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IVF

What are the ethical issues? Researchers can screen embryos for a wider array of conditions, but they stress there are no guarantees.

By Pesach Benson, United With Israel

Until now, embryos conceived through in vitro fertilization could be screened for a limited number of rare genetic diseases, such as Tay-Sachs and cystic fibrosis.

However, new advances make it possible to screen for the likelihood of a wider array of diseases such as cancer, diabetes, heart disease and psychiatric disorders such as schizophrenia.

As part of the IVF cycle, women may have several eggs removed simultaneously to be fertilized in a laboratory. When parents have family histories for certain problematic genetic conditions, the embryos can be screened and ranked for the likelihood of carrying those diseases.

Doctors can advise prospective parents which embryos to choose before implanting them in the mother. Unused embryos can be frozen and saved for future treatment if necessary. That’s the simple story behind an average of 500,000 IVF babies delivered every year.

However, one key question needs addressing: Can screening actually reduce the probability that an embryo will develop one of those diseases?

That was the focus of a statistical analysis by a team of researchers led by Hebrew University Professors Shai Carmi and Or Zuk, along with Professor Todd Lencz at New York’s Feinstein Institutes for Medical Research. Their findings were published Tuesday in eLife.

For decades, couples whose offspring were at risk of developing a devastating childhood disease had the option to screen the genetic makeup of their embryos. In those cases, only a single mutation on a specific gene is responsible for the disease, and consequently, these diseases are known as monogenic.

However, most adult diseases are not monogenic, but rather polygenic – affected by a large number, sometimes thousands, of different genes and variants, each having a small effect on the risk of developing a particular disease.

Polygenic risk scores combine genetic variants in these numerous genes to estimate the risk of an individual. By now, already one company is taking advantage of polygenic risk scores to offer screening of embryos for polygenic diseases.

The Hebrew University and Feinstein Institute researchers analyzed scenarios where parents were provided with the risk scores of their embryos for one given disease. These parents were then faced with two selection strategies: to eliminate embryos with a particularly high score for an undesirable disease and then randomly choose one of the remaining embryos for implantation, or to simply select the embryo with the lowest predicted risk score.

The first strategy eliminates some ethical issues, because no single embryo is selected as the “best” of the group. However, the researchers showed this choice did not substantially reduce the risk of developing a disease. In fact, they found it was much better to select the embryo with the lowest risk score.

The team’s statistical analysis was further confirmed when they ran simulations for “virtual parents” based on real genomes from studies of Crohn’s disease and schizophrenia. The researchers stressed that screening embryos based on polygenic scores does not offer any guarantees about the health of the baby; it only reduces the risk.

Moreover, the achieved risk reduction may be smaller than expected — it depends on several factors such as the specific disease being screened, the ancestry of the parents, and their age.

“Given the complexities, we urge all stakeholders—clinicians, IVF patients, prospective parents, professional societies, and lawmakers—to keep our study results in mind and carefully consider the limitations of polygenic embryo screening, along with its ethical, legal, and social implications,” Carmi suggested.

“Overall, it’s imperative that the debate on polygenic embryo screening be a well-informed one,” concluded Carmi.

The scientists see their research going forward in two major directions. “The first will involve interviews with parents and clinicians to better understand their views on the use of risk scores when selecting embryos. The second is to consider the possibilities and outcomes when parents screen their embryos for more than one disease,” Lencz said.