What an Embryologist Really Thinks About PGT-A, ICSI, and More
By Carol Curchoe, PhD
I am a clinical embryologist, a position that has held the highest place of honor among the many accomplishments I have achieved throughout my career. I also know first-hand the pain, emptiness, and emotional anguish that comes from not being able to build the family you desperately want when you want it.
As the person behind-the-scenes in the IVF lab, I can’t describe the profound happiness that comes from being there at the very beginning of your family. From literally choosing the genes that will become your living child and placing those resulting embryos into your uterus to performing microsurgery with fancy robotics and replicating the site of human fertilization (i.e. the fallopian tube) in the lab. We make miracles happen, it's true.
I have seen pregnancies from just one egg retrieved, from azoospermia cases where nearly no sperm can be found, and from poorly-graded embryos that visually look like they don’t have a chance, but somehow make it. I have also seen the devastating consequences when things don’t go as expected: a human error is made, something goes wrong because of one minor loss of concentration, or things happen beyond our control such as a stimulation cycle that yields no eggs, eggs that don’t fertilize, or eggs that do fertilize but then arrest by day 3 or disintegrate by day 5. Sometimes we don’t have answers, and that’s painful, too.
One of the things I’m often asked about, besides what life in the lab is like, are the more controversial questions. They always start off like this: “What do you, as an embryologist, think about…XYZ.” So today, I want to share my opinions on the two topics I get asked about the most, with the disclaimer that this isn’t medical advice, and you should always consult with your fertility specialist before making any decisions.
Does PGT-A testing work?
Pre-implantation Testing for Aneuploidy (PGT-A) is a hotly debated topic in the world of IVF. As an embryologist, I am personally conflicted about using this test for every patient. All too often, IVF cycles with PGT-A return the devastating result: morphologically gorgeous embryos are deemed abnormal by PGT-A and therefore “not suitable for transfer.”
There is no doubt in my mind that for a person who has a lot of embryos, ranking them in quality order is highly effective in reducing the number of embryo transfers needed to get a “big fat positive” and possibly even reducing the rate of miscarriage. However, I also believe that PGT-A is overused, especially for embryos with oocyte sources between the ages of 20-35.
Why? Because embryo biopsy damages the embryo, even if just a little bit. We are, after all, plucking 5-10 cells off the embryo. While we do that, we are holding and stretching the embryo and its cells. We are keeping it out of the incubator and excessively manipulating it, shooting it with a laser or “flicking’ it to break the cells free.
You also have all levels of skilled practitioners performing this microsurgical trophectoderm biopsy technique, from newly trained to senior embryologists, and we now know that differences between embryologist skill levels can be detected in PGT results. In just one example, rates of “mosaic” results between embryologists in data recently presented by a popular genetics testing lab backs this up. However, much more research is needed on this topic.
So now, let’s get to where my real internal conflict with using this technique lies. We know from several types of research that there is a certain “false” positive result rate related to PGT-A testing. In other words, the genetic testing result and the embryo's “viability,” or the ability of the embryo to turn into a healthy pregnancy, do not completely overlap. We also know that many genetic testing companies or fertility clinics choose to call “mosaic” embryos and “segmental aneuploid” embryos “abnormal” and discard them or refuse to transfer them. These embryos have a proven clinical pregnancy rate that hovers somewhere in the 25%-30% range, while the rate of “false” results is purportedly much lower, around 2%. So, what if a patient’s IVF cycle returns only abnormal embryos? What if they only have one “abnormal” embryo to work with? Are we really helping patients by saying they cannot try with that embryo?
No one can say for certain that an embryo doesn’t have a slight chance. And yet, most physicians will not transfer embryos that have been designated as abnormal, and many will not transfer mosaic embryos, either. I fall on the side of giving every embryo a chance, if (and only if) the patient has been properly counseled and understands the risks: that only one or two embryos out of every 100 that are truly abnormal (not mosaic or segmental) can result in a healthy pregnancy.
Should ICSI be used for every IVF patient?
ICSI stands for intracytoplasmic sperm injection. ICSI is a microsurgical procedure using fancy robotics during which an embryologist takes a single sperm cell and injects it into an egg with a needle finer than a human baby hair. ICSI was developed in the ’90s specifically to treat male factor infertility, but it has quickly gained prominence and is now used almost exclusively by IVF clinics in the U.S. as the standard of care.
From an embryologist’s point of view, ICSI is an extremely effective technique that all-but-ensures fertilization will occur. Before we started using ICSI, failed fertilization was a lot more common in IVF labs. Performing ICSI allows us to inspect the eggs, providing critical information to the REI about the quality of the stimulation and maturity of the oocytes at the time of the retrieval. When I perform ICSI, I can also inspect each sperm cell and choose to inject only the best-looking ones (sperm morphology has been positively correlated with embryo development).
Using ICSI for every IVF patient has been critiqued, as this skill takes many years to master, and again, there is likely a large difference in fertilization rates, “usable blastocyst rates,” and perhaps even “normal” blastocyst rates between ICSI technologists. Some say it is unnatural manipulation of the egg and sperm and adds additional costs to each IVF cycle. But for me, IVF already leaves so much “up to chance,” and I want to do everything in my power to ensure that your IVF cycle results in a healthy baby! ICSI helps us get closer to that goal.
Why don’t we have concrete answers to these IVF questions?
Aside from “Does PGT-A work?” or “Should we use ICSI for every patient?,” there are so many questions that are still left unanswered when it comes to IVF, with so much conflicting research. Do you need an ERA test? Does EmbryoGlue work? Should time-lapse incubators be used? What culture media is the best? Should the lights be on or off in an IVF Lab? Should embryos be cultured together or separately? Should the eggs be stripped right after the retrieval and injected immediately or is there an optimal timing? Why is early miscarriage so common? Why are abnormal embryos SO common? Should the embryo media be changed often or not at all? What about IVF “add-ons”?
Unfortunately, not only are “women’s issues” underfunded in medical research, but women, particularly those trying to conceive or pregnant, have been systematically and purposefully excluded from clinical trials for various reasons. More surprisingly, since 1996 there has been no federal funding allowed for human embryo-related research. The Dickey-Wicker Amendment specifically prohibits federal funding for any research that creates or could destroy a human embryo in the process of that research.
Remember, the science of IVF is only 40 years old. The first baby born from IVF in the U.S., Elizabeth Carr, is actually younger than I am. That means that for almost the entire existence of this field, there has been no funding for some of these truly important questions in embryology. Therefore, much of the existing research is performed on animal models like mice, sheep, or cattle that don’t exactly compare to human embryos. In addition, much of the support for this type of research is provided by commercial companies that hope to benefit financially from the outcome of the studies.
Infertility affects 1 in 8 couples in the U.S., and that is probably an underestimate. Almost everyone I know has somehow been impacted negatively by infertility or pregnancy loss. In my opinion, the best American scientists should be turned loose on these research questions and given all the funding they need to find concrete answers. After all, the future of our population is at stake.
Carol Curchoe, PhD is a Clinical Embryologist and Founder of ART Compass.