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Amanda Wilde (Host): It feels so unreal. How can you freeze an embryo without having a child with any problems? We're going to talk all about frozen embryos and pre-implantation genetic testing with Dr. Mary Hinckley. Dr. Hinckley is Medical IVF Director at Reproductive Science Center of the San Francisco Bay Area. This is Fertile Edge, a podcast by Reproductive Science Center of the San Francisco Bay Area. I'm Amanda Wilde, Dr. Hinckley, thank you for joining me. Freezing embryos is still a mysterious process for many of us. In basic terms, how does it work?

Mary Hinckley, MD, REI (Guest): Well, thank you so much for asking. And I'm so excited to have the opportunity to explain a little bit more about embryo freezing so that it doesn't become such a mystery and it's not so unreal and people understand how they can use that to help them build healthy families. So, in general, we freeze embryos in an IVF laboratory after we've helped create those embryos by someone's eggs and sperm, and we can freeze embryos at many different stages, and then they can be frozen for extended periods of time and used at some point in the future to help them conceive.

In general, we've found over the years, that freezing at the blastocyst stage is the best stage for freezing. Because the embryos survive very well from the freezing process. And this freezing process is a complicated one. It actually goes by the true name now, vitrification, which means glass like freezing. So, you may have gone to a fancy restaurant and they served you ice in your drink that was crystal clear and you could see straight through versus some other ice machines that make ice with lots of chips and cracks in them. And that's a little bit what we're trying to do in the laboratory. We're trying to freeze embryos in a very specific way to allow them to have the inner part of that, the cells to be protected, so that, that embryo is protected and the health of the child that comes from that embryo can be protected during the freezing process. So, it's a marvel of science. They have figured out in the laboratory how to use high concentrations of cryoprotectants to dehydrate the cells so that embryos can be frozen in teeny tiny straws. And then at some point in the future, they can be thawed or warmed so that they could be used again and come back to life and be able to divide and become a healthy baby.

Host: So why freeze embryos? Why is that advantageous?

Dr. Hinckley: So, there's lots of different reasons for freezing embryos, but the primary one is that you're not ready to transfer that embryo today. And so originally when we started doing IVF and creating embryos in a laboratory, many people felt the need to have all of those embryos returned to their uterus to conceive.

And obviously if you made more than one embryo and you put two embryos back into the uterus, you could have twins. And if you made three, you could have triplets, and on and on. And so the need was present that if someone was fortunate enough to be able to make more than one embryo, rather than risking the pregnancy by putting multiple embryos into the uterus and creating a very high risk, complicated pregnancy, that it would be better if the extra embryos were frozen and could be used in the future. Now, of course the technology had to be good enough so that embryos could survive this freezing and thawing. So, the primary reason was what do we do with the extra embryos that come from an IVF cycle. But now we've found that because this technology works so very well, we can use it for many other purposes.

A primary example is someone who might want to freeze embryos for the future because they're not ready to get pregnant at all right now, perhaps they're going through chemotherapy and hoping to get through cancer treatment, perhaps they're going traveling or they have a job assignment or they are back in law school and they need to postpone their childbearing for the future, or perhaps they want to do testing on the embryos. And that testing takes time to get the answer. And so they need the answer before they put that embryo back into their uterus.

Host: What are the success rates with the frozen embryos?

Dr. Hinckley: Well, it varies a lot. And this is the exciting part is that it has gotten better and better with time. So, in our clinic, we can freeze and thaw embryos at the blastocyst stage at about a 98 to 99% survival rate, which means that embryos going into the freezer and through the vitrification process, if we put a hundred in, we can get 98 or 99 out.

Now that's not a hundred and we are still trying to get to a hundred. But the process is pretty solid and secure that very few embryos are going to be lost in the freezing and thawing process. However, the success rate of each embryo depends on the quality of the embryo before it was frozen. And of course, to some degree depends on the quality of the lab that freezes the embryo.

So in our lab, our statistics across the board for a good quality embryo are about 70% success rate. Meaning about 70% of those embryos become babies. But we can further break that down based on what is the quality of the embryo in terms of its grade. Cause so it gets a grade much like we did when we were in school.

We can determine its success rate based on whether it was genetically tested and found to be chromosomally normal. Those embryos do very well as in addition, if they're able to be frozen and survive the thaw and transferred. And then there are other factors, if the embryos aren't tested that have to do with the success rate, such as the age of the woman, the health of the sperm, the quality of the uterus, but in general, blastocyst embryos have a much higher success rate than embryos that are frozen at the earlier stages at the two cell stage or the eight cell stage, the day three stage, which was commonly done for years and years now, we've learned by waiting till the embryo gets to the blastocyst, we have higher success rate with those embryos.

Host: So that's the best time to freeze embryos. What is the best time to thaw the embryos?

Dr. Hinckley: Oh, well, that's exciting. So, the best time really depends on you or depends on the patient. When are they ready to have their family? And we always encourage people to think about that and to recognize that there is no perfect time, that your life circumstances can change, that if you're feeling oh I need to wait a little bit longer till my job is stable or my pay is stable or until we have a bigger house, that really there is not the perfect time. And that sooner is better because that way you have more flexibility if things don't all go the exact way you had anticipated. So for example, if I have someone who's chosen to freeze embryos for the future, because they were not ready to have a child at that point in time, I like to encourage them to still try before it's too late to try again. So, not to wait until they're 42 or 43 to thaw their embryos, but instead to maybe consider a little earlier so that if for some reason they aren't in the lucky 70% that get pregnant with that frozen embryo, they still would have an opportunity to have to try in other ways to have a family.

Host: That sort leads me to this next question. How long can a frozen embryo remained viable? I mean, does a frozen embryo have a best by date?

Dr. Hinckley: Oh, that's great. Well, actually, each of those little straws do have dates on them. They have the patient's name, their medical number. They have, they have quality control stamps that we can watch them, but there isn't really a best by. So, embryos can be frozen as long as there is liquid nitrogen in the tank and the tank is kept safe and secure.

And so for practice, one of the oldest embryos that's ever been thawed and subsequently used to create a baby was in the cryoprotectant for over 19 years. But there have been reports even in this last year or two of embryos that have been thawed after being in the freezer for 27 years and then subsequently the patient who had the baby from an embryo that had been in the freezer for 27 years, decided to come back for another child, the other embryo and had a child from an embryo that had been in the freezer for 29 years. So, it is fascinating technology that life can be stopped and then restarted at a point in the future and a healthy child can result.

Host: Now see, even like 29 years ago, pre-implantation genetic testing probably didn't even exist. Can you describe the connection today between in vitro fertilization and pre-implantation genetic testing?

Dr. Hinckley: Yeah. Good question. So, back 29 years ago, a lot of the embryos were frozen at an earlier stage at a day three stage, or maybe even at a two cell stage and testing wasn't done because it wasn't available, but that doesn't mean that embryo wasn't healthy and normal. And if it was frozen and care was taken through all the years, it can still be a beautiful, healthy baby. Today though, we use some of the other technologies to help improve the success of embryos that we transfer by understanding more about the quality of that embryo. So, we can do testing such as PGT or pre-implantation genetic testing. And this testing allows us to check the chromosomes to make sure that the embryo is chromosomally normal. Embryos that are chromosomally normal, have a higher chance of being healthy babies. So, by knowing that the embryo is normal, you have a higher chance of knowing that you would be able to get a baby from that embryo, at some point in the future. Therefore many patients who are freezing embryos for the future, they are banking them, like to do the testing on the embryos ahead of time so that they know what they're freezing really has good chances. They don't want a lot of embryos frozen, not knowing if they're going to be a healthy baby or not. They'd rather have a smaller number frozen where they know, have a very reliable success rate when they go to be thawed and transferred.

Host: So is PGT recommended for all patients.

Dr. Hinckley: It is not. And so this is a very controversial area right now. So you're asking a very timely question, as we understand more about PGT and the benefits and truthfully the disadvantages. And so this is something where a really careful conversation with your doctor can be helpful, looking at a patient's unique needs. For women who are older and by older, I they're all younger than me. So, for women who are older and by that, I mean maybe, you know, 38, 40, 42, what we find is that a lot of the embryos that are created, even embryos that look absolutely beautiful under the microscope, may not be chromosomally normal.

And that's why in general, as women age, they have a higher chance of infertility and a higher chance of miscarriage. But if they're able to make a chromosomally normal embryo, then their miscarriage rate is no higher than a young woman who makes a chromosomally normal embryo and their live birth rate is exactly the same as a young woman who makes a chromosomally normal embryo. And so for older women, testing is really helpful because if they only froze three or four embryos and it happened to be that all of those embryos were abnormal, they need to know that now and have the opportunity to perhaps do more cycles and freeze more embryos. On the other hand, if they made great embryos in their very first cycle, they don't need to do cycle after cycle the store more embryos, they have plenty. And so for that group of patients, the testing is really helpful. For women who have a genetic disease or couples that have a genetic disease, the testing is helpful.

But for young women, especially women, less than 35 who are conceiving or attempting to conceive and create embryos, those women may not really need to do the testing. And since the testing is not a hundred percent certain; the testing may not really help them achieve a higher live birth rate. They may have to understand and accept that some of their embryos will not work to create a baby, but if they have enough embryos frozen and they understand that, and they accept the fact that sometimes the transfer may not work to create a baby or sometimes and in lower percentage of chances cause they're younger; they may have a miscarriage, then they are often more accepting of not doing the testing, not having to biopsy the embryo, not having to take a chance that the biopsy is wrong and will just freeze embryos without the testing. And that's perfectly acceptable and a very valid way to proceed. And so we often will talk about those choices with women and couples and help them make the best decision for their unique situation.

Host: Yeah. So every individual situation needs to be considered. You talked about age being a factor. What other conditions should be considered if you're thinking about having PGT, the pre-implantation genetic testing?

Dr. Hinckley: Yeah, I think age is the primary one and goals. I mean, there are couples who have unfortunately gone through a very tragic situation where they've been pregnant and had a baby with a chromosomal problem. And so therefore they really want to try to avoid that in the future. There are some couples that if they found out they had a child with a chromosome problem, they would not continue that pregnancy and they would have to terminate the pregnancy.

And that can be very challenging. For example, if someone had a pregnancy where there was Down syndrome and they chose to terminate that pregnancy, that might be a very hard choice. And so they might rather do that testing before so that they knew what the odds were in that situation. Those are indications for it.

Other than that, it can sometimes come down to insurance coverage. Sometimes come down to the quality of the lab that you're using, where you freeze your embryos, medical diagnoses, not so much. So if someone say, for example, if the reason that infertility is tubal infertility or poor sperm, or even polycystic ovarian syndrome, PCOS, that's not so much of a reason to necessarily do pre-implantation genetic testing. However, that could be a very important reason to do embryo freezing. For example, women who have PCOS tend to over respond to the medicine we use to freeze embryos. And if they over respond to the medicine, it can make it much more dangerous to do a fresh embryo transfer and have them get pregnant because they could develop ovarian hyperstimulation syndrome.

And so for this reason, we often encourage women who have polycystic ovarian syndrome or who have an elevated AMH hormone level, to freeze their embryos, to go through the initial cycle, create and freeze embryos, let their body cool off and their ovaries get back to normal size and make sure they've adjusted and then transfer the embryo the following month when we know they'll have a much lower risk of having ovarian hyperstimulation or complications in pregnancy.

Host: It sounds like in vitro fertilization has come a long way in terms of identifying specifics, and I assume therefore, bringing up this success rate, is there anything else you want to add about fertility, frozen embryos or PGT?

Dr. Hinckley: It has come a long way and it's been really exciting because the field of fertility is only a little over 40 years old, and RSC has been one of the clinics on the forefront of embryo freezing. And we're really proud of our history and excellence in that. There are awards that are given to certain clinics every year. And our clinic has often received those awards for embryo freezing. So, I think RSC, especially, has focused on this and how it can be used to help patients. I think in general, I just want to encourage patients to not be afraid of the technology of embryo freezing, to understand that there are risks and benefits, but to use those benefits to their advantage so that they don't feel the need to transfer multiple embryos and have a triplet pregnancy, which could have very worrisome outcomes of prematurity for the babies. So, that they know they don't have to discard embryos and they can instead freeze them for the future to be able to attempt to have a second or a third child and that they can use it to keep their IVF cycle safer so that ultimately they can create the family they desire in a safe and healthy way.

Amanda Wilde (Host): Perfect. Thank you, Dr. Hinckley. For more information about PGT and in vitro fertilization, please visit rscbayarea.com/treatments. And if you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you. This is Fertile Edge by Reproductive Science Center of the San Francisco Bay Area. I'm Amanda Wilde. Thanks for listening.