Melanie Cole (Host): Welcome. Today on Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey, we're discussing genetic testing on embryos. When is it indicated? I'm Melanie Cole and joining me is Dr. William Zeigler. He's a Specialist in Reproductive Endocrinology and Infertility, and he's the Medical Director of the Reproductive Science Center of New Jersey. Dr. Zeigler, always a pleasure. So, tell us about preimplantation genetic testing. What is it?

Dr. William Zeigler (Guest): Pre-implantation genetic testing is we we're able to test embryos for genetics prior to us transferring them into a woman's uterus. And this is really indicated for those patients that have experienced recurrent pregnancy losses, especially in those that have a genetic cause like a balanced translocation, or if they've had a child in which they've may have had with a chromosomal anomaly, or if they've given birth to a pregnancy with a genetic defect, and if both partners test positive for a genetic disease like cystic fibrosis, or spinal muscular atrophy or fragile X. So, we're able to determine which embryos are best suited for transfer based on genetics.

Host: How cool is that. So, while I was doing my research, Dr. Ziegler, genetic testing for embryos can be a bit of a controversial issue, but when women use this screening process, especially older women and women that you've said are indicated, who have had maybe repeat miscarriages, are they less apt to miscarry implanted embryos? Is there data from studies that show that certain methods for genetic screening show higher IVF success rates?

Dr. Zeigler: Well, there is some data out there to show that in those women who are older, where we start running into genetic abnormalities in women with advanced maternal age, that one of the most common causes for miscarriage is genetic abnormalities. So, if we can screen embryos and we can transfer genetically competent embryos, we can increase their pregnancy rates.

Host: Wow. That's really amazing. So, are all genetic testing on embryos considered equal? Are there different types of pre-implantation genetic testing?

Dr. Zeigler: Yes. There are. There's different technologies which are out there. And it all depends on what are we checking for? So, you can do pre-implantation genetic testing for just what are called monogenetic disorders, and which these are called single genes disorders, such as Huntington's disease, cystic fibrosis, or fragile X. That would also help determine those that have autosomal dominant or recessive genetic abnormalities, or even X-linked genetic diseases.

And then we can go into structural rearrangements of genetic material that may actually pose patients to have pregnancy losses such as translocation where genes are basically flipped or inversions or deletions or insertions wear genes should not be. And we can actually create a probe to look for that specific sequence so we can make sure that the pregnancies or the embryos we're putting back in pregnancies we are helping establish have a good chance in surviving and carry to term. And then we have the most common is basically screening for what's called aneuploidy. And this is where we check for all the chromosomes, all 22 pairs, as well as the X and Y. So, we can look for Down Syndrome or Edward Syndrome, which is Trisomy 18 or some of the other trisomies or even those that are Turner Syndrome where you're missing an X chromosome. So, that's one of the most common procedures in which we do when it comes to pre-implantation genetic testing is checking for what's called aneuploidy.

Host: So, then how do you decide which ones to do for which patients and tell us how these PGTs are performed.

Dr. Zeigler: Well, it really comes into play of what is the patient here for. If they're having pregnancy losses and we find that they have a structural abnormality, like a translocation, then we will go down that path, and create a probe. If they're here because they're both carriers of cystic fibrosis and they don't want a child that has cystic fibrosis, well, then we check for the cystic fibrosis gene. In some cases we can do two different types of testing at one time, like we can check for a single gene disorder, like cystic fibrosis, and then we can also check for aneuploidy, which is checking to make sure that all the chromosomes are there. Like there is no Down Syndrome or Trisomy 21 or anything like that. So, at that situation is where we talk to the patients, the pros and cons of doing this because even pre-implantation genetic testing does not test everything in an embryo. All we are doing is we're pulling off around five cells off of an embryo, which is, five days old. At that time, there's only around a hundred cells within the embryo and we're only pulling off five of them. So, we are checking for genetic material in the nucleus, but there's other things that are in that cell.

If you remember back to biology, 101. And I know I'm probably going to be bringing back some bad memories for some people, but you have what are called the organelles. You have the mitochondria, the ribosomes, the golgi apparatus. That's the mechanical part of the cell. And we do know there's DNA in the mitochondria. So, there's been some animal studies that have shown that if the nucleus is normal, the mitochondria may not be, but we are not to that point in which we can actually test for DNA within the mitochondria. But when we biopsy the embryo, like I mentioned, we pull up five or six cells and that's usually after five or six days in culture.

And then we freeze the embryo and we send those cells off for analysis, and then we get the results back and the results will help us determine that even though an embryo looks good, it may not be genetically normal. In doing pre-implantation genetic testing, we do have to let patients know that there is basically a 1% chance that we could actually cause harm to an embryo. But the chances again are low and you have to look at the risk benefit ratio for the couple.

Host: Well, I guess the big question Dr. Zeigler is with any genetic testing, when we're talking about some things to consider before a couple proceeds with genetic testing before an IVF procedure, or whenever they do this, what is it they do with the info? How do you counsel them on what if and what they find out?

Dr. Zeigler: When we get the information from the genetics center, or even prior to that, we talk to the patients of really why are they doing this? And in some cases, it is for, as we refer to as family balancing. There are some couples that do go through preimplantation genetic testing because they have a boy at home and now they want a girl or vice versa or they want the same gender, or they want to have a specific gender first.

So, we do counsel them with regard to, okay, you're going to get this information. What if it's not the gender you want? What if, we don't have any of the gender you want? And we do go through extensive counseling of what to do with those embryos, but we also have to keep in mind that one of the other reasons why we do pre-implantation genetic testing is to reduce the chances of multiples. In the past, when we were not able to biopsy embryos, then we transfer two or more embryos and therefore it increases their chances of twinning to at least 40%. When we transfer a single embryo, one that's biopsied, we know it's genetically normal, we do give the patient the same pregnancy rates or even higher depending on their age, but the chance of having twins at that time is only one to 2% because that embryo would need to split.

So, another benefit of doing pre-implantation genetic testing, we go through this with couples, that when they do this procedure that they have to realize they're not going to be getting transferred the same number of embryos as they may read online that someone has three or four embryos transferred. But in this situation, if we know the genetics of that embryo, we are only going to be transferring one embryo.

Host: Wow that's so interesting. What a great explanation. As we wrap up Dr. Ziegler, and you're just such a wealth of information. What would you like couples to know about preimplantation genetic testing, making that decision and discussing it with a professional, such as yourself?

Dr. Zeigler: Well, you have to realize that preimplantation genetic testing is not for everybody. It shouldn't be offered to everybody because it's not indicated that way. You really need to take a look at the couple. And those are over the age of 37, 38. Yes, there is data out there to support that pre-implantation genetic testing can improve their success rates with assisted reproductive technology. And in those patients that have a history that would indicate that this would be beneficial. But it should not be offered across the board to everybody. Yes. You can discuss it with the patient, but you should also preface it that in some cases, there is no medical literature out there to support the use of pre-implantation genetic testing across the board.

Plus insurance doesn't cover it. And when we talk about price, if someone is paying for their IVF cycle out of pocket or self-pay, you have to figure you're going to tack on another three to $5,000 for just doing pre-implantation genetic testing. And for those that have insurance coverage, insurance doesn't pay for pre-implantation genetic testing.

So again, there could be a financial burden also on the couple and that has to be discussed at the time of our consultation.

Host: Wow. It's really a lot to consider. You've given us such great information. What a great guest is always. Thank you so much, Dr. Zeigler for joining us today. And that concludes this episode of Fertility talk with RSCNJ, the Reproductive Science Center of New Jersey. For more information, you can always visit fertilitynj.com to get connected with one of our providers. I'm Melanie Cole.