An IVF Embryo Test Aims to Prevent Miscarriages: Is It Worth It?

An IVF Embryo Test Aims to Prevent Miscarriages: Is It Worth It? thumbnail

Fertility patients who have undergone in vitro fertilization (IVF), are advised to purchase a costly supplemental test called preimplantation gene testing for aneuploidy (PGT–A). This involves removing a few cells from the embryo to check their DNA. PGT-A is a popular option for those who have the means to pay. It can detect genetic abnormalities that could increase the likelihood of a miscarriage if it occurs.

The widespread use of the test has also caused controversy. The authors of an April 2022 study in Human Reproduction have sparked debate and alarmed prospective parents by suggesting that many clinics are too quick to discard embryos based on PGT-A and are ignoring a growing body of evidence that some of these embryos are capable of producing a viable pregnancy.

If all embryos from a patient are rejected based upon PGT-A results they may lose their only chance of taking home a baby. Or they could be directed to expensive alternative technologies like donor eggs, which would deprive them a child genetically related with both parents. In a quote in a 2017 article in New York Magazine‘s the Cut, study co-author Norbert Gleicher of the Center for Human Reproduction in New York City called this waste of potentially good embryos “an unprecedented scandal.”

Proponents have strongly reacted to this criticism. They claim that PGT-A is a cost-effective option for patients and allows them to make informed decisions about the viability of each embryo. PGT-A is also believed to have reduced the risks and costs of IVF in its earlier iterations.

The delicate process of combining paternal and maternal chromosomes in a halving operation is often a risky one. This can lead to embryos with extra or missing DNA, which can cause a pregnancy to be canceled or delayed. Aneuploidy is the leading cause of miscarriage during the first trimester. This is why many couples who hope to implant one egg per cycle are not able to have children. Artificial hormonal stimulation is used to induce multiple eggs to ripen in IVF. These eggs are then removed and fertilized in a lab to produce as many embryos possible. PGT-A was created to give doctors a better basis in embryo selection than just looking at them under a microscope. This is a highly subjective form of assessment that relies heavily on gut instinct and eyeballs.

For patients with a lot of embryos, the benefits of PGT-A are obvious. The number of IVF cycles necessary to achieve a successful pregnancy can be reduced by removing the embryos most likely for miscarriage. Each IVF cycle is costly and, like miscarriage and other complications, emotionally and physically taxing. According to Teresa Cacchione (reproductive medicine associates of New York), the use of PGT–A has allowed a recent shift in practice, where one embryo is transferred into the uterus per cycle, rather than two or three. This has drastically reduced the number of IVF-conceived babies who are twins, triplets or higher-order multiples.

While the logic behind PGT-A seems sound, embryo biopsy has been exposed as a problem. David Barad, Center for Human Reproduction’s lead author, points out that the cells biopsied only a small portion of the whole. They are taken from the tissue that will eventually become the placenta, not the fetus. He says, “If you reach down into a field of wildflowers, close your eyes, and pull up three flowers, it doesn’t mean that the field is all-blue.” Other studies have also shown that PGTA does a good job of representing the mix cells in an embryo.

Testing has shown that many embryos, and perhaps even all embryos, are actually a mixture of different cell lines with different DNA complements. As cells divide and multiply, mistakes can occur. These mistakes are usually fatal, but the surviving cells will be able to pass on any changes made to their daughter cells, creating an alternative genetic lineage. This is called mosaicism. A 2020 American Society for Reproductive Medicine (ASRM) paper estimated that the odds of reproductive success are inversely related to the level of mosaicism identified in an embryo.

In practice, embryos are classified as fully aneuploid rather than mosaic when more than 80 percent of the cells biopsied show one or more genetic abnormalities. Cacchione states that her facility won’t transfer embryos with genetic abnormalities at this stage “because there is a very low chance of an ongoing pregnancy and a high risk of loss.” However, Reproductive Medicine Associates in New York will offer parents the option to transfer embryos that have been identified as mosaic. Some clinics won’t, despite advice from ASRM that this is possible with appropriate counseling.

In their study, Barad & his co-authors transferred both fully aneuploid and mosaic embryos after patients were denied access to them at other clinics. These results, which are consistent with previous research, show that mosaic embryos can often produce a successful pregnancy. It is interesting to note that the rogue cells with missing or added DNA often disappear completely in follow-up testing of a child or fetus.

Some have been surprised by this embryo’s resilience. Experts believe that embryos can self-correct when healthy cells outperform the competition, pushing aneuploid cells into obsolescence. Jamie Grifo, director at the NYU Langone Fertility Center says, “It didn’t surprise me at any,” because we knew from previous experience that any embryo can have a shot.” But long shots come with high costs. Grifo posits that it might take more than 125 transfers of fully aneuploid embryos to get a single pregnancy; all of those other transfers represent failed cycles of IVF, including an estimated 35 to 40 miscarriages. Though Barad champions the use of both mosaic and fully aneuploid embryos, the differences between the two in his own data were stark: 23 mosaic embryos transferred produced six live births, while 79 fully aneuploid embryos produced only two.

The fear that aneuploid embryos or mosaic embryos could give rise to serious medical problems is lurking in the background. Cacchione admits to the concern with patients. She says that she doesn’t have any long-term data. “Most of the children born from known mosaic transfers are younger than four years old,” she says. But, she also points out that doctors unwittingly transferred mosaic embryos for decades before routine use of PGT–A. There is no evidence of an increase in birth defects. Cacchione states, “That’s all very reassuring.” Barad says that concerns about malpractice could limit clinics’ willingness for patients to try embryos deemed abnormal. “Some institutions are being governed by their lawyers,” he said.

Barad claims that aggressive marketing of PGT-A, which typically adds $4,000 to $5,000 to the cost of IVF, may be resulting in overuse. Cacchione claims the test is useful for anyone who can afford it, as long as it is combined with good counseling. PGT-A allows patients and their families to weigh the likelihood of a successful pregnancy against the costs of IVF and the emotional and physical toll of miscarriage. In the end, Cacchione says, “it’s a very personal decision.”

ABOUT THE AUTHOR(S)

    Laura Hercher is a genetic counselor and director of student research at the Joan H. Marks Graduate Program in Human Genetics at Sarah Lawrence College. Hercher has published extensively on ethical, legal, and social issues in genetic medicine. Hercher is

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