Cautions issued over prenatal genetic tests in IVF and for rare diseases

chromosomes-harvardExpectant parents, doctors, and regulators need to reconsider the rising use of gee-whiz genetic testing as  doubts emerge about popular blood screenings to detect rare prenatal disorders and a costly test relied on by couples undergoing in-vitro fertilization (IVF) treatment.

This is what the New York Times reported about what researchers have found about preimplantation genetic testing for aneuploidy, or PGT-A. It is an increasingly common screening in IVF and has led potential parents to discard embryos as unfeasible or unacceptable due to abnormalities to carry to term:

“PGT-A … has, over the last two decades, become a standard add-on to already pricey IVF 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 IVF 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 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.’”

The newspaper reported this key criticism of the test:

“[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 [structures, as shown in Harvard single-cell, color photo]. ‘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.’”

Researchers caution that embryos flagged by the PGT-A test and that prove viable to carry to term have risks — of miscarriage or of infants having abnormalities at birth, the newspaper reported. These can be the result, though, of conditions and circumstances — such as the mother’s age — that lead couples into the challenging, costly IVF process.

The PGT-A test, with its results presented without nuance and complete explanation, can derail complex choices about IVF embryos, especially if couples proceed with those now declined due to the PGA-T test, the New York Times reported, quoting experts, including Laura Hercher, director of student research at the Sarah Lawrence College genetic counseling program.

“We don’t really know what to tell them about the long-term potential consequences to a child that’s born. 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.’”

The New York Times article, by the way, reports on Anna and Brian Dahlquist, a couple undergoing IVF treatment who declined to implant an embryo due to the PGT-A test but later switched specialists and clinics and went ahead — successfully, years later. As she told the newspaper about her healthy son:

“I was 39 when I made his embryo. 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.”

U.S. warns about prenatal blood tests

The federal Food and Drug Administration, meantime, has offered a sharp caution for expectant couples who have experimented with prenatal blood tests to screen fetuses for rare genetic conditions, the New York Times reported, separately. The newspaper quoted a statement from Dr. Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health:

“While genetic noninvasive prenatal screening tests are widely used today, these tests have not been reviewed by the FDA and may be making claims about their performance and use that are not based on sound science.”

The New York Times independently investigated the blood tests with expert assistance recently, reporting:

“[A] New York Times examination in January … reported on the incidence of false positive results in some of these tests, known as noninvasive prenatal screening tests, or NIPTs. That article quoted women who received false positive screening results for extremely rare conditions; highlighted examples of misleading marketing by companies selling the tests; and described some reports of pregnancies that were terminated based on a screening without a confirmatory test. The agency warned doctors not to diagnose genetic disorders based on these results alone and stressed the need to follow positive screenings with more reliable ‘diagnostic’ testing. It said it was ‘aware of reports’ that some women ‘have ended pregnancies based only on the results’ of these genetic screening tests.”

The newspaper had further information about the burgeoning use of these blood tests:

“The tests are taken by over a third of pregnant women in the United States. But they fall into a category called lab-developed tests, which are not regulated or approved by the FDA. In its safety notice, the agency said it was working with Congress ‘on legislation to establish a modern regulatory framework for all tests,’ including the category that covers these screenings. The agency’s warning comes after numerous accounts, dating back years, of misinterpretations of the screenings as being definitive. But the criticism has intensified in recent months, with 97 Republican legislators sending a letter to the FDA in January, prompted by the Times article. ‘This is an area that has concerned the agency for a long time,’ said Alberto Gutierrez, the former director of the FDA office that oversees many medical test The lack of regulation of lab-developed tests ‘has led to many cases where the laboratories have claimed more than they should based on the data that is available,’ he added. The warning does not come with any consequence for prenatal test manufacturers. But it urged them to submit their products for voluntary approval. A spokeswoman for the agency declined to say whether it was currently working with any manufacturers on this front.”

In my practice, I see not only the harms that patients suffer while seeking medical services, but also the damage that can be inflicted on them and their loved ones by defensive and excessive over testing, over diagnosis, misdiagnosis, and over-treatment. Patients struggle too much already to afford needed medical services much less those that are invasive, painful, wasteful, and unnecessary.

Up to a third of medical spending goes for over-treatment and over-testing, with an estimated $200 billion in the U.S. expended on medical services with little benefit to patients. But getting doctors and hospitals to stop this excess isn’t easy, nor is it a snap to get patients to understand what this problem’s all about so they’ll push their health care providers to do something about it.

With medical tests, like the dubious rare-disease prenatal blood screen promoted by Silicon Valley firms, serious questions must be asked about the dearth of federal oversight. It has been opposed by those who argue that patients benefit best by government staying out of the way of innovation

Caveat emptor, consumers. Patients must insist that their doctors explain fully any test or procedure. This is patients’ fundamental right to informed consent. This means they are told clearly and fully all the important facts they need to make an intelligent decision about what treatments to have, where to get them, and from whom. Patients, in turn, must put in the effort to safeguard themselves by improving their knowledge and comprehension about their care — a constant learning process that is crucial for those who wish to bring new lives into the world and to nurture them for decades after.

We have much work to do to rein in costly, wasteful, and harmful testing.

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
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