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Study Raises Questions About Popular Genetic Test for ‘Abnormal’ Embryos

The test leads people undergoing in vitro fertilization to discard thousands of embryos each year. The new research found implanting some “abnormal” embryos resulted in healthy live births.

When they began their first two rounds of in vitro fertilization in 2015, Anna Dahlquist and her husband, Brian, took a common genetic test to determine the condition of the embryos they had created. The results were devastating: All 13 were “abnormal.”

The embryos sat frozen at their fertility clinic in Seattle for six years as the couple underwent round after grueling round of unsuccessful I.V.F. After three years, they had a healthy daughter, using an embryo that they had decided not to test.

Then, last year, they went to a new clinic — one that has questioned the reliability of the popular genetic test they took. The clinic implanted a round of the couple’s irregular embryos — two embryos with one chromosomal error and one with two errors. Last month, Ms. Dahlquist gave birth to a healthy baby boy.

“I was 39 when I made his embryo,” Ms. Dahlquist said. “And I was 46 when I became pregnant with him. That’s a long time and a lot of valuable years in both my child’s upbringing and my life.”

The genetic test, called preimplantation genetic testing for aneuploidy, or PGT-A, has, over the last two decades, become a standard add-on to already pricey I.V.F. procedures. But the test, which can cost anywhere from $4,000 to $10,000, has become controversial over the years as studies have cast doubt on whether it increases birthrates from I.V.F. at all. A growing number of scientists have questioned the widespread use of the test, which leads to tens of thousands of discarded embryos per year and causes many women to believe they may not be able to carry biological children.

A new study published last week details 50 patients who underwent transfers of abnormal embryos at the Center for Human Reproduction in New York City. (The Dahlquists had their abnormal embryos transferred to this clinic, since their local clinic would not implant them.) The study reported eight births after 57 transfer cycles of embryos with abnormal genetic testing results since 2015. Seven of the babies were born healthy. The average age of the women in the study was 41 years old.

The study is a follow-up to a 2015 study also led by the center that first showed that selected abnormal embryos could still be viable. Since then, other fertility clinics worldwide have also started to transfer such embryos.

The research was funded by the clinic and by the Foundation for Reproductive Medicine, a nonprofit research organization also based in New York.

The new study “supports concerns that I and others have had for several years now about the accuracy of these tests,” Josephine Johnston, a bioethicist and director of research at the Hastings Center who was not involved in the research, said by email. “The study strengthens the argument that PGT-A tests have been prematurely incorporated into fertility medicine and strongly suggests that these tests will have led patients to discard potentially viable embryos.”

But the new study also shows the limitations of transferring such embryos. A vast majority of the 144 embryos transferred by the group had only one or two chromosomal abnormalities, but the transfers led to 11 miscarriages in addition to the eight live births.

“There’s a lot of miscarriages in that ratio,” said Laura Hercher, director of student research at the Sarah Lawrence College genetic counseling program.

The PGT-A test is used to screen for aneuploidy, which is when an improper number of chromosomes — either too few or too many — is detected in sampled cells. An abnormal number of chromosomes can, in serious cases, lead to genetic disabilities, like Down syndrome. More often, the wrong number of chromosomes can lead to failed pregnancies, either by preventing embryos from implanting or by causing miscarriages.

But the problem with PGT-A, the authors of the study argue, is that it provides an incomplete picture that is often interpreted as a very definitive result. The test relies on sampling a handful of cells from the outer shell of the developing embryo and testing to see if each one has 23 pairs of chromosomes.

“The point of PGT was to select embryos that would give somebody a better chance of achieving pregnancy,” said Dr. David Barad, an OB-GYN at the Center for Human Reproduction and a co-author of the study. “But doing genetic testing doesn’t make embryos better, it just kind of gives us some idea of who they are.”

Though moving ahead with using these embryos with abnormalities may come with some risk, the authors of the new study, all of whom were connected to the clinic doing the transfers, argue that viable embryos are currently being disregarded, leaving many women to believe they have no other options to achieve a pregnancy.

“The miscarriage rate is roughly what one expects at such advanced age,” Dr. Norbert Gleicher, director of the clinic and a co-author of the study, said by email. He added: “Ask women what they prefer. A risk of miscarriage or no chance of having a baby at all. The answer will be clear.”

In one of the pregnancies in the study, the fetus was diagnosed with a heart defect in utero. The parents moved forward and had a live birth. After having surgery as a newborn, the baby is reportedly healthy. Dr. Gleicher said there was “no known connection whatsoever” between the birth defect and the chromosomal error.

A bigger study of outcomes would make clearer whether there is a risk of birth defects, Ms. Hercher said. But this outcome also speaks to the complex level of uncertainty that fertility providers will have to face — and properly educate their patients about — when it comes to the potential risks involved with using these embryos.

“We don’t really know what to tell them about the long term potential consequences to a child that’s born,” Ms. Hercher said. “Will there be an increased number of birth defects? Will we find that they have problems down the road? There’s a lot of ‘I don’t knows.'”

Irregular numbers of chromosomes are surprisingly common, especially as women get older. For women over 35, there’s roughly a 50 percent incidence of aneuploidy in embryos produced during I.V.F. that increases with age. As the fertilized egg divides and multiplies into cells, errors that occur down the line can be replicated. But the normal cells might have a competitive advantage over the abnormal cells, leading the vast majority of the cells in the embryo to still have the correct number of chromosomes. Or some of those incorrect cells may eventually self-correct.

Either way, the potential for this patchwork of cells means that any one picture of the embryo will be limited. A normal test result could miss irregular cells elsewhere, and one cell with the wrong number of chromosomes is enough to turn up abnormal results. By sampling just a small subset of cells at a very early stage in embryo development, PGT-A may cause some fertility clinics, wary of taking risks, to reject embryos that could lead to healthy pregnancies.

False positives are also a problem for women who don’t undergo I.V.F. On Tuesday, the Food and Drug Administration warned that noninvasive prenatal tests, which look for signs of genetic abnormalities in the fetus, could lead patients to make decisions about their pregnancies based on incorrect information.

Some researchers argue that PGT-A may still be useful for some people. For younger patients who produce more eggs, the test can help rank which embryos have the highest likelihood of succeeding, minimizing the number of procedures they have to undergo and pay for.

But the Dahlquists, who were told that the “abnormal” embryos they produced in their first two cycles of I.V.F. could not be used, believe more nuance needs to be communicated to patients so they can be empowered to weigh the risks and make informed decisions.

The fact that their fertility clinic would not allow potentially viable embryos to be used and forced them to wait six years to use them made her feel powerless, Ms. Dahlquist said. Few clinics will agree to transfer such embryos, and, at the time they took the test, the couple didn’t even know that was a possibility.

“I just feel like it’s unfair,” she added. “They really are ruining a lot of people’s chances.”

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