Genetic mishaps in early development cause nearly Half of embryo arrests in IVF

Scientists have conducted genetic testing on nearly 1,000 embryos, yielding a comprehensive analysis of embryo development during human in vitro fertilization. Their findings reveal that almost half of the studied embryos experienced developmental setbacks due to genetic anomalies in early development, hinting that adjustments in the IVF process could increase the chances of successful pregnancies. This unique dataset, derived from arrested embryos, also sheds new light on the enigmatic early stages of natural pregnancy.

Author Rajiv McCoy, an assistant professor of biology at Johns Hopkins University, suggested, “We believe that similar processes occur in natural conception, possibly contributing to the several-month average time it takes to become pregnant. What’s striking is that most of these developmental hiccups are not due to issues with egg formation but rather errors in cell divisions following fertilization. This suggests that altering IVF procedures might help mitigate these errors.”

The research is set to be published in Genome Medicine.

A time lapse clip of a common type of abnormal cell division where an embryo cleaves directly from a single-celled zygote into three (rather than two) cells. The new research shows such abnormal division is strongly associated with chromosome abnormalities and embryo arrest. Credit: Christian Ottolini

Researchers from Johns Hopkins and the London Women’s Clinic in the United Kingdom conducted a comparative study on IVF embryos, distinguishing those that failed to develop shortly after fertilization from those that thrived, with a focus on genetic disparities.

Typically, genetic testing is reserved for IVF embryos that progress, helping clinicians decide which one to transfer into the uterus. However, from a biological perspective, a comprehensive examination of all embryos is necessary to comprehend the factors contributing to their survival.

The study uncovered how certain embryos initiate proper growth with maternal genetic material guiding cell division, only to encounter setbacks when the embryo’s own genes take over.

In the realm of human cells, the standard count is 46 chromosomes, with 23 inherited from each parent. Remarkably, nonviable embryos commenced with the correct 46-chromosome set but experienced incorrect chromosome numbers during cell division.

Rajiv McCoy noted, “Initial discrepancies in chromosome count matter less because maternal mechanisms oversee early stages. Problems arise when the embryo’s genome activates.”

Human embryos exhibit notably high rates of chromosome gain and loss, termed aneuploidy, in their early development stages. IVF embryo screening has long explored aneuploidy’s role in human pregnancy loss. While aneuploidy is rare in many other species, these findings offer insights into why miscarriages and pregnancy losses are prevalent in humans.

McCoy stated, “Aneuploidy is a robust form of natural selection that occurs in every human generation. It might be inherent to human reproduction and development, but it holds implications for IVF. Over time, we aspire to enhance genetic testing and IVF outcomes.”

The researchers plan to conduct further investigations, examining specific cells from arrested embryos to trace the origins of chromosomes and determine if abnormal cell divisions are tied to maternal or paternal genetics. Additionally, they aim to explore whether factors like the chemical composition of the culture medium used for embryo growth can enhance their chances of survival.

Co-author Michael Summers emphasized, “Our understanding of the mechanisms behind embryo arrest could potentially lead to corrections. It’s possible that culture medium composition might hinder some embryos from developing, causing abnormal cell divisions associated with chromosome irregularities.”

Source: Johns Hopkins University

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