Melanie Cole, MS (Host): Welcome to Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey. I'm Melanie Cole. And joining me is Dr. William Ziegler. He's a specialist in reproductive endocrinology and infertility, and he's the Medical Director of the Reproductive Science Center of New Jersey. And we're here to talk today about embryo transfer, fresh versus frozen. Dr. Ziegler, thank you so much for being with us as always. Can you start by telling us the difference when using frozen embryo versus fresh? What's involved with each? I don't really understand it. So explain it to us.

William Ziegler, MD: Over the years, there's been a lot of debate around fresh versus frozen embryo transfers. And there are benefits that surround both of these. But let me kind of go through what the difference is between fresh and frozen transfers. They both basically start off the same way, that a patient needs to undergo a series of injections for ovulation induction. And we also monitor the cycles. And then, at the appropriate time, we go for an egg retrieval. And at which point in time, the eggs are fertilized with the partner sperm or with donor sperm. And in a fresh transfer, the embryos are growing out to around day three or day five. And then, one is transferred back into the woman's uterus. On the other hand, with the frozen embryo transfers, after they're fertilized, they're grown out to around day five or day six. At which point in time, they're then frozen. And the patient would then need to go through what's called a frozen embryo transfer cycle when she wants to use those embryos.

Melanie Cole, MS (Host): That was an excellent description. So tell us a little bit about the reason that you might have for a preference. Do you have a preference?

William Ziegler, MD: We would prefer to do a frozen embryo transfer cycle versus fresh. However, there are some other factors that you have to really take into account, whether you're going to do a fresh or a frozen transfer. Besides the success rates, which I'll go into in just little bit, there are some other factors to make your decision on. One of them is the patient's age. Because if they're older, they may want to have a fresh transfer or the quality of the sperm or even their overall health. And what's really important is the quality of the embryos which are made. And we know that women who are below the age of 35 have a higher chance for making better embryos than women who are above the age of 35. We know that high quality embryos are associated with a 79% live birth rate. Good quality embryos, 64%. And poor quality embryos are associated with a low birth rate of 28%. So those are some things that you have to kind of take into account when a couple are going through in vitro fertilization. I don't think that you can say you're not going to do a fresh transfer when they have good enough embryos for transferring, but you can't freeze them because they will not survive the stress of the freeze-thaw process.

And the other thing is about success rates. And when you talk about success rates, you can find data all over the place that will tell you fresh is better than frozen. However, there's been a meta-analysis out there that looked at around 54 studies, 12 of them were randomized controlled trials. And what they have found is that fresh transfers are associated with a lower implantation rate, a lower pregnancy rate, lower ongoing pregnancy rate, as well as a higher rate for ectopic pregnancies. So in that situation, we need to really think about if we are able to freeze embryos on a patient, we should do that, so we can really improve the outcome of their cycle.

Melanie Cole, MS (Host): So as you're just saying, you know, about the studies and it sounds to me, Dr. Ziegler, like one size may not fit all, and that what's right for each patient may depend on a variety of factors that might arise before or during their IVF cycle. Can you share any of the factors for people listening? What does the patient have to do for either one of these to be an option? And how does that all work?

William Ziegler, MD: Well, we always do a workup. We always look at a semen analysis. We check for a patient's ovarian age or egg quality. And we also look at uterine factors and tubal factors, and that's how we kind of come up with protocol for them. But there are other benefits that we have to take into account when we are counseling our patients, that frozen embryo transfer cycles are less costly. So they don't have to be re-stimulated, they're stimulated just once and then we can freeze these embryos. Frozen embryos can be stored for years. The oldest embryo that was ever transferred and resulted in a live pregnancy was stored for 27 years. So we know that the freezing process is quite effective. We also freeze embryos for those that are just not ready to have children yet, but yet they're getting older, so it preserves their fertility.

The other is that it's less of a mental and physical stress on a woman's body. In going through a fresh cycle, again, there's multiple injections, multiple visits. And then, there's the retrieval process. When in a frozen embryo transfer cycle, a patient just needs to take medication to thicken their uterine lining and then we transfer the embryo. So it's less stress, but I think part of the reason why success rates are so high, is that a frozen embryo transfer really mimics a natural cycle. In a stimulated cycle, you have very high estrogen levels and they're present even at the time of transfer and this can negatively affect implantation. And in these cases, in some cases, you are putting back multiple embryos. So therefore, they have a high risk for multiples.

The other important thing to keep in mind is pre-implantation genetic testing. If we freeze embryos, we can biopsy them, we freeze them and we can assess whether or not they have a genetic anomaly. We can also tell gender. So for those that are older, now we have minimized their risk to have a genetically abnormal pregnancy, like Downs' syndrome or like a trisomy, something like that, that could affect a pregnancy and can cause a miscarriage.

When we take a look at the complications that a mother and a baby may go through, there is some differences between fresh and frozen. We know that, as I mentioned before, that with fresh transfers, there's a higher risk for an ectopic pregnancy, but there's also a higher risk for a low birth weight infant. As opposed to frozen embryo transfer cycles, it's kind of the opposite. You're at risk for a larger for gestational age infant. But frozen embryo transfer cycles are also associated with a higher incidence of pregnancy-induced hypertension as well as preeclampsia.

So I think there's pros and cons to both. But when we look at birth defects, there's no difference between the two. When we look at academic performance at the age of 15 to 16, in which there's no difference. And there's no difference in miscarriages, miscarriages may be decreased in those that have pre-implantation genetic testing because they're putting back euploid or genetically normal embryos.

So these are some of the things that we have to keep in mind when we're counseling patients and keep in mind their desires. They may have religious conflicts in freezing embryos. So, therefore, we need to pay attention to the medical reasons for doing this, but also the non-medical reasons. Maybe financial could be a factor and, I mentioned before, regarding religion or their ethics or their personal bias. And both partners need to be on the same page in going through all of this.

Melanie Cole, MS (Host): Wow. It's a lot to think about and you've laid it out so nicely. Dr. Ziegler, what about cost and time? Before you wrap it up, speak about those two factors about the time factor involved. You already mentioned some of the mental toll and the psychosocial issues between the two, but what about cost and time?

William Ziegler, MD: Well, when you talk about cost, it all depends whether somebody has fertility coverage or not. And if they have fertility coverage, in most cases, they will cover both a fresh and a frozen transfer. They will not cover pre-implantation genetic testing in most cases. But if it's coming out of a patient's pocket, you'd rather not have them go through multiple retrievals, because those cycles can range anywhere between $10,000 to $15,000. And then, a frozen embryo transfer cycle, the medications we use are not really fertility medications. So therefore, a lot of times they're covered under their major medical policy. And the procedure itself, it's probably running around $3,000 to $4,000. So it's a lot cheaper than going through a retrieval after retrieval after retrieval. So you'd rather, you know, err on the side of freezing good quality embryos at the patient's age now, because if they come back to you in three to four years, they may have an ovulatory problem. Miscarriage rate is going to be higher. Pregnancy rates are going to be lower if we used her eggs at that advanced age versus if we freeze embryos now.

Melanie Cole, MS (Host): This is so interesting. What would you like the key takeaway to be, Dr. Ziegler? When people are asking you these questions about embryo transfer and fresh versus frozen and, like you said, there's a lot of information on the internet, but some of it can be counterproductive to be looking at because really it's weighing the benefits of each against those pros and cons. So wrap it up for us.

William Ziegler, MD: Well, regardless of whether a patient wants to do fresh or frozen or regardless of what they read on the worldwide web, my advice to any patient, what transfer would be best for them should really be discussed with a trusted fertility center with experts within our field. They are the ones that will take the entire picture and tell you the pros and cons of a fresh or frozen transfer, because as you mentioned before, not one size fits all and you really need the tailor a patient's treatment to their desire and to their individual situation.

Melanie Cole, MS (Host): Thank you so much as always, Dr. Ziegler. What an educator you are. Thank you so much again. And for more information, please 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.