PGT, PGS, PGD, chromosomal abnormalities…if you’re undergoing IVF and considering genetic testing, you’ll probably hear these terms getting thrown around a lot. So, unless you have a fertility dictionary on hand at all times, you might be left wondering—what the heck does it all mean? Here’s what you need to know.
What is PGS testing, anyway?
First things first. PGS (“Preimplantation Genetic Screening”) and PGD (“Preimplantation Genetic Diagnosis”…more on that later!) both fall into the category of PGT (“Preimplantation Genetic Testing”). They each provide a way to test an embryo for genetic abnormalities prior to transferring it in hopes of it growing into a healthy baby. Sounds pretty self-explanatory, but since we’ve been through this infertility rodeo, we know there’s nothing about this process that isn’t complicated.
What PGS testing means
These days, PGS is actually called PGT-A, or “Preimplantation Genetic Testing for Aneuploidies,” but for the sake of this article, we’ll continue to refer to it as PGS. PGS testing looks at an embryo to see if it contains the correct amount of chromosomes. Embryos with the right number of chromosomes — 46 — are considered “euploid,” and those with extra chromosomes or chromosome deletions are considered “aneuploid.”
Different doctors have different philosophies on PGS testing. But there are a few reasons Dr. Knopman cites that PGS can be beneficial:
- It can increase pregnancy rates: While an embryo might look awesome to an embryologist, morphology might not tell the whole story. According to Dr. Knopman, doing PGS may help you avoid moving forward with a transfer that might not yield you anything positive—especially in women between the ages of 38-41.
- It can reduce the risk of miscarriage: If you do get pregnant, some data shows that you’re less likely to miscarry with a PGS tested embryo. If you’re a numbers gal, consider this: a Fertility and Sterility review indicated a decrease in miscarriage rates from 28% in the natural conception group to 9% in the group using a PGS embryo. This mostly applies if you fall into any of the categories outlined below (see “Who should do PGS testing?”).
- It can explain previously “unexplained” infertility: Sometimes, PGS can solve the conundrum of why you aren’t getting pregnant. It’s possible that you and your partner have been creating abnormal embryos, and PGS can clarify that.
Who should do PGS testing?
If you’re undergoing IVF and fall into any of these categories, it might be worth chatting with your doctor about PGS testing to see if it’s right for you if you:
- You’ve faced recurrent pregnancy loss: if you’ve suffered multiple losses, there could be a chromosomal abnormality at play that prevented those embryos from developing. PGS may give a glimpse at what’s going on and (hopefully) yield at least one “genetically normal” embryo that some doctors believe will give you the best shot at a successful transfer.
- You’re over 35: if you’re in this age bucket, you may not want to spend the time waiting to see if other embryos “take” (hey, who does?) and risk deteriorating egg quality over time.
- You have a lot of blastocyst-stage embryos: if you have many embryos that have made it to blastocyst stage (developing steadily for 5-7 days) — first of all, that’s awesome. Hopefully your good luck continues! But if you can swing it, it might be worth conducting PGS testing to see which of the bunch may give you an extra boost of confidence pre-transfer.
How does PGS testing work? How long does it take?
In summary, the PGS testing process looks a little somethin’ like this:
- Day 1: Eggs retrieved and (hopefully) fertilized
- Days 2-5: Fertilized embryos continue to grow to blastocyst stage
- Days 5-7: Blastocyst embryos are biopsied with the material sent to be analyzed for chromosomal abnormalities.
- Days 14-28: PGS testing results return, telling you a yay/nay if the embryos are “chromosomally normal.”
PGS testing requires an embryo that has already grown to blastocyst stage, which usually isn’t until 5-7 days after the egg has been fertilized. A biopsy is taken from the blastocyst embryo, specifically of the trophectoderm cells (that ultimately end up becoming placenta) — not of the inner cells that eventually form a baby — and analyzed to understand the chromosomal makeup of that cell. The full PGS testing analysis usually takes 1-2 weeks.
How much does PGS testing cost?
As with all IVF costs, the cost of PGS testing totally varies by clinic. Some clinics charge a flat rate for PGS testing, no matter how many embryos they’re looking at. Other clinics charge per embryo or with tiers. So PGS testing for 4-6 embryos might cost one amount while testing 7-10 embryos might cost another amount.
Before beginning your IVF cycle, ask your clinic upfront how they bill these costs. Unfortunately, PGS isn’t always covered by insurance. Plans are beginning to cover it more, but your clinic must deem it medically necessary.
If you’re paying out of pocket for PGS testing, it can run in the thousands — we’ve seen up to $3,000 for testing 11-14 embryos. If your clinic charges by tier and you know you will end up doing more than one round of IVF, it may be worth waiting (read: cheaper) until you’ve completed all retrieval cycles so you can pool your embryos together and test them in bulk.
Are there any risks of PGS testing?
During PGS testing, it’s largely believed that biopsying trophectoderm cells from a blastocyst embryo is safe and won’t harm the embryo. But, back in the day when embryos were only grown for 3 days (to “cleavage stage”) and not to blastocyst, there were far fewer cells (and no trophectoderm cells) to work with. So biopsying a few of them made more of a difference, resulting in a 39% decrease in implantation rates. Insert *head explosion emoji* here.
That being said, there is still some debate about whether or not PGS testing still affects the health of an embryo. One factor that may affect this is the amount of cells taken during the embryo biopsy. The more cells that are taken could lead to that embryo having a harder time developing afterwards. It’s also preferred to use a more developed embryo, or a blastocyst that’s already “hatched.” By and large, though, with today’s technology, PGS is considered safe, A 2018 Fertility and Sterility article specifically notes that, “To the best of current knowledge, embryo biopsy is not linked to fetal malformations or other identifiable problems in offspring.”
One thing to consider, though we hate to say it, is that a PGS normal embryo is not a sure bet for a successful pregnancy or even implantation. While it could feel like the holy grail, nothing on a fertility journey is ever guaranteed, unfortunately. We suggest talking to your doctor about what makes the most sense for you and those embabies of yours.
I’ve also heard about PGD testing. What’s that?
Sure, PGD is just one letter off from PGS. But swapping out that “S” for a “D” actually makes a big difference in what’s being looked at.
PGS vs. PGD testing: the showdown
While PGS testing examines the number of chromosomes in a biopsied cell, PGD looks for the existence of specific inherited genetic abnormalities or chromosome rearrangements. PGD testing falls into two categories:
- Preimplantation Genetic Testing for Monogenic/Single-Gene Disorders (PGT-M): Looks for specific genetic abnormalities controlled by a single gene, like Fragile X syndrome or the BRCA mutation.
- Preimplantation Genetic Testing for Chromosomal Structural Rearrangements (PGT-SR): Examining specific inherited chromosomal abnormalities, like reciprocal translocations.
In short, PGS testing gives you a bird’s eye view of which embryos might be genetically abnormal, while PGD gives you a more detailed picture — but you’d need to know what, specifically, you’re looking for. Which brings us to…
Who should do PGD testing?
Although it would require undergoing IVF, if you fall into any of the below categories, conducting PGD testing could help you get closer to having a baby that is not a carrier of that particular genetic condition or chromosomal abnormality you’re trying to screen for.
If any of these apply to you and your partner, it might be worth chatting with your doctor about PGD (PGT-M) testing:
- You are a carrier of an X-linked condition
- You and your partner both carry the same autosomal recessive condition (like Cystic Fibrosis)
- You or your partner have an autosomal dominant condition
- You or your partner have a mutation associated with a hereditary cancer
- You already had a pregnancy (or child) with a single gene disorder
How much does PGD testing cost?
If you’re undergoing PGD testing, you’ve probably been through the fertility ringer, so we’re here to tell you some good news — PGD is often covered under most insurance plans as long as the patient and partner are carriers for the same disease.
Out of pocket, PGD can cost anywhere between $4,000 – $10,000, depending on the cost of creating a specific probe needed to check for the presence of that particular gene. If you’re seeking to check for more than one gene, that would involve building a separate probe and an additional cost.
Some stuff to think about re: PGS and PGD testing
Genetic testing isn’t for the faint of heart…or wallet. So here are a few commonly-asked considerations to take into account before taking the plunge.
Should I do PGS testing on previously frozen embryos?
In short, it depends. While it’s definitely possible to thaw embryos, biopsy, and re-freeze, there are, unfortunately, always potential embryo survival implications whenever you thaw. Just something to keep in mind as you manage your own expectations.
If you’re thinking about thawing your embryos to conduct PGS testing, Dr. Jaime Knopman, reproductive endocrinologist at CCRM NY, advises to consider how many embryos you have, in addition to your age and if/how many times you have had previous failed transfers. “It’s definitely a conversation to have with your physician,” she says.
It also matters what type of embryos you’re thawing. A 2011 study published in the Journal of Human Reproductive Sciences, for instance, states that thaw survival rate improves when the embryo has reached blastocyst stage (versus, say, a day-3 embryo or zygote). And, according to Dr. Knopman, the same goes for the actual process of PGS: the more advanced the embryo is, the fewer risks you’ll encounter—biopsying a couple of cells of a day-5 embryo gives more to work with than one cell of a day-3 embryo—and the more accurate the results may be.
Some good news to think about: according to the Ethics Committee of the American Society of Reproductive Medicine, as we’ve mentioned, current research does not indicate any risks of birth defects associated with biopsied normal embryos vs. embryos that haven’t undergone PGS. In other words, conducting PGS on an embryo shouldn’t contribute to any additional risks beyond the existing risks of IVF.
What about mosaic embryos?
You may have heard the term “mosaic embryo” and wonder what the heck that is. A mosaic embryo is an embryo that, during PGS testing, is found to contain both normal and abnormal cells.
In the past, any found abnormalities would render the embryos useless for transfer and doctors would recommend discarding them no matter what. However, today, some doctors believe that transferring mosaic embryos can still lead to success — with any abnormal cells likely going to non-essential pregnancy tissue that don’t contribute to the baby’s chromosomal development.
If gender is especially important (say, if the only girl embryo you have is mosaic), or if your IVF cycle did not yield as many embryos as you’d like to have, find out if any of your embryos are considered mosaic and chat with your doctor about the best course of action.
What should I do with “abnormal” embryos?
What you might do with any abnormal embryos is obviously a very personal choice (and a tough one, we’ve been there), but in some cases, your clinic may have policies in place that may dictate next steps.
Data shows that transferring an abnormal embryo increases the risk of miscarriage, diseases or birth defects. Because of this, most clinics will refuse to move forward with a transfer of such embryos and some will even require you to discard them. Other clinics may take the opposite approach, hanging on to all embryos until you are 150% certain that you are done having children. Either way, when you have abnormal embryos, your options include:
- Discard them: Any abnormal embryos will be destroyed and not available for use in the future.
- Save them: Keep them in the freezer until you either (a) decide to destroy them at a later date after thinking it through, or (b) decide to use them (if your doctor and clinic allows this) after taking all risks into account.
- Donate them for research: If you aren’t planning on using any abnormal embryos, donating them for research could help embryologists, REs, and future #ttcwarriors learn a ton down the line.
You are typically required to determine your choice of what you’d hypothetically do with any abnormal embryos prior to retrieval and transfer. That being said, we’re all humans who sometimes change our minds. Before moving forward with any actions taken on abnormal embryos, make sure you’ve given it a lot of thought and, if necessary, discussed it at length with your partner and doctor.
Summing it up
As if IVF wasn’t already overwhelming enough, throw PGS and PGD testing into the mix and your head might be spinning. If this sounds like you, we get it. Set up a dedicated time to chat with your doctor (or, better yet, an embryologist at your clinic’s lab) to get clear on your options.
We know the path to parenthood isn’t always easy, but we’re here to make sure you know that this tough decision-making can be so worth it. Good luck!