How to Prevent Multiple Pregnancies

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Hugo C. Verhoeven, MD: "Good morning, my name is Hugo Verhoeven and I'm from the Center for Reproductive Medicine in Dusseldorf, Germany. I'm on the Editorial Board for OBGYN.net, and I'm reporting from the meeting of the American Society for Reproductive Medicine in Orlando, Florida. I have the great honor to talk once again with Dr. Juergen Eisermann from the South Florida Institute for Reproductive Medicine. Juergen, we've known each other for many, many years and once again we're going to talk with each other in English. You are German, I'm Belgian, I'm working now in Germany, and you've been working now for thirteen years in private practice in Florida. I would like to have a small conversation with you on the topic of multiple pregnancies and the ways to prevent high order multiple pregnancy. This is especially in Europe very controversial and as you know there are countries like Scandinavia where only single transfer is allowed. Giving back three embryos is forbidden, and if this resulted in a multiple pregnancy, you're in trouble. But there are some possibilities to reduce the probability of producing high order multiple pregnancies, tell us about what you are doing. First you should tell our readers where you're working and what you're doing exactly."

Juergen Eisermann, MD: "Sure, I'm somewhat in a unique situation, I grew up in Germany, I did my medical school in Munich, and started out my residency at the University of Munich only to run into my future wife who was a medical student in Munich as well but she's an American citizen. We both decided after we finished medical school we would give it a shot here in the states. She's a pediatric allergist and immunologist in private practice, and we've both been living in Miami for the last thirteen years. We always say it's a hot place but somebody's got to do it. We're in a different society now; I experienced Germany as a society in which a lot of the healthcare issues were covered. Health insurance is a common state regulated and guaranteed benefit to everybody that lives in Germany, and I'm sure that applies to the majority of the European countries. However, here in the United States health insurance in general is still somewhat of a privilege. It is not a guaranteed package deal for your everyday employee, mainly in smaller businesses, and what insurance will cover is totally different here in the states than in Germany which brings me to the point that I wanted to make. I had to adjust to this particular change here and it actually hits home when it comes down to how do you regulate in vitro fertilization and how do you issue the rules and regulations in terms of preventing high order multiples. We all know that high order multiples have skyrocketed over the last few years, and it's because of the fertility programs here in the states. They have significant problems to both the mother as well as the fetus and definitely are a less than desirable situation. At the same time, when a couple has to shell out their own dollars for a procedure they want to have a benefit to cost ratio that is favorable which puts us in a tough spot because we may be giving the opportunity to act unethically knowing what kind of problems multiple pregnancies can have. At the same time, we're feeling a certain responsibility towards the couple saying that we want to give you the best chance for pregnancy and that's a significant dilemma that everyone of us here has to deal with. You already have the rules set for yourself - you already know the government says we can't do this so you're not in any kind of dilemma. We, however, here in the states are in a significant dilemma and we also recognize the medical benefits of reducing the risk for multiple pregnancies. Don't underestimate that, I think this has been the American Society for Reproductive Medicine's main issue over the last year or two. I know that this meeting in particular is going to focus on that, in fact, we are presenting our data in an abstract on Wednesday about how we are going about trying to reduce high order multiples."

Hugo C. Verhoeven, MD: "So what are you doing?"

Juergen Eisermann, MD: "Without compromising the patient's outcome, we have started working with the extended embryo culture, the so-called blastocyst culture system, in a major way. I think this particular approach was our saving grace because we are now able on over 60% of our patients to offer a day five embryo transfer with the kind of embryos that are having 30% or close to 35% implantation rates where I now can offer a realistic chance for pregnancy."

Hugo C. Verhoeven, MD: "Let us repeat that - a blastocyst that has an implantation rate of 35%."

Juergen Eisermann, MD: "Certainly Grade I to Grade II blastocysts have that kind of potential which is almost double the potential that an eight-cell embryo has, and we are maintaining pregnancy rates that are in the high 50's with ongoing pregnancies in the high 40%. Now that's an acceptable situation. What we've been actively doing with this is reducing our triplet rate from about 10% to less than 2%, and that's what we feel is a viable compromise between optimizing the patient's return on investment and reducing the risk of a potential problem later on."

Hugo C. Verhoeven, MD: "What is the percentage of the eight-cell embryos that reach the blastocyst stage? I realize that the laboratory quality must be excellent for working with blastocysts, so in your laboratory, what is the percentage of embryos that reach the blastocyst stage?"

Juergen Eisermann, MD: "I would say for every four eight-cell embryos that we have that are Grade I or II, we can expect between two and three blastocysts. What we're thinking about doing right now is actually focusing more on freezing eight-cell embryos and just advancing three of the eight-cells that we have that look best in quality to the blastocyst stage so that our actual cancellation rate - meaning having no embryo transferred at all - is negligible with this approach. However, we have of course certain patients, mainly 35 and older population, that we still experience some problems with in terms of caring them to the blastocyst stage. The dilemma we're facing here is - shall we take a chance not transferring any embryos if the blastocyst culture should fail versus transferring some eight-cells that may have a better chance of making it in vivo within the uterus than keeping them in the incubator with us. We're working on that with trying to work on different media culture systems and so forth."

Hugo C. Verhoeven, MD: "But I think that's a very good point. Let's compare this with our situation in Germany. We are not allowed to freeze embryos, only pronuclei, so we have the problem that if we bring three pronuclei into culture that after day two or day three we have only two eight-cell stage. If we wait any longer, the risk that we are not going to be able to transfer a blastocyst is very high and that is the reason why especially in Europe, in Germany and also Switzerland, the tendency is to go away again from the blastocyst transfer because the cancellation rate of transfer is much too high. So that's a very good point that if you freeze at an eight-cell stage, then at least the probability you are going to have at least one, two, or maybe three blastocysts is quite high. Would you really do a transfer of three good blastocysts?"

Juergen Eisermann, MD: "Never, we have seen at this point in time that the only way we can maintain a very low triplet pregnancy rate is by limiting the transfer to two blastocysts. The dilemma we're still having is that freezing blastocysts and thawing them for future transfer has its difficulties."

Hugo C. Verhoeven, MD: "Yes, exactly."

Juergen Eisermann, MD: "Vitrification seems to be a partial answer but we've also come to learn that after the thawing process non-fully expanded blastocysts still have a pretty decent potential for pregnancy. But one of the dilemmas we're facing in our practice is that while we can get very good overall pregnancy rates with frozen embryo transfers, we're somewhere in the 50% range, we have a very high pregnancy loss and the term pregnancy rate is only somewhere around 26%-27% so we lose almost half of our frozen embryo transferred derived pregnancies. We're still not clear as to why and how but we're working on that very hard. My personal feeling is that if you want to go down, for example, to a single embryo transfer, you have to offer a very good freezing program and a very realistic chance for frozen embryo transferred pregnancies in order to convince the patient to do it."

Hugo C. Verhoeven, MD: "But you have no other choice - if you have three blastocysts, you need to give them back or you need to freeze them - one or two. You're not going to throw them away."

Juergen Eisermann, MD: "No, under no circumstances."

Hugo C. Verhoeven, MD: "So to finish our conversation, what is your overall pregnancy rate of your center?"

Juergen Eisermann, MD: "We have a ongoing pregnancy rate of about 48% this year and that includes everything across the board - IVF, ICSI, and egg donation. The egg donation program enjoys the highest pregnancy rate, obviously, it makes out about 20% of our overall IVF volume but we've been able to offer our patients that have to resort to egg donation about a 72%-73% pregnancy rate with a triplet rate in that particular subgroup of patients still being about 8%. That again is derived from the fact that if you are spending the amount of money that it takes to do egg donation, your desire to be successful and your willingness to be aggressive is relatively high. The dilemma is those are the older women that are already lending themselves more towards obstetric complications than the potential for maternal complication so we're still working on that very hard. I think within the next couple of years we'll see that even single blastocyst transfers will have a very acceptable pregnancy rate, and I hope we get that frozen transfer program organized to a point where we can be happy with it."

Hugo C. Verhoeven, MD: "Your pregnancy rate is high; what about your baby-take-home rate? That's what interests our readers."

Juergen Eisermann, MD: "This is what I'm talking about, ongoing to take-home-babies is in the high 40's."

Hugo C. Verhoeven, MD: "In the high 40's, well, I need to finish this conversation by congratulating you. We can only dream in Europe about that high pregnancy rates, our regulations are that severe that nobody can reach that figure."

Juergen Eisermann, MD: "You can dream about these pregnancy rates; what we can do is dream about insurance covering ours."

Hugo C. Verhoeven, MD: "Juergen, thank you."

Juergen Eisermann, MD: "It was a pleasure likewise."