How reliable is non-invasive embryo genetic testing?

When scientists and doctors help families have babies using in vitro fertilization (IVF), they want to make sure the embryos are healthy. One important step is checking if an embryo has the right number of chromosomes, which are packages of DNA in our cells. If an embryo has the wrong number of chromosomes (called "aneuploidy"), it may not grow well or could lead to miscarriage. That’s where preimplantation genetic testing for aneuploidy (PGT-A) comes in. Traditionally, this testing involves taking a few cells from the outer layer of an embryo, called a trophectoderm (TE) biopsy. But this method is invasive because it means poking the embryo to remove cells, which sounds a bit scary to many people.

More recently, scientists have been exploring a gentler, non-invasive way to test embryos: non-invasive PGT-A (niPGT-A). Instead of taking cells from the embryo, niPGT-A looks for tiny bits of DNA (called cell-free DNA or cfDNA) that embryos release into the liquid they are grown in. Researchers hoped this would give the same information about chromosomes, but without touching the embryo at all. Sounds perfect, right? But how well does it actually work in practice?

What is non-invasive PGT-A and how does it work?

Non-invasive PGT-A (niPGT-A) is like being a detective who solves a mystery without disturbing any evidence. In IVF labs, embryos are grown in special drops of liquid, called spent culture medium (SCM). As embryos develop, they shed bits of cfDNA into this liquid. Scientists collect the liquid and use advanced DNA sequencing to look for chromosome problems, aiming to tell if an embryo is healthy without ever touching it. This approach avoids the risks that may come with a TE biopsy, such as damaging the embryo or stressing it out.

However, the big question is whether these tiny DNA fragments in the liquid truly represent the embryo’s real chromosome makeup. Sometimes, the cfDNA can be mixed with DNA from the mother or even other cells, making it hard to be sure where the DNA is coming from. Researchers have been working hard to figure out if niPGT-A can be trusted for important decisions, like choosing which embryo to transfer.

Comparing niPGT-A to traditional biopsy methods

A recent study published in Scientific Reports took a close look at this question by testing 212 embryos from 98 couples with both niPGT-A and the traditional TE biopsy method. All embryos were checked using both methods, but doctors only used the TE biopsy results when deciding which embryos to transfer. The scientists wanted to see if niPGT-A was as accurate as the older, more invasive method.

They found that the non-invasive method worked better if the embryos were grown for an extra day, which allowed more cfDNA to appear in the liquid. With this longer culture, the informative rate for niPGT-A jumped from about 69% to 98%. However, while niPGT-A was very good at spotting embryos with chromosome problems (over 91% sensitivity), it wasn’t as good at confirming which embryos were truly healthy (only about 51% specificity). This means niPGT-A often labeled healthy embryos as unhealthy by mistake—a problem called false positives. You can read more about how scientists measure the accuracy of health technologies, including health AI and genetic tests, in this helpful SlothMD article: how we measure if AI health checkers are accurate.

Why does accuracy matter so much?

Imagine being told your favorite toy is broken, but it turns out it works just fine. In IVF, a false positive means a healthy embryo could be thrown away for no reason, which is heartbreaking for families. The study found that many embryos called “abnormal” by niPGT-A were actually healthy according to the TE biopsy and led to successful pregnancies and healthy babies. In fact, embryos with these "discordant" results (healthy by TE biopsy, unhealthy by niPGT-A) had a pregnancy rate of 94% and a live birth rate of 88% after transfer. This shows that niPGT-A, in its current form, isn’t reliable enough to be used alone when choosing embryos.

Other studies agree. For example, a review published in the journal Current Opinion in Obstetrics & Gynecology highlights that while non-invasive testing is a promising idea, it still faces big challenges with accuracy and contamination risk (noninvasive preimplantation genetic testing using the embryo spent culture medium).

The technical and biological hurdles

So, why does niPGT-A have trouble getting it right? The main issues are:

• The cfDNA in the culture medium is a mix of DNA from different sources, not just the embryo.

• Sometimes, the DNA is too broken up or there isn’t enough of it to give a clear answer.

• Each embryo is different, so some release more DNA than others.

Research teams have suggested ways to improve things, like growing embryos a bit longer to get more DNA, or using better lab techniques to reduce contamination (optimizing non-invasive preimplantation genetic testing). But even with these tweaks, niPGT-A can still misclassify embryos.

What it means for patients and the future of IVF

For now, traditional TE biopsy remains the most reliable way to check embryo chromosomes in IVF. Non-invasive testing is not yet accurate enough for doctors to choose which embryos to transfer. It’s important for hopeful parents to know this, so they don’t accidentally miss out on a chance at pregnancy due to a false positive. As technology and health AI tools improve, these tests may get better, but for now, caution is needed.

If you want to learn more about how scientific studies are shaping the future of health AI—including in fertility care—check out this SlothMD article: ChatGPT medical accuracy 2024.

The journey to safer, more accurate, and less invasive embryo testing continues. Teams around the world are working on improving the science, so one day non-invasive testing might truly make IVF easier and safer for everyone. Until then, careful research and honest conversations between doctors and patients are key to making the best choices in fertility care.