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Deborah Howell (Host): Genetic testing sounds pretty futuristic and maybe a little intimidating, but it's proven itself to be an effective tool in the area of fertility treatment. Today, we're going to find out all about pre-implantation genetic testing with an expert in the field. I'm Deborah Howell and our guest today is Dr. Juan Alvarez, a Reproductive Endocrinologist at Fertility Centers of Illinois.

This is The Time to Talk Fertility Podcast. I'm your host, Deborah Howell. Dr. Alvarez, before we jump into pre-implantation genetic testing, can you give us some of the basic info that we should know?

Juan Alvarez, MD (Guest): Yes. So, some of the basic information includes what is pre-implantation genetic testing, right? Basically what we do is a biopsy on embryos to be able to look at the copy number of chromosomes and we all have 46 chromosomes. And therefore that is what the test is looking for.

Host: And then what is aneuploidy?

Dr. Alvarez: So, aneuploidy is the term for incorrect number of chromosomes. It could either be missing chromosomes or extra chromosomes. Like I said before, we will have 46 chromosomes. So, aneuploidy would be an embryo or anyone who has these missing or extra chromosomes.

Host: Got it. And what are the causes of chromosome abnormalities?

Dr. Alvarez: The causes of chromosome abnormalities is due to the quality of the egg. And this happens when the egg and the sperm fertilize and with the first cell division, the egg has to power the division of the chromosomes. So it could be even and normal. And when this doesn't happen when there's an unevenness of division between the cells, you get abnormal copy numbers of the chromosomes.

Host: And how common is a chromosomal abnormality.

Dr. Alvarez: It is age dependent female age dependent on how common chromosome abnormalities are. For women who are less than 35 years of age, it's usually around 30% of embryos that are aneuploid. A woman who's 40 years of age, greater than 50%. And then for women who are greater than 42, it's about 80%abnormal chromosomes.

Host: That's significant. Now, can you that's a simple definition for pre-implantation genetic testing?

Dr. Alvarez: Pre-implantation genetic testing is a tool that we use in IVF. After we have embryos, we do a biopsy. We send those cells that we biopsy to do genetic analysis in order to know the copy number of the embryo.

Host: And how many different types of PGT are there?

Dr. Alvarez: There are three different types of PGT. The most common PGT is for aneuploidy or it's called PGT-A. So this is the one that we've been talking about, the test that looks for copy number of chromosomes. Now there's two other ones. One is called PGT-M or for monosomy disorders and PGT-SR or structural rearrangements.

For the PGT-M we're looking for a specific genetic disorder that the parents might have, the most common one being cystic fibrosis. So, that's a single gene disorder that we're looking for. For PGT-SR, which is a structural rearrangement, we're looking to see if there's any overall structural abnormalities in the chromosomes. More specifically, we're looking to see if there's anything like a translocation, where one piece of one chromosome is stuck to another piece of a chromosome. That would be global structural rearrangement that could cause miscarriages. So, that's the third type and those two types are less common. And the most common one is PGT-A.

Host: And what types of infertility diagnoses warrant PGT?

Dr. Alvarez: There are several indications for PGT. One of them would be advanced maternal age. We do know through various studies that doing PGT is worthwhile or it has a positive effect on women who are greater than 35. Now because of IVF couples have the ability to do PGT, even if they don't have a clear medical indication for it.

Host: And what types of chromosomal abnormalities are screened for with PGT?

Dr. Alvarez: Well, like I said before the most common abnormality is an error in copy number of chromosomes. The reason for that is because as humans, we all have 46 copies of our chromosomes, 23 pairs, one pair from mom, one pair from dad. And therefore that is the only way that we are normal.

And so PGT really tells us if an embryo is viable to become a pregnancy, because if an embryo is genetically abnormal, it either would not lead to a pregnancy; so you would do the transfer and there was no pregnancy, or if it's one of the abnormalities that could lead to a pregnancy, it could lead to either miscarriage or another genetic abnormality like trisomy 21, which causes Down's Syndrome.

Host: And doctor, how do you decide which type of PGT to recommend?

Dr. Alvarez: This is all due to female age and any other genetic factors. When patients see us in the clinic, we go through a full genetic history. And we also screen for recessive genetic disorders. If the couple has any recessive disorders, then we would be doing PGT-M for monosomy. If a couple is, just doing PGT to increase their odds of getting pregnant, we would do PGT-A, looking for aneuploidy, we're screening the embryos that are going to lead to a pregnancy. So that's how I decide.

Host: And I'm curious, what does the latest medical research say about PGT?

Dr. Alvarez: Well, first of all, we know that it's safe. We've done various studies to look at the impact of embryo biopsy. Research is also showing that for younger patients, less than 35doing PGT is not advantageous in the sense of pregnancy rates. It doesn't increase the odds of getting pregnant because the majority of your embryos are going to be screened are going to be genetically normal. So, we are really using this test to weed out the embryos that would not lead to a pregnancy. And the majority of embryos for women who are less than 35 will be genetically normal. We also know through the literature that doing single embryo transfers is the best way to do embryo transfers in patients who've done PGT because transferring two embryos, doesn't significantly increase the odds of getting pregnant. And then the latest research has shown that the biggest benefit is for women who are older than 38.

Host: All right now, do some patients do PGT without any diagnosed medical need? And if so, why would they do that?

Dr. Alvarez: Yes, many patients do. For several reasons, one could be for sex selection. So when we do PGT, not only do we get the copy number of chromosomes, we also get sex chromosomes. So, usually the readout for a PGT results would be something like46 XX, or female embryo or 46 XY, male embryo. So for sex selection Some patients have had many miscarriages or recurrent miscarriages. And so a way to avoid another miscarriage would be to do PGT. So, these are different modalities that PGT is used other than forage factor.

Host: Of course, the burning question a lot of people want to know is, does PGT create so-called designer babies?

Dr. Alvarez: Right. And that's one of the biggest questions that I get and no, we do not make any designer babies. The term designer baby implies that we're able to manipulate or change something about the embryo, but what we really doing with PGT, we're only analyzing the embryo. So, when we take the biopsy and we analyze the cells, we get a read out of the chromosome makeup of the embryo. We are very far away from being able to go back and be able to edit the genome of the embryo to be able to design a baby or change the genetic makeup of an embryo.

Host: Good to now. What's the process of PGT?

Dr. Alvarez: So the process involves doing IVF. So, we would stimulate the female patient to be able to extract her eggs. We fertilize the eggs in the laboratory with the partner's sperm, and then we grow out the embryos in the laboratory for five days. After the fifth day of development, the embryo has made it to what's called the blastocyst stage.

In this stage, there's two cell lines. There's going to be the inner cell mass. That's going to become the baby. And then on the outside is the trophectoderm cell layer and that's what's going to become the placenta. So, that is what we're going to be biopsying on day five. So on day five, the cells get biopsied. The embryo gets frozen, the cells get sent off to the genetics lab and then they do the genetic analysis. After that, we get the results and then we know which embryo is genetically normal or not.

Host: Excellent. And can an embryo be harmed in any way during testing?

Dr. Alvarez: That is a very important question. And I do get asked that a lot. As far as we know, the embryo is not harmed by the process of doing PGT, doing the biopsy. We have compared embryos that have been biopsied versus not biopsied and they have the same cell survival. They have the same pregnancy rates. So, if there was a negative impact of PGT we would see that either the embryo is not surviving or lower pregnancy rates than a fresh embryo transfer or an embryo that wasn't biopsied.

Host: Is the PG done at an IVF laboratory or elsewhere?

Dr. Alvarez: So, the start of the PGT process, it started in the IVF lab. The biopsy is done in the IVF lab. And then we actually send majority of IVF labs, they send off the tissue to a genetics lab, and they're the ones that do the analysis.

Host: And how does adding PGT to an IVF cycle alter the timeline?

Dr. Alvarez: It does alter the timeline by delaying the transfer of the embryos. So, normally if a couple is not going to do PGT, we do the stimulation, the IVF part, we do the egg extraction, fertilization and then growth of the embryo. And then five days after the egg retrieval we can do, what's called a fresh embryo transfer where we take the embryo out of the laboratory and we transfer it directly into the uterus. Because it takes time to do the genetic analysis, we have to do the biopsy of the embryo, freeze the embryo, and then we get the test results in about two weeks. So, for patients who are going to be doing PGT, they're going to be doing, what's called a frozen embryo transfer. And the timeline then is offset by about a month and a half.

Host: That's significant. Can you give us a list of the benefits of PGT?

Dr. Alvarez: Yes. Well, the number one benefit is to weed out the embryos that are genetically abnormal. We do a grading of the embryo. So, once the embryo gets to day five, we grade the cells either A, B or C; A being the best quality, C being the worst quality. We do know that there is some correlation between the embryo morphology or the grading and their genetics, but it's not 100%. So, the benefit would be to not only select the best embryo based on, looking at it, grading it, but then also knowing the genetics of the embryo. That's the biggest benefit. You would have less embryo transfers. For example, I usually give my patients let's say that you had five embryos and two of them were normal. So, we have potentially reduced the timeline by not having to transfer those three embryos that were abnormal, that will not lead to a pregnancy, would lead to a miscarriage. And then only focusing on the embryos are the most viable.

Host: Sure that makes perfect sense. And what are some downsides to pursuing this treatment?

Dr. Alvarez: Well, there are several downsides. One would be if there's no specific medical indication for PGT, then we're just really delaying time to pregnancy. The other downside would be that sometimes even when we do a perfect biopsy, we don't get a result. So, even if we send out the cells to the laboratory, sometimes they can get degraded, the DNA can get degraded. And so, when they do the analysis, they don't have enough material to be able to do the analysis of; some embryos, come back as no results. And so, with that, then you have the question of, should we transfer or should we not transfer, rebiopsy? And that's something that has to be discussed with your doctor of course, but the downside would bethrowing away embryos that we could have transferred.

The other downside that we have been seeing is that there's a condition called mosaicism where not the entire embryo is genetically normal, but only part of it. And so we're still trying to figure out if mosaic embryos are viable, would they lead to a normal pregnancy or are they also genetically abnormal? And so there's been a surplus of embryos that we've been not transferring because of the results of the PGT that otherwise would have been transferred.

Host: So interesting. Now is this covered by insurance?

Dr. Alvarez: So, PGT-A for aneuploidy, it is not covered by insurance, even if it is indicated by female age. Some insurances will cover the PGT-M for monogenic diseases. Because this is for a specific gene disorder, but usually they're not covered.

And what are the costs involved?

So, it does add up costs to the cost of the IVF. You have the cost of the biopsy and then the cost of freezing the embryos and then the cost of doing the genetic analysis. You also add in the cost of a frozen embryo transfer because you're no longer able to do a fresh transfer, which is included in the cycle of IVF. So, you're adding several points of costs by adding PGT.

Can you share some anecdotal examples of patients who've used PGT and been successful?

Yes, I have many, many patients who use PGT for many, many different reasons. One couple that comes to mind would be a young couple less than 35 where we did fairly good ovarian reserve and she got great number of embryos, but only two of them were genetically normal, which is rare. Like I said, only about 30% of embryos will be abnormal with somebody who's less than 35, but with biology, anything can happen. And so, we were able to get her pregnant right away by transferring the best genetically normal embryo. And now the baby's like one years old.

Host: Oh, i love it. That's wonderful. Doctor how about some words of hope for our listeners?

Dr. Alvarez: Yes. What I want to say is that the field of IVF is growing. We've come a long way since the first IVF baby and things are only going to get better. We're going to be able to treat different diagnoses and have much better pregnancy rates than we have now. So, things are just getting better.

Host: So glad to hear it. Well, this is some enlightening information and hopeful too, Dr. Alvarez. Thank you so much for being with us today to share your expertise.

Dr. Alvarez: Thank you.

Host: That was Dr. Juan Alvarez, a Reproductive Endocrinologist at Fertility Centers of Illinois. Find out more about the services FCI provides for patients by calling (877) 324-4483. Or visit us@fcionline.com to schedule an appointment with Dr. Alvarez. And if you enjoyed this podcast, you can find more like it in our podcast library and be sure to give us a like, and a follow if you do. This has been The Time to Talk Fertility Podcast. I'm your host, Deborah Howell. Have yourself a terrific day.