Deborah Howell (Host): The embryology team plays a critical role at Fertility Centers of Illinois, but you may not have a lot of face time with the embryology team. They're working hard in the lab to help you grow your family now or in the future. Today, Dr. Juergen Liebermann, Director of Laboratories at Fertility Centers of Illinois, joins the Time to Talk Fertility podcast to discuss embryology and how his team supports you on your fertility journey. This is the Time to Talk Fertility podcast. I'm your host, Deborah Howell. Dr. Liebermann, so nice to have you with us today.

Juergen Liebermann, PhD, HCLD: It's my pleasure. Good morning.

Host: Good morning. Now, what does an embryologist do and why is this role extremely important to a fertility clinic?

Juergen Liebermann, PhD, HCLD: Being an embryologist is an occupation that was coming out of the infertility treatment 20, 30 years ago. It's a very specialized occupation, that deals with the gametes of a couple seeking infertility treatment and parenthood later. So we work with, male gametes as well with female gametes, oocytes, and sperm.

We, create a culture system to fertilize oocytes and make possible they develop to embryos with a potential to achieve pregnancies. We transfer these embryos, we retrieve and find eggs after oocyte retrieval, and we also freeze the oocytes and embryos as well. We do biopsies required to do a genetic testing on embryos.

Host: Sounds good. Now can you tell us about your team and what sets FCI apart from other laboratories?

Juergen Liebermann, PhD, HCLD: So my team, contains about 13 embryologists, two clerks for andrology, and one is responsible for shipping in and out embryos and oocytes. What's special here, we treat each other with respect. We have a very, good work environment. People like to come to work. We appreciate everyone's work and input, so we create a workplace where people, love to work And also bringing their diligence and their focus on the work. Cause that is very important. We train our people in-house. We have a variety of people with different experience that goes from one year to more than 20 years.

And, uh, the benefit of being at, Fertility Center of Illinois is our size. We do more than 2300 retrievals a year and 1600 FETs. We fit volume. We do many cases, literally in a week that overlaps my way to in a month.

Host: Wow, that's wonderful. So, how does FCI freeze and thaw embryos? I'm curious. And does the method of thawing impact success rates?

Juergen Liebermann, PhD, HCLD: It does. Freezing embryos is a powerful tool as an add on to an infertility treatment cycle. And the reason is that when we have a patient that gets stimulated and we retrieve oocytes and we generate embryos; we usually make more embryos as we like to transfer because our first target is, making patients pregnant with a single healthy baby.

So we want to prevent as much as we can multiples. So when she has more embryos after transfer, we have this opportunity to freeze them. They get cryopreserved at a very low temperature. It's usually a liquid nitrogen at a temperature of minus 196 degrees Celsius. And, when we thaw them and patient would come back using these embryos, they have literally the same potential as fresh embryos to generate a pregnancy. We use vitrification. More than 20 years, I was very much involved in this technique, and I also published two books on this. It's a very fast technique that allows us to freeze embryos fast, but also consistently with an excellent survival and after thawing, keeping their potential to make babies.

Host: Sounds great. And about how many eggs does FCI freeze every year?

Juergen Liebermann, PhD, HCLD: So we do about 400 egg freezes a year, but it comes down to an average per patient of 10 eggs, so about 3,500 to 4,000 eggs.

Host: That's impressive. And what role does an embryologist play during an IVF procedure?

Juergen Liebermann, PhD, HCLD: There is a couple of duties everyone has to learn when you come to us. It starts simple with paper work and bloodwork because as an embryologist, we also have to make sure it's a day before that patients have the requirements to retrieve them. That would be the blood work. It's up to date. We have to know it's an infectious disease or it's not an infectious disease.

We go and vent the culture and the storage of the embryos would be in a different tank. We retrieve the oocytes, we will find them with the microscope. You prepare them for fertilization. We do the fertilization. When we check on fertilization the day after, and when we just look at embryos on the day of transfer, we evaluate them, we do biopsy, we freeze eggs and embryos, we also freeze sperm and testicular tissue.

And when the patient comes in, we do also the transfer.

Host: Got it. Now I'm curious, what is ICSI?

Juergen Liebermann, PhD, HCLD: So this is a shortcut for, it stands for intra cytoplasmotic cell sperm injection. So intercellular sperm injection for the child. That means we take a glass needle, we pick up one single sperm and we inject it inside the cytoplasm of the oocyte. So this is one option how to fertilize oocytes. It is definitely very helpful if we have a low sperm count. Another option would be if we create a suspension of sperm of the partner and add it to the oocyte, keep them overnight in culture and let them fertilize by themselves in the dishes.

Host: Understood. And then what happens after fertilization in the early stages of the embryo?

Juergen Liebermann, PhD, HCLD: So when we do fertilization, is it ICSI or conventional IVF, as I explained before, it takes overnight, 18 to 20 hours to determine if this egg is successfully fertilized after sperm injection. After fertilization, they will cleave two, three hours later to a two cell stage embryo, and then another, hours, like, 34 hours post ICSI, it gives a three and a four cell embryo, and so on.

On day three, we will have an eight cell embryo that contains eight blastomeres. We call them blastomeres. And then on day five, we get to a stage where it's very different to day three, because now we just call it also blastocyst, but it contains now more than 150 to 200 cells compared to a day three embryo with eight.

Host: Wow, grows very quickly.

Juergen Liebermann, PhD, HCLD: It grows very quickly, and this very fast growing, happens on day four to day five. It's also a very important step in embryonic development, not just in human, because many embryos can come to an arrest in their development after day three. So when we go to day five and we culture longer than day three, we can see the true value of an embryo because when embryos qualify or disqualify themselves for transfer or for freezing.

Host: Okay, we've been talking about blastocysts. Could you tell me what exactly is a blastocyst?

Juergen Liebermann, PhD, HCLD: So a blastocyst, maybe let me start on day three because on day three, when I mentioned before we have an eight cell embryo, this embryo has we call it totipotency. That means all these eight cells in this embryo have the same potential if we would separate them to make babies. This totipotency gets lost on day four to day five because now these eight cells differentiated in two different cell lines.

One would be trophectoderm and one would be the inner cell mass, we call it ICM. And this inner cell mass is actually the fetus, where the trophectoderm cells will make later the placenta. So, by specializing them now into different cell lines, they will lose their totipotency and they're now pluripotent.

The difference also is of course is the number of cells that we now have, 150 to 200 cells. We have about 120 cells of trophectoderm cells. It's one cell line surrounding the embryo when we have inside cavity, we call it blastocyst. It's filled with fluid. And then we have very isolated, very dense cells of inner cell mass cells, that's the embryo of about 40.

Host: And the difference between Day 3 and Day 5 blastocysts is more than just size, correct?

Juergen Liebermann, PhD, HCLD: It is more than size. On day three, we don't call it blastocyst. We just call it a clevage stage embryo. But then on day five, on day six or day seven, we call it blastocyst.

Host: Okay, got it. Now how does the lab grade embryos and what is the grading criteria?

Juergen Liebermann, PhD, HCLD: We grade based on morphology. So when we look at these blastocysts, or on day three, we look at the size of the blastomeres, or we look at just the number of cells in the blastocysts. We look at their expansion. And, based on this, we grade. So for example, when we create an eight cell embryoon day three, we look at the number of blastomeres.

Is size of these blastomeres equal? Do we have no fragmentation? Sometimes embryos p size where blastomeres create also fragmentation, that can be counterproductive to a good development. Based on this, we grade them, 8 cell 1s or 8 cell 2s if they have more fragmentation, like more than 10 percent.

If we go to the blastocyst, we look at the number of cells, trifectal term, ICM, expansion, and then we give a grading, for example, for expansion, a 1, less expanded would be a 2, and then we get, we provide two alphabetic letters, it's A, for a good cell number. If the number is a little bit less, we give a B.

So a perfect blastocyst, for example on day 5, fully expanded would be a 1. And then we give an A for the number of trophectoderm cells and an A for the inner cell mass. So one AA would be a top rating for a day five embryo. If we have an embryo on day six, that looks like a day five embryo, but it's a day later, we cannot provide any more a one, but we will give a two.

And also if the cell number is correct, AA, so it would be a perfect day six embryo 2 AA.

Host: And that's what we always hope for, right?

Deborah Howell (Host): Okay. Now switching topics just a bit, what is genetic testing of embryos and how is it performed?

Juergen Liebermann, PhD, HCLD: So the genetic testing, we have the ability on a day five embryo or day six or day seven embryo to, determine chromosomes, 23 chromosome pairs, but also the sex chromosomes. So if we have a blastocyst on day six, we open it up. Usually the blastocyst is still surrounded by a protective shell. It's called zona pellucida.

The zona pellucida is very important if couple conceived natural because it's a spot where sperm bind and then penetrates the oocyte to fertilize. In our work here, we have to open up the zona, we use a laser, a small opening and then we go in with a glass pipette, take some cells and pull them out, cut them off with a laser, and it's about 5 to 10 cells from this blastocyst.

I mentioned we have about 120, so it is something, that the embryo can deal with. And these cells go in a little tube and we send it to a reference lab that then looks at these cells, looks at the number of chromosomes, do we have 23 chromosome pairs, do we have not, like a chromosome that is, three times a triple OD.

Or, you is it overall abnormal? So this is genetic testing. At the same moment, we can also determine the sex of the embryo.

Host: Okay. And can an embryo be damaged during genetic testing?

Juergen Liebermann, PhD, HCLD: The only way to get this genetic information, we have to make this opening. We have to take some cells out. There is, a potential to do some damage, but it is just the way how to perform at the moment this technique. Usually our embryos survive very well because of the extreme high number of cells remaining healthy.

So, it is, potentially there, but I can tell you in most cases here, embryos do very well, especially when we freeze them and we thaw them, because they're coming back as normal embryos and we transfer them and make healthy babies.

Host: Good to know. And what new advances do you see in the future?

Juergen Liebermann, PhD, HCLD: For example, we talked about PGD and we talked the potential damage to embryos. So there could be something, we would call it a non invasive assessment of the embryo by not taking cells out, instead of collecting the media, the embryo was cultured after certain hours. And then based on this media, we also can determine the normality or abnormality of the embryo.

So that would be something that would definitely be something we would like to see in future. It has to come from the, labs where they perform genetic testing. It's called noninvasive genetic testing. Another thing I would like to see is, artificial intelligence. And it's something, you know, in future that will impact our field by helping us more to select the right embryo for transfer or for freezing, looking at the number of follicles and determine is it's the right time to give the trigger for the oocyte retrieval.

And then I work intensively on freezing and thawing of embryos. So we always, making progress by making the protocol more sufficient, more time saving, but also more successful embryos. And we will publish that soon in a journal. And we also, I look momentarily on egg freezing also to improve here the outcome in terms of survival and fertilization and how they develop to embryos.

Host: It seems that we're in a golden age of medicine with all the new technology, and it seems like you're at the cutting edge. Is there anything else you'd like to add, Dr. Liebermann?

Juergen Liebermann, PhD, HCLD: I would like to thank you to give me this opportunity to present our work here as embryologists at Fertility Center of Illinois. And, I appreciate very much to have that opportunity.

Host: Well, it's all wonderful information and great news for patients Dr. Liebermann. Thanks so much for being with us to share your expertise.

Juergen Liebermann, PhD, HCLD: Thanks for having me.

Deborah Howell (Host): That was Dr. Juergen Liebermann, Director of Laboratories here at FCI. Schedule an appointment to talk to a fertility specialist at 877-324-4483 or visit fcionline.com for more information.

And if you enjoyed this podcast, you can find more like it in our podcast library and be sure to give us a like and a follow if you do. This has been the Time to Talk Fertility Podcast. I'm your host, Deborah Howell. Have yourself a terrific day.