Understanding why some IVF embryos suddenly stop growing

New research may help solve the medical mystery of why many in vitro fertilization (IVF) embryos fail to fully develop. A study published June 30 in PLOS Biology revealed metabolic and genetic changes in embryos with arrested development, which typically stop progressing within the first five to six days after fertilization.

On average, 50 percent to 70 percent of IVF embryos undergo arrested development. Understanding why embryos arrest could result in future technology that reverses or prevents it. While pro-life medical experts are encouraged by the study’s approach to human embryo research, they caution against these findings being used to bring arrested embryos back to life.

The researchers examined 23 arrested embryos obtained with consent from women receiving IVF treatment. While some previous studies suggested chromosomal abnormalities contributed to their paused growth, this one found the same rate of chromosomal abnormalities in the arrested embryos as in healthy ones.

The researchers, led by Andrew Hutchins at Southern University of Science and Technology in Shenzhen, China, classified the arrested embryos into three distinct groups based on gene expression.

The first group failed to transition control of gene transcription from the mother, a crucial stage in their development termed maternal-to-zygote transition (MZT). The second and third groups completed MZT, but exhibited decreased expression of several genes critical to further embryonic development. The second group had lower levels of a key metabolic pathway, oxidative phosphorylation, than did the third group.

Hutchins and his colleagues also experimented with reactivating arrested embryos from groups two and three using resveratrol, a molecule shown to affect embryo development. They found that more than half of those embryos recommenced growth after resveratrol treatment. Only three embryos made it to the blastocyst stage, when the embryo is five to six days post-fertilization and ready to be implanted into the mother’s uterus. “It appears to be possible to overcome this arrested state for some embryos, but much more work will be needed to determine the best strategy for doing so,” said Hutchins in a PLOS Biology news release.

James Sherley, an adult stem cell researcher and associate scholar at the pro-life Charlotte Lozier Institute, said he thinks the study was performed ethically. Sherley, when evaluating whether a research study is morally sound, first asks if any person is being injured during the process or after it. As the study’s authors outlined in detail, the embryos were effectively dead, thereby confirming that no human life was unnecessarily destroyed. Sherley next asks if the intent is good. Because the goal of IVF is procreation, he sees the study’s aims to increase the odds of IVF success as a moral good. “This is an example of what we want to see in embryo research,” he said.

Sherley did raise a concern about one aspect of the study: The RNA sequencing data used to compare arrested embryos to normal ones was compiled at the cost of human life. Human embryos donated from IVF clinics were manipulated to obtain genetic information, then ultimately destroyed.

Dr. John Gordon, owner of Southeastern Center for Fertility and Reproductive Surgery in Knoxville, Tenn., and a member of the Christian Medical and Dental Associations, said it’s common practice for IVF clinics to discard arrested embryos. Instead of placing these babies into biological waste, however, his clinic sends them to Sacred Heart Guardians and Shelter in Eagan, Minn., where they receive a burial ceremony.

Gordon doesn’t see the use of arrested embryos in biomedical research as morally problematic, either, but he does question the authors’ experiment to reactivate them. He believes there is likely a reason why some embryos arrest. Reactivating them could come with a host of unforeseen problems. 

“Medicine is full of well-meaning interventions that have resulted in disaster,” said Gordon. He illustrated this point with an example: the use of diethylstilbestrol (DES), a synthetic estrogen, to prevent miscarriage and other pregnancy complications. Broadly prescribed to American women for over 30 years, prenatal DES exposure was eventually linked to cervical cancer by researchers in 1971. Similarly, Gordon argued it would be almost impossible to assure IVF patients that the use of arrested embryos, if someday a technology existed to coax them to keep growing, was completely safe.

Meanwhile, some religious faiths, including the Roman Catholic Church, oppose IVF altogether. In 2008, the Vatican called the existence of frozen embryos a “grave injustice.”

“If we say life begins at conception … what we say about abortion applies both to the baby in the womb and to the embryo in the petri dish,” Paige Cunningham of The Center for Bioethics & Human Dignity told WORLD in 2017.

While Sherley shares Gordon’s concern about reviving arrested embryos, he doesn’t think the researchers necessarily intend to do so. Instead, he suspects they want to determine how to prevent arrested development from happening in the first place. “It is important to emphasize that the authors of this report did not speculate on either potential strategy, prevention or reversal,” he said.

If researchers move in the direction of developing a preventative treatment for arrested embryos, Sherley thinks this would be an exciting step forward in IVF technology.