Doctors question a test for IVF embryos

A recent study suggests that genetic testing of embryos may provide misleading information to families undergoing in vitro fertilization (IVF). Published in Human Reproduction last month, the study found that some women who decided to implant embryos that tested positive for genetic abnormalities later gave birth to healthy infants. The findings call into question the usual practice of discarding such embryos.

Fertility clinics offer preimplantation genetic testing for aneuploidy (a test known as PGT-A) to prospective mothers as a tool for eliminating embryos with chromosomal abnormalities. Embryos that display an irregular number of chromosomes at their stage of development are typically believed to be less likely to implant and grow once transferred to a woman’s uterus.

PGT-A testing has long been considered controversial. Because a small number of cells are taken from the embryo for testing, there’s a chance they do not represent the entire embryo. The testing process can introduce error, as test results are based on copies of the sampled cells. Test methods and technologies vary from clinic to clinic, with little evaluation of their accuracy.

The Human Reproduction study’s authors argue PGT-A screening leads to the unnecessary rejection of viable embryos. Pro-life medical experts, who object to such discarding of embryos, also worry about potential damage done to the embryo during testing.

The Centers for Disease Control and Prevention estimates 44 percent of embryos transferred in the United States in 2019 underwent preimplantation genetic testing. Many fertility clinics refuse to use embryos screened as abnormal. (Similarly, some doctors encourage women already pregnant to abort babies based solely on abnormal results from questionable blood tests.)

In last month’s study, 144 embryos considered abnormal based on PGT-A testing were moved to the Center for Human Reproduction in New York City from fertility clinics that had refused to use them. Specialist Norbert Gleicher and his colleagues started transferring these embryos to fertility clients in 2014. A little over 70 percent of the embryos had one or two chromosomal abnormalities, just over 20 percent had three or more, and the remainder were considered “undiagnosed” because of inconclusive test results. The 50 women in the study were on average 41 years old. Most were given a poor prognosis, which at their age meant a less than 5 percent chance of pregnancy. Ultimately, the embryo transfers resulted in eight live births and 11 miscarriages.

While that may sound like a low success rate, the alternative option for these women was no shot at IVF and zero births or miscarriages. Gleicher said in an email statement provided to The New York Times, “Ask women what they prefer: A risk of miscarriage or no chance of having a baby at all. The answer will be clear.”

Gleicher has argued against the use of PGT-A testing in IVF for years, contending that its high false-positive rate leads to the destruction of healthy embryos. Some types of aneuploidy (the broad term for abnormal numbers of chromosome copies) provide a definite diagnosis: For example, a positive test for trisomy 21 means a baby will have Down syndrome. But some evidence suggests other types of aneuploidies can self-correct.

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, doesn’t offer PGT-A testing to his patients. In many instances, he said, the PGT-A test results aren’t informative enough to say definitively that the embryo will not implant or that the baby will have a genetic disorder. The test relies on a biopsy of cells that later develop into the placenta, and it assumes that any genetic problems in those cells will also be present in other cells that develop into the baby. But Gordon pointed out we don’t know if that’s true: It’s possible the abnormal cells are shunted into the placenta as a self-correcting mechanism, which would help explain why some babies are born healthy despite an abnormal PGT-A test. (Two studies done in mouse models indicate a higher rate of chromosomal abnormalities in the placenta-forming group of cells.)

PGT-A tests also risk damaging or destroying the embryo, Gordon said. During the biopsy process necessary for the test, clinic workers use a laser to create an opening in an embryo about five to seven days after fertilization. As they tease out a few cells for DNA testing, the embryo transforms in shape from a robust beach ball to a shriveled blob. Some evidence suggests this process can damage the embryo’s development.

Gordon previously worked for a large fertility clinic in Northern Virginia that routinely offered genetic screening tests. During his 20 years there, his ethical concerns about these tests grew. He recalled seeing a patient who was over 40 and whose two embryos “looked terrible,” according to the embryologist. Gordon transferred them anyway. To his surprise, the patient became pregnant and ultimately delivered healthy twins.

The case was a turning point for Gordon. While he and other IVF specialists could make predictions about an embryo’s chance of implanting, they couldn’t make guarantees. “The only way that you know the embryo’s not going to turn into a baby is by not putting it in,” he said.

James Sherley, an adult stem cell researcher and associate scholar at the pro-life Charlotte Lozier Institute, agrees with Gordon about some of the dangers posed to human life by PGT-A testing. He’s also optimistic about the technology’s potential as a diagnostic tool. But he noted that a diagnosis without a cure can lead some parents toward abortion.

“I understand the motivation to increase our technical ability,” Sherley said. “The problem is that it’s often ahead of our moral principles.”

Sherley is hopeful about the use of cutting-edge technology for good. He imagines a future in which PGT-A testing identifies a genetic disorder such as Klinefelter syndrome and doctors follow it up with a curative treatment—like a real-life version of Star Wars’ fictional healing liquid, bacta. “There can be a time [where] we learn how to fix problems in the single-cell embryo,” he said. “But the guiding principle is that we do everything we can to protect human life.”