Melanie Cole, MS (Host): Are you looking into fertility treatments? We're talking about embryo transfer, fresh versus frozen, today on Fertility Talk with RSCNJ, Reproductive Science Center of New Jersey. I'm Melanie Cole. Joining me is Dr. William Ziegler. He's a specialist in Reproductive Endocrinology and Infertility and the Medical Director of the Reproductive Science Center of New Jersey.

Intro: The Reproductive Science Center of New Jersey combines a commitment to sensitive care with a state-of-the-art program. We proudly present Fertility Talk with RSCNJ. Here's Melanie Cole.

Melanie Cole, MS: Dr. Ziegler, it's such a pleasure to always have you on. So, tell us the difference between using fresh and frozen embryos. What's involved in each?

William Ziegler, DO: When we talk about a fresh embryo transfer, these are patients that are going through in vitro fertilization and we stimulate them with superphysiological levels of hormones that normally come from the pituitary gland. It's follicle-stimulating hormone. And we use something called human menopausal gonadotropin, which basically is similar to luteinizing hormone.

And during the time, they're on these medications, we monitor them very closely. We measure their follicle as well as estrogen levels, and those estrogen levels really go higher than what is normally produced from the ovary. So then, we monitor them. And when they get to a certain point, and they have enough mature follicles, we call it, we then go for an egg retrieval. And that's done through the vagina, and patients are given IV sedation. And then, we retrieve those eggs. And then, we fertilize them.

And there's two different ways to fertilize. One is standard insemination where you take the egg and just surround it with sperm. And the other way is where you physically take one sperm and put it right inside the egg. And then, we grow it out. And we usually grow it out to around day five or day six after retrieval, and then we go for a transfer. Any extra good quality embryos we can freeze. And then, we monitor estrogen and progesterone levels between the transfer day and the pregnancy test day, and then there's the pregnancy test. And that's the way it's been done.

The first retrieval in the first IVF baby was in 1978, which that is Louise Brown. And since that time, our field has really advanced to the point that now we are able to do more assessment of an embryo. We can do genetic testing. However, if we do genetic testing on an embryo, we have to freeze it. And that is where we're moving more towards what's called a frozen embryo transfer. And in doing so, we are able, again, to check genetics of an embryo. So therefore, we know if the embryo has all 46 chromosomes and whether it has two sex chromosomes. So, we can tell a couple prior to a transfer whether they are having a boy or having a girl or they can select which one in which they would have.

But during this transition, going from fresh to frozen, and in a frozen transfer, we don't stimulate the ovaries. All we do is we prepare the uterine lining with estrogen and progesterone. So, we don't get to those really high levels that we normally would do in a fresh cycle. And then, we monitor the uterine lining. It gets to a certain thickness, a certain pattern, and then we do a transfer. And then, we transfer the embryo, and now we're only transferring one embryo, so we reduce the multiple rate.

With fresh, in many cases, we're putting back more embryos. So therefore, we're seeing more high ordered multiple pregnancies with fresh cycles than what we do with frozen. What that does, besides it puts the woman at risk, it puts the pregnancy at risk, but also having multiples stresses the healthcare system. So now, we're putting out more money because patients that have multiples deliver early. They can have complications, hypertension, as well as diabetes. And those babies sometimes end up in the neonatal intensive care unit. And therefore, again, we're stressing the healthcare system.

Melanie Cole, MS: Wow, Dr. Ziegler, I didn't know any of that. And how interesting, now I really understand the difference between the two. This may sound redundant, but do you have a preference? I mean, you just listed the reasons why frozen is safer and better for the medical system and the woman, and you can do genetic testing. Do some people pick fresh for a reason? I mean, do you have a preference yourself?

William Ziegler, DO: We would rather do a frozen transfer. The reason for it is that, number one, that we do get a higher pregnancy rate. There's a lower miscarriage rate. But even down the pike, closer to delivery, those that have a frozen embryo transfer, gestational age is longer. There's a decreased risk for preterm delivery as well as hypertension in pregnancy. For some reason, the frozen embryo transfer is safer for the mom and the baby. So, we do prefer doing frozen embryo transfers.

Melanie Cole, MS: Is there a difference in cost? You know, this may not be the best question, but it certainly is an important question for couples that are looking into fertility treatments.

William Ziegler, DO: Well, there is an additional cost because of the freezing, and they're going to need to undergo a few more ultrasounds for a frozen embryo transfer, and then as well as some blood work. But when you take a look at the success rates, using frozen embryo, you're looking at anywhere between 5-10% increase in pregnancy rates.

So, in that case, doing a frozen embryo transfer is probably worth the cost of a frozen embryo transfer. And now, a lot of times, insurance companies pay for fertility treatment. I know, I believe there's 17 states that cover some form of fertility treatment. And therefore, it's easier for them to make that decision to go for a frozen embryo transfer.

Melanie Cole, MS: How long can embryos be frozen and still be considered viable? And when you do that with the couple, how long do you freeze them before you implant them?

William Ziegler, DO: So, the longest an embryo has been frozen and was transferred and resulted in a good pregnancy was 24 years. And it was transferred into a woman who was 23 years old. So, this embryo came from an embryo adoption back. So, the embryo was actually older than the woman who was carrying the embryo.

Melanie Cole, MS: Wow, that is amazing. Now, Well, obviously, I'm thinking that's not too typical with average couples that you're working with, then the embryos get frozen and then how long until then they're implanted. And do they leave some embryos in the freezer for a while in case it doesn't work?

William Ziegler, DO: Right. Well, normally, after we biopsy the embryos and we freeze them, the patients usually undergo an embryo transfer on a frozen embryo transfer cycle probably within the next two months. However, we do have patients that, again, which they get pregnant and the embryos are still in liquid nitrogen until they want to come back. So, we have patients that have had multiple embryos that are cryopreserved, and they come back to us in a year. And they come back again in like, let's say two years, and then maybe three years, because those embryos, keep in mind, are cryopreserved at the age in which they were retrieved. So if I have a patient who's 30 years old, and I freeze embryos, and she comes back to me at 35, and then maybe at 37, and then at 40, the pregnancy rate and the miscarriage rate is going to be at 30. So, it's at the age in which the eggs were retrieved.

Melanie Cole, MS: That's amazing. I mean, really, what an exciting time in your field, Dr. Ziegler. That is really advanced medicine. What would you like couples that are looking into embryo transfer to consider when they are going through all of this in their head? You've clearly made the case here that frozen is superior for many couples. And obviously, this is a choice for couples, right? And you help them to make this choice while you're helping them to make this choice. What are some important things you want them to consider?

William Ziegler, DO: Well, I know when we meet with patients and we talk about doing a fresh cycle, and they really would like to have a fresh transfer, mainly because of a psychological standpoint. I'm going through all this, and if there is a possibility that I could get pregnant on a fresh cycle, I'd rather be pregnant sooner than later. And just keep in mind that we are able to assess embryos so we can assess them, as I mentioned before, for genetics. So therefore, when they are pregnant, they have some relief that, "Okay, the probability of this pregnancy being genetically abnormal is extremely low, versus getting to where the part where they're getting the Harmony test or the Panorama test, and that's when they take blood from the mother and look for fetal red blood cells, and they check those for genetics, which is around 13 to 14 weeks. You don't want to get the news at that time that, by the way, you are carrying a genetically abnormal pregnancy. You'd rather mitigate that as quickly as possible or as soon as possible.

So, I think when a couple are deciding on whether to have a fresh or frozen transfer, keep in mind the benefits of that frozen transfer, plus it's easier to schedule. So, we know what day. We can tell a patient, this is going to be your day for your transfer. So, it's easy for them to schedule things versus we're stimulating you and you could be retrieved anywhere within a seven-day period. So, I think in that respect, it sometimes takes a lot of stress off of a couple while they're going through fertility treatment.

Melanie Cole, MS: Wow. It certainly does. You've given us a lot. Great information. I mean, you're always a great educator. Dr. Ziegler, you're such an interesting man and so knowledgeable. Your expertise is just unmatched in this field. I thank you for joining us, but today's was really great. That was so informative. Thank you again.

And for more information, please visit fertilitynj.com to get connected with one of our providers. That concludes today's episode of Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey. I'm Melanie Cole. Thanks so much for joining us today.