Forty Years of In Vitro Fertilization

with DR. ANTONIO PELLICER
Dr. Antonio Pellicer discusses his beginnings in the field of infertility and the founding of IVI. Listen in as he discusses the biggest breakthroughs in the history of IVF: from the impact of transvaginal ultrasound to the accidental discovery of ICSI. Hear his vision on what the future holds for IVF and fertility treatments in the years to come.
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Podcast Transcript

Dr. Andres Reig:

The information shared in this podcast does not necessarily represent IVRMA’s stance. These podcasts are not a substitute for consultation with a physician. Hello, I’m Dr. Andres Reig, welcome back to FertiliPod, a podcast where we discuss current topics and the latest research in the field of reproduction with some of the world’s leading experts.

Let’s get started. Today’s a very exciting day. I’m having coffee with Dr. Antonio Pellicer. Dr. Pellicer truly needs no introduction. Briefly, he is a professor of Obstetrics and Gynecology at the University of Valencia and he’s also the co-president of IVIRMA. Thank you so much for joining us today.

Dr. Antonio Pellicer:

Thank you, Andres. The coffee is excellent. This American coffee is excellent by the way.

Dr. Andres Reig:

I’m happy you liked it. Tell us a little bit about you first, who Antonio Pellicer is. Where did you grow up? Who were you before you joined the field of reproductive medicine?

Dr. Antonio Pellicer:

Well, this is a long story, so to make it short, I was born in Gandia, which is a small town, 70 kilometers from Valencia. And I basically did all my studies in Valencia. At the University of Valencia and also I did my residency at the University hospital there.

Dr. Antonio Pellicer:

Where I realized, at some point, I should go outside of Spain to improve in the field that I really thought was important in studies and gynecology. Initially, I went to Germany, but I finished up in the United States. And then when I came back to Spain, we created IVI And then now we’re 30 years working at IVI. This is basically how it worked in my particular case.

Dr. Andres Reig:

And that’s amazing, 30 years already.

Dr. Antonio Pellicer:

Yes, 30 years. And in 1990, we created IVI as a project in which we wanted to share the pillars of University education, research, and also excellence in the clinical care of our patients. And in fact, it also became an important business activity, where we had many employees, more than 2,000.

Dr. Antonio Pellicer:

And I could never expect that 30 years later when we were exactly celebrating the 30 years of IVF, we had to stop activity. Everybody went home because of the Coronavirus pandemic. For me, it has been devastating. It has been really devastating. But now we are happy. We are again recovering from there and I’m always pushy and going ahead.

Dr. Andres Reig:

Absolutely. When you started IVI and when you started in the field in general, things obviously were a lot different, both in the field itself and for you. Your role was very different too. What was in the very beginning? What was a regular day like for you?

Dr. Antonio Pellicer:

Well, this may sound like a joke for you, because if you can imagine that at the very beginning I did everything. When I went to the University of Erlangen in Germany, I was working in Germany, because my boss was a strong believer that the Germans were aware of the best, at that time.

Dr. Antonio Pellicer:

So, I went to work at the University of Mainz, but Erlangen, Germany was the first place where they did the first IVF baby. I went to Erlangen to learn the technique. And when I came back to Valencia, I did myself everything. From retrieving the eggs from the patients through upper ascopy, inseminating the eggs, growing the embryos, and then performing the transfer.

Dr. Antonio Pellicer:

After a few months, your mother had joined me. She was a great help for me because then we split the work. She did the lab work and I did the clinics. But it was totally different to what we have today. We actually didn’t understand how important was a series of safety measures and so many things.

Dr. Antonio Pellicer:

We didn’t have the machines that we have today. The only thing that remains more or less the same is the gonadotropins, the stimulating drugs. This is more or less the same, but the rest is totally different.

Dr. Andres Reig:

Yeah.

Dr. Antonio Pellicer:

Totally different.

Dr. Andres Reig:

I can only imagine. Speaking of things that changed since the last 30, 40 years, if you could pick out just maybe four or five key moments, key developments., what are they?

Dr. Antonio Pellicer:

The first key moment is without doubt the use of a transvaginal ultrasound. That was a breakthrough. That was a breakthrough because IVF was developed to treat tuber infertility. So, when we perform laparoscopies to retrieve eggs, many times the eggs didn’t show up. They were involved in additions. We had a couple of complications during laparoscopy, because in order to get into the ovaries to aspirate the follicular contents.

Dr. Antonio Pellicer:

Ultrasound, I think it was the introduction around 1986 it was a big breakthrough. The second one probably was in 1992. There were two. One of them was XY. XY was absolutely relevant because it changed the way we practice today and basically male infertility disappeared. Until the development of XY, we still had a lot of troubles with bad sperm samples.

Dr. Antonio Pellicer:

However, since then, we basically don’t use anymore donor sperm, unless we are treating single women or another type of patient, but not male infertility. So, XY was actually for me the number two. And in parallel, in that year, Alan Handyside published in the United Kingdom the first analysis of the embryos looking at monochromic diseases.

Dr. Antonio Pellicer:

And from there derived the also the analysis of the chromosomal contents and all in all what these two, they call brain plantation genetic testing. I think that this has been also very, very, very important for the development of ENT. And also in general, point number of four, because you asked me for four or five.

Dr. Antonio Pellicer:

Also in general, I think that what we have seen in these 30 years or 40 years is improvements in the lab. There are so many improvements in the IVF lab that in the end have resulted in the embryos of better quality. And this is absolutely relevant and it’s worth mentioning them, because again if you think about it the way we stimulate patients is more or less the same little bit something has changed, but not much.

Dr. Antonio Pellicer:

The embryo transfer techniques have improved using ultrasound, but then we still use the syringe with the catheter as we did in the beginning. It is all about the quality of the embryos that have made the changes and improve the implantation rates that we had 30 years ago. That was about 6% in the best labs in the world to 60, 70%, that those are the best labs in the world have today. So, we have increased 10 times the chances of embryo implantation.

Dr. Andres Reig:

Thinking just to pick one in particular as an example, I like to get your perspective for example on the XY. XY became pretty quickly a widespread thing, that everybody was doing, because like you said, it did, it almost rendered male infertility a thing of the past, pretty much. I’m interested in knowing from your perspective, how did that process happen?

Dr. Andres Reig:

How did you live through the first few papers that were interesting about it until it becoming absolutely commonplace?

Dr. Antonio Pellicer:

Well, XY was in principle an accident. There was a fellow in Brussels doing what is, it was called SuZi. Basically, the technique of improving fertilization with male infertility was to introduce the sperm in between the sonapenisula and the oplasma. He was forbidden to enter into the egg because it was believed at that time that the, you may damage the egg and nothing happens.

Dr. Antonio Pellicer:

That fellow, Gianpiero Palermo, apparently did a mistake and he introduced directly the sperm into the olplasma. And the following day he had pregnancies. He had fertilization and then they had pregnancies. And then they probably the first paper in the landset. For me, it was evident that the technique was important, but since there was an accident in the lab, they didn’t have animal studies.

Dr. Antonio Pellicer:

And it was done directly in human beings. They were very serious people in that department. And they did a serious follow up of children from the very beginning. And published many papers in the nineties about the safety of XI. But yes, it’s true, I mean, this thingy was introduced without previous experimental work, because appeared by chance, by an accident.

Dr. Antonio Pellicer:

So, we learned the technique. We had one of the fellows doing these techniques in Brussels. That summer, we invited him to Valencia and we learned from there, from him, and the results were spectacular. We had a 70% fertilization rate, 80%, and it was amazing.

Dr. Antonio Pellicer:

Then we were the first to be able to biopsy cases of azotemia and freeze and develop a specific technique of freezing of these poor, poor quality sperm and having children. And we probably start with our friend, Manuel. He, unfortunately, passed away a few years ago.

Dr. Antonio Pellicer:

Those years were amazing because we really had a strong line of research in andrology. And we did publish some interesting contributions to delegatory, but the main merit comes from Brussels and from the accidental discovery of XY.

Dr. Andres Reig:

So interesting. So great to hear the inside story of that focal focusing a little more on today. Obviously, the field in terms of what we can do, but also in its actual size of people has grown exponentially. And then the people involved has grown a lot.

Dr. Andres Reig:

We just had, a couple of weeks ago, virtual ASM Congress and it was great. There was a lot of information, but we obviously all missed seeing each other in person and then celebrating the actual meeting itself.

Dr. Andres Reig:

I can’t help but feel like the old school people, so to speak, all you all know each other, it’s a big community. And, you know, everybody always says, it’s a very small world. As the bad world is growing and expanding, it’s definitely become a lot less personal and a little more diffused.

Dr. Andres Reig:

How important do you think to you is the familiarity with each other, that idea that we’re all friends working towards the common goal rather than these different competing groups within reproductive medicine?

Dr. Antonio Pellicer:

Well, as you say, in the beginning, I remember when we started in Spain, we were three or four groups. People used to meet to, to change experience. I also enjoyed very much to go to the meeting that Davey Meldrum is organizing every single year, except 2020 in California. First in Santa Barbara, now in San Diego.

Dr. Antonio Pellicer:

At that meeting, I enjoyed going, because there were many groups including his own group, but also it was Richard Scott when we were not together and it was also Bill Schoolcraft and others. And I enjoy very much sitting with them and exchanging our experiences and speaking honestly about what works and what it doesn’t work.

Dr. Antonio Pellicer:

Today we have many publications, there are many scientific publications devoted to infertility. And I have had the honor to serve as co-editor in chief of Fertility and Sterility for almost 10 years. Our term finishes next July. And so I have had the opportunity to be in the first line of all the developments.

Dr. Antonio Pellicer:

I think that today the world is moving through what comes in the scientific literature, but it comes so much, that if you don’t use the social networks and the social media, that may help to spread the news that appears, is difficult to get all this information.

Dr. Antonio Pellicer:

Although today, as you said and mentioned that this is nice to see your old friends and meet with them and have meetings, in reality, people are always checking their iPhone to find out whether something new comes up every day.

Dr. Andres Reig:

Fair enough. That’s true. It’s grown a lot, but we’re definitely a lot more connected than we were before.

Dr. Antonio Pellicer:

Exactly.

Dr. Andres Reig:

That’s fair. I want to ask you a similar question, but looking forward to what I asked you before about the three or four key things that have happened in the past, what do you think are going to be the two or three biggest breakthroughs or at least the biggest areas in which these breakthroughs are going to occur in the next 20, 30 years moving forward?

Dr. Antonio Pellicer:

Well, according to my understanding, I may be wrong, but this is the way I think, I still believe that, any of them is all about the embryo and very few about the endometrium. I always said that a good embryo implants anywhere. And as an US resident, I’m sure you have assisted in the emergency room with abdominal pregnancies.

Dr. Antonio Pellicer:

Even women who had no uterus. Good embryo implants anywhere. And again our colleague, Bob Peltier presented last year at the AH meeting, how if you have three euploid embryos, you reach 93% delivery rates. But you need three euploid embryos. With one embryo you arrive at 65, 67%.

Dr. Antonio Pellicer:

What is missing here is still ways to evaluate the embryo. So, PGD or pre-implantation genetic screening or testing is not enough. And I think that we need other methods that together with PGT may provide a better selection process and may be using algorithms developed with the time-lapse machines.

Dr. Antonio Pellicer:

I don’t know. But I think that there is a way to go into the lab. The second point became apparent, then evident after the pandemic, but we are working on it for some years. In fact, I tried 15 years ago and it didn’t work, because I didn’t find the right people to join, because I needed engineers to self-monitor that cycle.

Dr. Antonio Pellicer:

We are asking our patients to come to our offices almost every day or at least almost every two days. And because the pandemic became evident, but we are working with a segment of the population that works and that they need the time for other things. So, if we are able to change the way that we practice ART and patients can get monitored at home or from the office, everything will change.

Dr. Antonio Pellicer:

And also the facilities you need for IVF, because you will invest less money in opening an ART clinic because you just need a space for pickups and also for recovery, but no more than that. I think this is going to change a lot. They are developing interesting tools to accomplish that.

Dr. Antonio Pellicer:

And then what the future will bring probably also the lab will become more automatic. Why? Because the results are very hand-dependent because they are related to the ability to do a good sperm injection, the ability to do a good embryo biopsy, the quality of their culture systems.

Dr. Antonio Pellicer:

It’s manual like how cars were manufactured 200 years ago and today the process is totally automatic. I think one day will arrive that IVF will be done in a more automatic way.

Dr. Andres Reig:

That’d be interesting. I’m very surprised you didn’t mention as one of the things the whole concept of genomic editing and all of these, which seems to be in everybody’s mouth nowadays.

Dr. Antonio Pellicer:

Well, the thing is that, that needs some more time. I don’t know if you mentioned that, how I see the future in 10 days or in 10 years or 20 years. I read the, just this morning paper in the cell. nI using the CRISPR technique, how they have managed to remove an extra chromosome.

Dr. Antonio Pellicer:

But this has many questions still to be answered.

Dr. Andres Reig:

Of course.

Dr. Antonio Pellicer:

It will be another important field to work in. Obviously is not my field of specialization, but what I understand from people who are basic embryologist and basic biologist is that, it is possible, but it’s not easy. And maybe it’s not feasible.

Dr. Andres Reig:

Thank you. That’s all we have time for, unfortunately, but it’s been amazing to talk to you. Thank you so, so much for being with us today.

Dr. Antonio Pellicer:

Thank you, Andres.

Dr. Andres Reig:

Will you be back?

Dr. Antonio Pellicer:

Oh. Of course.

Dr. Andres Reig:

This has been another episode of FertiliPod by IVIRMA. Thank you so much for listening. Tune in next week for more research and topic discussions in all things reproductive medicine. See you next week.


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