abnormalities may not be identified until day five or six.

“Many couples are choosing to have children later in life, and this trend is only going to continue,” said Chavez. “A failed IVF attempt takes an emotional toll on a woman who is anticipating a pregnancy as well as a financial toll on families, with a single IVF treatment costing thousands and thousands of dollars per cycle. Our findings also bring hope to couples who are struggling to start a family and wish to avoid the selection and transfer of embryos with unknown or poor potential for implantation.”

The study took advantage of significant advances in both single-cell genetic profiling and non-invasive imaging, and is the first to combine analysis of complete chromosomal constitution, high-throughput single-cell gene expression and time-lapse imaging simultaneously in the same human embryo.

This research was conducted using 117 human zygotes originating from 19 couples, with an average maternal age of 33.7±4.3 years. The large set of human embryos was obtained from previous IVF cycles with written informed consent from the Stanford University RENEW Biobank.

Researchers say future studies should also focus on the zygote as a potential source of non-invasive biomarkers that can prospectively predict chromosomal status and avoid potential detriment(s) of prolonged embryo culture.

Reference

Vera-Rodriguez, M., Chavez, S.L., Rubio, C., et al. (2015) Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis. Nature Communications 6, 7601. doi: 10.1038/ncomms8601

Source: Oregon Health & Science University

www.ohsu.edu

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