Melanie Cole, MS (Host): Welcome to Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey. I'm Melanie Cole and today we're highlighting pre-implantation genetic testing. Joining me is Dr. William Ziegler. He's a specialist in reproductive endocrinology and infertility. He's the Medical Director of the Reproductive Science Center of New Jersey, and he is the Chairman of the Reproductive Endocrinology division at Jersey Shore University Medical Center.

Dr. Ziegler, it's such a pleasure to have you with us today. So PGT, pre-implantation genetic testing. Tell us what that is, when it was first used. How does it help infertility treatments?

William Ziegler, DO, FACOG: Well, pre-implantation genetic testing was first used in 1990 and its purpose was actually to identify X-linked disorders. Since that point in time, over 50% of IVF cases, are utilizing pre-implantation genetic testing. And so it has evolved from just being testing for only one disorder or one condition to now it's branching out into many other conditions.

Host: Isn't that fascinating the field you're in, Dr. Ziegler. I'm always amazed at what you have to come here and tell us. Now how does this work?

William Ziegler, DO, FACOG: To undergo pre-implementation genetic testing, we really need embryos. And the only way that we can do that is to go through in vitro fertilization. And this involves a patient taking injections of fertility medication, and we monitor the follicle growth until they get to a certain size that we are pretty sure we're going to be getting mature follicles or mature eggs, I should say. And then they would go for a retrieval, which is a procedure that takes around 15 or 20 minutes within the office. Patients are given IV sedation. They're kept very comfortable for this procedure. Once we have out the eggs, we then fertilize them. The embryos are monitored in our lab to day five or day six. At which point in time, they undergo an what's called a trophectoderm biopsy, and that is where we make a little opening in the shell around the embryo and we slowly pull out only five or six cells and we use a laser to help us identify the juncture between cells so we don't injure the cells and we take them from the trophoblast because that's going to become placenta.

We don't take them from the cells that are going to become embryo. So once we have out those cells, they are then fixed to a slide and we send them off to our genetic center, at which point in time, the result comes back to us within around two weeks. And we can tell a patient whether an embryo is genetically normal, whether it has Down Syndrome or some other trisomys. We can tell patients even the gender, so in case they want to have a boy first or a girl first, or whether they want to do family balancing, we are able to give them that information. So they can make the appropriate judgment call for their family.

Host: As I understand it, Dr. Zieglar, there are different types of PGT testing. Can you tell us about those?

William Ziegler, DO, FACOG: Yeah. Initially it started off as PGT-S, which is pre-implantation genetic screening, and then it went to pre-implantation genetic diagnosis or PGD, that's where we're looking for specific genetic abnormalities like cystic fibrosis or sickle cell. Over that time, things have kind of changed. And now the terminology of PGT-A, which is pre-implantation genetic testing for aneuploidy and those we usually do in those patients who are older, those that have a higher incidence for Down Syndrome or other genetic trisomys.

So we check for all 46 chromosomes as well as the two sex chromosomes. Then you have PGT-M, which is checking for a specific mutation, like I mentioned before, like cystic fibrosis, or Huntington's or one of those genetic abnormalities. And now we have PGT-SR, which is structural rearrangement, which is basically for those that have what are called translocations, it's where the genes are flipped or there's a deletion, they're missing a gene, or they have an extra gene in which we need to identify. So over the time this has kind of evolved, including the technology in doing this. We went from fluorescent in situ hybridization, where we identify a segment of genetic material and we can put a tag that looks for that specific sequence. And when it lights up, it tells us, that sequence is there. And then we moved from there. We went into CGH array, which is where we're actually using a computer to look for, making sure that all the genes are lined up the way they're supposed to be. And now we're going into what's called snip technology. It's more precise in identifying genetic abnormalities within an embryo. So our field in regarding this perspective has really jumped by leaps and bounds.

Host: You explain everything so well, Dr. Ziegler, you really make it so understandable. What are the benefits of undergoing PGT testing before embryo transfer? How does it contribute to success rates of fertility treatments like IVF? What do you tell couples when you're talking about this with them?

William Ziegler, DO, FACOG: When we talk to couples about pre-implantation genetic testing, it is not for everybody. It's really indicated for those that have medical indications for it. Even in those women who are over the age of 38, we advocate for it because the probability of having a genetically abnormal embryo is more than 50%.

So therefore, we talk to them about pre-implantation generic testing. We talk about the benefits that does increase their implantation rate, their live birth rate. It lowers their miscarriage rate. Also, for those that, who've had a genetically abnormal pregnancy in the past; they don't want to get pregnant and wait until 13 or 14 weeks until they find out whether the baby is genetically normal or abnormal.

So this is a way for us to help mitigate that possibility as well as to decrease the stress that a patient may be undergoing, worrying about the genetics of the pregnancy, which they're carrying.

Host: That makes so much sense and it must be so calming, more calming for couples that are so concerned about those genetic abnormalities. Are there any risks or limitations that are associated with PGT that you let couples know about?

William Ziegler, DO, FACOG: Yes, we talk about that since we're only pulling off five or six cells. So we have a limited number of DNA to basically look at. There's always a possibility for false negatives. so there could be normal cells on one side of the embryo and abnormal cells on the other side, and those are called mosaics.

That is where you have two different cell lines in one embryo. So those are some things that, we sometimes cannot detect. Also damage to the embryo. When we are pulling off these cells, we're being as gentle as possible, but sometimes these embryos do not survive the biopsy, freeze thaw process.

So we do talk to patients. There are risks to this and therefore we'd like to have an indication to do it. But now, because it's so cost affordable for patients to do it; it's not $8,000 anymore. It's more reasonably priced that a lot of patients say, I don't want to take that risk.

I'm going through IVF, I will pay extra for this other testing. So, we do talk to patients about the risks and they have to feel comfortable with making that decision.

Host: Dr. Ziegler, this is such a forward thinking field of medicine you're discussing here today. Are there future exciting developments that you'd like to mention or talk about and any ethical considerations that you talk to patients about before they go through with this.

William Ziegler, DO, FACOG: Well, what's new on the horizon at this point is, they're getting more sophisticated with genetic testing and they're coming up with what are called testing for polygenic disorders. Such as arrhythmias, for diabetes, for Parkinson's, to the point that you can get a profile of what is the risk that your embryo is going to have Parkinson's, or that your child in the future is going to have diabetes.

So, that's something that's on the horizon. It still is not standard of care, but I think it's something that is coming down the pike. But then it comes down to, as you were mentioning before, what are the issues that we need to talk about ethically? Well, even though the pregnancy or the embryo may be at a higher risk or a lower risk for diabetes, it may be at a higher risk for Parkinson's.

So, you need to do a give and take. Okay, which is worse. Also, I'm thinking that this may come down to an a la carte type situation where if diabetes runs in your family, maybe checking the embryo for its risk for diabetes, instead of doing like a shotgun approach and checking for all different types of diseases in which can be ranked; is to tailor it to the couple and to the situation, so we can better identify which embryos are the best ones to transfer, which has a lower risk for that specific disease. Because it's going to come down to where we're going to need to have some guidelines into what is an acceptable risk and what is not.

And to date that is not out there. But I think this is on the horizon for us to venture into.

Host: That makes so much sense. So as we wrap up, Dr. Ziegler, for patients considering fertility treatments, what advice do you give them regarding the role of genetic testing in their journey of fertility and why it's so important that they discuss this with you when making that important decision?

William Ziegler, DO, FACOG: I think patients need to know the limitations of this technology, and what are they going to do with this information? Is it really going to change their decision making process? Keep in mind that any procedure we do on gametes or on embryos, there are risks. Even if we biopsy an embryo and it comes back to be genetically normal, we thought it may not survive.

So we really need to keep that in mind that there are risks. Plus we can't biopsy every embryo. We can only biopsy high quality embryos. So patients need to be aware of that. They need to be a high quality embryo for us to biopsy or else it's not going to survive. And in going through this, if I tell a patient, oh, now we have after fertilization, we have 10 embryos, that doesn't mean all 10 embryos are going to make it out to the part that we can biopsy.

 And they may not make it there at all. So we need to really put it into perspective that yes, this is wonderful technology, but it does have risks.

Host: That's really interesting. Dr. Ziegler, you always come onto these and have so much information to share, and I can't thank you enough for sharing this kind of information because it can be such a confusing worrying world, infertility and infertility, and you just clear everything up so beautifully.

Thank you again for joining us and for more information, you can always visit fertilitynj.com to get connected with one of our providers. That concludes this episode of Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey. I'm Melanie Cole. Thanks so much for joining us today.