Is There a Preferred Protocol for ART?

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Hugo Verhoeven, MD: “Good morning, my name is Hugo Verhoeven from Dsseldorf, the Centre for Reproductive Medicine, and I’m on the Editorial Board of OBGYN.net. I’m reporting from the fourth meeting of COGI, Controversies in Obstetrics and Gynaecology, in Berlin, Germany. It’s an exceptional honour for me to talk to Dr. Antonio Pellicer, from Instituto Valenciano de Infertilidad, in Valencia in Spain, who is one of the leading IVF or ART people in Europe, and certainly also in the complete world.

We are going to discuss with each other a very hot topic: the treatment of the older patients. We have a growing amount of patients coming to see us at an older age, so not like some years ago where the mean patient was 25 or 30 years old. We have more and more older patients and of course the pregnancy rate in those patients is lower. We should discuss now what the possibilities are? What are you doing? So, first of all, why do you think that so many older patients are coming to see us?”

Professor Antonio Pellicer, MD: “Well, I think there are locational and professional changes in our society that have contributed to this tremendous change in the age of the patients who come to us, and definitely there has been a social change in our work.”

Hugo Verhoeven, MD: “Is that only because women are more active in their professional lives, or is it because the patient decides to enjoy their life longer and to say: okay, children are coming into our lives, it will change tremendously, so let’s wait for that until a later stage?”

Professor Antonio Pellicer, MD: “Probably both, but I would say that the most important parameter would be the fact that they are busy with their work and they want to reach their goals, as men do, and that delays the desire of child-bearing a few years. And, as we know, the possibility to be regularly fertile starts to drop after the age of 37 and drops dramatically after the age of 40.”

Hugo Verhoeven, MD: “The problems we have as infertility people to treat our older patients is a problem that we have known for many, many, many years. It is more difficult for an older woman to get pregnant. So, what can we offer those patients now as alternatives to the routine IVF ovulation induction that we are using? What can we do especially for older people to get pregnant?”

Professor Antonio Pellicer, MD: “I think the clue is the introduction of pre-implantations and I think diagnosis or screening in the IVF tools. In other words, until now, we were able to produce or to create a human embryo in the lab and transfer them without knowing whether these embryos were normal or abnormal.

We have learned that up to 70% of the embryos produced by older patients are abnormal, they carry aneuploidy risks, mainly Downs Syndrome, Turners Syndrome, and other aneuploidy risks, which are defects of embryos, which are unable to implant. That means that the woman will never become pregnant or that she will become pregnant but obviously will have a child with defects.

So I think that this has been a major achievement because now we know that only 30% of those embryos are normal so in our place, we always recommend patients to screen the embryos before they are transferred because of these numbers that I have provided to you.”

Hugo Verhoeven, MD: “But I think there are two problems with that: PGD is expensive, and number two: to select something, you need a certain amount of embryos and older people have problems of producing eggs.”

Professor Antonio Pellicer, MD: “Correct.”

Hugo Verhoeven, MD: “Follicles, oocyte, embryos at all. What can we do?”

Professor Antonio Pellicer, MD: “Correct. You are totally right. PGD is expensive, this is true, but again this is an additional tool that gives you information and perhaps avoids repeated IVF attempts. So at the end of the day, either you get pregnant or you get sufficient information to stop, say, this way and go to another way that we will discuss later on.

Concerning the fact that up to 70% of these patients will be low responders and they will not provide a sufficient number of oocytes and embryos to perform this kind of diagnosis, this is completely true. I mean I am talking about one possibility that unfortunately can be applied only in 30% of this population.”

Hugo Verhoeven, MD: “So if you are stimulating the patients, you have a certain amount of embryos, and if you have not got many embryos, you just get them back and you say, okay, let’s see what’s going to happen.”

Professor Antonio Pellicer, MD: “Exactly, and then you finish up with less implantation and less pregnancy rates and more miscarriages.”

Hugo Verhoeven, MD: “Exactly. If you have a lot of embryos, you can do a PGD of them?”

Professor Antonio Pellicer, MD: “Yes.”

Hugo Verhoeven, MD: “So there is another alternative: patients who are having PGD and still are not going to be pregnant or patients who have not got enough embryos, for those we have the alternative of the oocyte donation. You are one of the leading people in this specialty. What about ovum donation?”

Professor Antonio Pellicer, MD: “Ovum donation? Well, first of all, in Spain, ovum donation has several advantages. It is regulated by law and this is very important for the patients. Secondly, it’s anonymous, which is very important for most of the patients, although some come with their own donors, being a sister or relative. But this is forbidden, it has to be anonymous, and, I believe this is an advantage, donors have to be between 18 and 35 years of age, and they are screened for every single hereditary or genetic disease, including karyotyping and, of course, sexually-transmitted diseases and hepatitis, etcetera, and more importantly, HIV.

Once we have that, we create a list of potential recipients in the computer and we are working with many foreign patients, not only from Spain – up to 20% of our patients are from outside Spain. What we do is we freeze the sperm of the partner and our patients are in advanced oestrogen replacement therapy so they, our patients, no matter whether they live in Valencia or in Hamburg, they are taking pills and once we have a donor who fits their physical requirements, meaning the colour of the eyes, the hair, blood group, etcetera, we call our potential recipient in Hamburg, saying that we are going to inseminate your oocyte.

We inseminate the oocyte and they have three to five days to come to us, they get the embryo replacement and they go back home. Ovum donation, once it’s accepted, because the problem is to accept a third partner in the couple, but once you accept the third one, it’s a very successful system because we are talking about implantation rates today of 32-35%, so it’s a successful technique.”

Hugo Verhoeven, MD: “I was very surprised to see your success rates, so what’s your secret?”

Professor Antonio Pellicer, MD: “I think there is no secret. First of all our system does not synchronise a donor and a recipient from the beginning of the cycle because that can end up with a bad cycle for the donor. So in the middle of this stimulation, we check whether the whole stimulation goes well and then we select the donor and the recipient, and we can do that because our recipient is already taking oestrogen and we have the sperm in the clinic. So this is the first thing: that we usually get good oocytes to our patients.

The second thing is that, in general, not just in our place but in all the places, also yours, the laboratory conditions have changed and have improved very much in the last few years so now we have better embryos. And I think, thirdly, the fact that this is an artificial cycle, without ovarian stimulation and without ovum pickup with needles and anaesthesia and other things that are definitely stressful for the woman, that it makes the difference.”

Hugo Verhoeven, MD: “But don’t you think that the trick is, or the secret is to have good donors?”

Professor Antonio Pellicer, MD: “Ah, definitely, definitely. I have shown also today in my presentation the age of our donors. The mean age is 25, and I think this is the best thing to start, and also, if you have bad oocytes, to be honest enough to stop the cycle and look for another donor for this patient and not give to the patient whatever is in the lab. I think that is important.”

Hugo Verhoeven, MD: “You make it very easy for our listeners. If patients want to have oocyte donation, egg donation, in Spain, they come to see you. You talk to them and sperm is frozen.”

Professor Antonio Pellicer, MD: “Correct.”

Hugo Verhoeven, MD: “Then the local doctors, wherever in the world, are starting the preparation of the endometrium so that the endometrium is ready at the moment that your eggs are ready.”

Professor Antonio Pellicer, MD: “Exactly.”

Hugo Verhoeven, MD: “The eggs are fertilized with the sperm that is frozen.”

Professor Antonio Pellicer, MD: “That’s how you do it.”

Hugo Verhoeven, MD: “The patient comes over only once for the embryo transfer.”

Professor Antonio Pellicer, MD: “Only once. Correct.”

Hugo Verhoeven, MD: “And then goes back to their own country.”

Professor Antonio Pellicer, MD: “That’s totally correct.”

Hugo Verhoeven, MD: “Is it a possible question to ask how much it costs in Spain to do oocyte donation?”

Professor Antonio Pellicer, MD: “I think it’s about 5,000 Euros all together, more or less. It depends if they need ICSI or they do not need ICSI. Some patients require also PGD.”

Hugo Verhoeven, MD: “Exactly.”

Professor Antonio Pellicer, MD: “I have some figures that show that the donors also have abnormalities, but in general, people do not need the PGD; however, there are people who are very concerned about the possibility to have an abortion while they are pregnant and this is how PGD has been accepted and requested in many circumstances.

Even if you don’t talk about PGD with them, but they ask for it because they have learned in the information that we provide on the internet, from television, etcetera, that there is a technique that is able to screen the embryos before you get pregnant, so you don’t have to deal with the discussion whether you will miscarry or have an abortion or not.”

Hugo Verhoeven, MD: “Well, I think this was very informative for all of us. I thank you very much, Dr Pellicer. It was a real pleasure. Thank you for being here.”

Professor Antonio Pellicer, MD: “Thank you.”