Genetic Screening May Endanger Fetuses

Screening unborn children for genetic defects appears to reduce the chances of a healthy pregnancy and live birth, new research suggests.

The findings, published in the current issue of the New England Journal of Medicine, suggest that checking embryos before using them in in vitro fertilization, and implanting the ones that seem more genetically and structurally healthy, may actually lead to lower rates of pregnancy.

Ironically, this technique -- known as preimplantation genetic screening, or PGS -- is aimed at finding the healthiest embryos. Most experts thought it would not change the odds for women trying to get pregnant, and the technique has even become routine for women over 35 who wish to get pregnant.

"In contrast to what would be expected or what many people are saying who are currently offering this technique, PGS actually decreases pregnancy chances in these groups of women who are 35 years or older," said Sjoerd Repping, director of the IVF lab at the Academic Medical Center in Amsterdam and one of the main authors of the study.

Many doctors expressed surprise at the findings.

"This is the first study that suggests that not only does it not improve the outcome, but it may actually be harmful," said Dr. Steven Ory, president of the American Society for Reproductive Medicine.

"I'm a little bit surprised to see a decreased rate," said Dr. Marcelle Cedars, director of the division of reproductive endocrinology and infertility at the University of California at San Francisco. "But I'm not really surprised to see an absence of a positive effect."

Reducing Reproductive Chances

PGS is often done as a part of in vitro fertilization.

In IVF, a sperm and an egg are joined together outside a woman's body. As the newly formed embryo grows, it splits into more and more cells.

PGS involves taking a single cell from the growing embryo and, in this study, looking to see if it has the proper complement of two of each chromosome -- one from mom and one from dad.

Embryos that fit the bill are then implanted in the mother's womb.

Researchers in Amsterdam wanted to study the effect of this screen on rates of pregnancy in women over 35, dubbed "advanced maternal age." About half of all women undergoing IVF fit into this category.

"As women got older, we would see a reduction in their pregnancy rate and that we could tie this to the quality of the egg," said Dr. William Gibbons, a current IVF practitioner and former president of the Society for Assisted Reproductive Technology.

In women 35 and older, an abnormal number of chromosomes in their eggs is thought to be a leading cause of miscarriage. It stands to reason, then, that implanting embryos that have been checked and do not have this problem should lead to more full-term pregnancies.

In this study, conducted by researchers in Amsterdam, 206 women had their embryos screened before they were implanted for IVF treatment, and 202 women underwent IVF without having their embryos screened.

When the two groups were compared, both were found to have the same rate of miscarriage.

The differences between the groups came from the number of women who had viable pregnancies at 12 weeks after treatment. In the control group, it was 37 percent, and in the group whose embryos were screened, it was only 25 percent.

As for the number of women who gave birth to live babies, the rates were 24 percent in the women whose embryos were screened, compared with 35 percent in women who didn't have the screening.

Mysteries Remain

There are many potential explanations for why the pregnancy and birth rate are lower after screening.

One is the physical impact of taking out a part of the embryo in order to screen it, or doing a biopsy.

"If you do a biopsy from an embryo -- you have to remove a single cell to know about the genetic makeup -- that may be detrimental to the embryo's ability to implant," said Repping.

"The current technology for the biopsy can slow embryo growth and hinder implantation, by about 10 percent or so," said Dr. Robert Stillman, medical director at Shady Grove Fertility Center, the largest IVF clinic in the country. "There's a risk to a biopsy, whether you're doing it in the breast or the lung or an embryo."

Another reason the screen reduced pregnancy rates may be mosaicism, which occurs when "one cell is not like the rest of the embryo, like a mosaic tile," according to Stillman.

"I think the fact that one cell from an embryo is not representative of all cells from an embryo is very important," Repping said. Mosaicism could lead scientists to implant an embryo in which one cell tested normal but the remaining embryo was unhealthy.

Finally, many experts point to the fact that the limits of the current technology allow the screen to check only eight of the 23 pairs of human chromosomes. Abnormalities present in one of the other 15 pairs could have considerable sway on the chances of pregnancy.

"Next year or the year after, we will be able to screen all 23 chromosome pairs, and we can do it with safer biopsy techniques," Stillman said.

Even then, some experts don't think that genetics can tell the whole story behind which women will get pregnant using these therapies.

Cedars of UCSF recommends that women talk to their doctors about what the data means for them. Her advice is "to be cautious and to not too quickly look for the magic bullet."

"Technology does not always have what we wish it did."