Iatrogenic Multiple Pregnancy

From American Association of Gynecological LaparoscopistsOrlando, Florida, November 2000

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Dr. Hugo Verhoeven:  “I’m Hugo Verhoeven from the Center of Reproductive Medicine in Dusseldorf, Germany, and I am on the Editorial Board of OBGYN.net.  I’m actually in London, and yesterday evening at the Royal Society of Medicine a unique new book called ‘Iatrogenic Multiple Pregnancy’ was introduced to the international press at an event organized by the Parthenon Publishing group. It is my exceptional honor to talk with the two editors of this unique book, Dr. Isaac Blickstein from Rehovot, in Israel and Dr. Louis Keith from the Center for the Study of Multiple Births at Northwestern University in Chicago.  Gentlemen, good morning, writing a book on iatrogenic multiple pregnancies leads to my first question, exactly what are iatrogenic multiple pregnancies?”

Dr. Isaac Blickstein:  “Good morning, Hugo.  Thank you for your efforts to promote our book and its message.  The epidemic of multiple pregnancy is seen and witnessed all over the world mainly in developed countries but also now in developing countries.  Latrogenic comes from the Greek word iatros which means physician, so it is a physician made multiple pregnancy.”  Although multiple pregnancies are also spontaneously conceived, the term refers to those conceived by physician intervention. These iatrogenic pregnancies are contributing to the mortality and morbidity of babies all over the world.

Dr. Hugo Verhoeven:  “Before we talk about the content of this book, I would like to know some more of the reasons why we have a worldwide explosion on multiples and especially high-order multiple pregnancies.  Louis Keith, could you give us some information on that?”

Dr. Louis Keith:  “Good morning, Hugo, the answer is really quite simple.  As you and the readers of OBGYN.net know, the use of agents to induce fertility has literally exploded since 1985.  These drugs came on the market in the mid 1970’s but they were in the hands of very few and highly trained specialists by the mid 1980’s, after the exceptional breakthroughs of IVF, it became apparent that generalists and people with some but not specialist training could also prescribe these drugs.  One of the issues here is the use of ovulation induction agents and what happens after it.  If people think that the epidemic is due to IVF alone, they are incorrect.  In reality, the epidemic is primarily due to the use of ovulation inducing drugs, and these drugs are available either in the brand name or in a generic name all over the world.” 

Dr. Hugo Verhoeven:  “It is my impression that there is not enough exchange of information between the different subgroups of doctors producing multiple pregnancies and taking care of those pregnancies.  It is my impression, being in reproductive endocrinology, that we are not convinced about the fact that we are producing real problems for the obstetricians.  Why don’t we have better cooperation between reproductive endocrinologists, obstetricians, neonatologists, and pediatricians?” 

Dr. Louis Keith:  “First of all, everybody sees the problem from their own point of view.  The reproductive endocrinologist has as a goal to make the woman pregnant.  That’s all he or she has to do.  The obstetrician has to carry the pregnancy to as great a length of gestation as is possible.  The pediatricians have to deal with the babies that are subsequently born and handed over to them.  They all represent steps in a chain but even if and when these groups do talk, neither can enter into the turf of the other and change its practice pattern.”

Dr. Hugo Verhoeven:  “I think an important question is why are the reproductive endocrinologists producing that many high-order multiple pregnancies?  The reason could be quite apparent; the procedure of ovulation induction and in vitro fertilization is a highly costly procedure in terms of money, time, and emotional investment.  Therefore, the centers do everything to optimize their success rates and they believe that giving back as many embryos as possible will increase their pregnancy rate, which has been proven wrong.  Your comments please, Isaac.”

Dr. Isaac Blickstein:  “I think, Hugo, that you put it perfectly.  Part of the reason is that people are coming to that treatment is to get a baby.  However, at the stage of treatment sometimes they are not informed about the risks that a high-order multiple pregnancy may result from the treatment.  For example, if a couple has been trying to have a baby for more than say five, seven, eight, or ten years - this is their goal in their life.  They come in for treatment and the physician will ask them that since there is a chance that they will have a triplet pregnancy, would they agree to continue?  Most of them will urge the physician to do it because they are not aware of the implications of this.  You were 100% correct in pointing out the dissociation between those who are giving fertility drugs, those who are providing artificial or assisted reproduction, those taking care of the pregnancies, and those that take care of the babies.  In addition, there is a dissociation between what is happening to those babies in the future.”

Dr. Hugo Verhoeven:  “That is exactly my next point, what’s wrong with producing multiple pregnancies or high-order multiple pregnancies?  What is the problem - why are we against that?”

Dr. Louis Keith:  “I think it’s very simple, Hugo.  These are all high-risk pregnancies and the risk falls to the mother and the risk falls to the infants.  In terms of the mother, there is a much higher incidence of certain life threatening conditions such as preeclampsia and eclampsia, such as post-partum hemorrhage and anemia. The risks to the infant are particularly devastating.  There are two problems - low birth weight and preterm delivery.  In terms of comparing triplets, for example, with singletons, the risk of being born with low birth weight and preterm is probably ten times the risk of that of singletons.  Now that translates into the fact that about 90% of these babies will wind up in the NICU, many of them with RDS, many of them with bronchopulmonary dysplasia, and many of them with bills going into the hundreds of thousands of dollars.  All of this would be fine if the mother ultimately took home neurologically intact children but the incidence of cerebral palsy is also markedly advanced over that of singletons or twins.”

Dr. Hugo Verhoeven:  “I think it is important to go back to the financial aspects of high-order multiple pregnancies.  In many countries around the world ovulation induction, insurance companies do not pay for in-vitro fertilization, and ICSI.  So the patients have to invest a lot of money for their treatment but as soon as pregnancy is achieved the costs for taking care of those pregnancies and the children is paid for by the national security.  This circumstance means that we are producing a huge cost factor for the community at large.  Do you have any idea what it would cost to take care of triplets until they are adults?  What would that cost the community?”

Dr. Isaac Blickstein:  “I cannot tell you exactly because the bills are paid differently all over the world.  For example, in Israel the reproduction phase of the iatrogenic multiple pregnancies have no costs because the government pays for the patients to get pregnant.  The patient only pays for raising those children.  However, this doesn’t mean that society does not pay for that also.  Given the fact that ovulation induction or IVF is the same price for having one child, two children, or more, the factor of multiplying the cost does not occur during the reproduction phase. Nor is it in the pregnancy caring phase.  It is only afterwards when those babies are delivered.  You don’t need to be a mathematician to do the calculations.  For example, suppose an infant stays one day in the NICU, it costs $2,000 if you have one child - one day is $2,000.  If you have a pregnancy ending with two children, one day is $4,000.  If you have three children, it’s $6,000 per day and I’m speaking about minimal costs.  Some of those pregnancies end up with two months at the NICU.  The average in the United States, for example, is about 40-70 days in the NICU for triplets.  I’m not speaking just about cash money; The load surrounding those families is an enormous economic project, not to mention that people have no time for themselves, or that there are some serious effects on the family structure following such costly deliveries.”

Dr. Hugo Verhoeven:  “Louis.”

Dr. Louis Keith:  “Isaac has generally answered your question but within our book we have a chapter called ‘Economic Considerations’ by Hall and Callahan.  These were the two authors who put out the first article on the cost of multiples that was published in the New England Journal of Medicine, and I will quote just a few words that amplify what Isaac has already said.  ‘Admittedly these costs have not been well quantified, but they include the potential need for surgery, specialized healthcare providers, surveillance for sight and hearing abnormalities, and physical therapies for treatments related to developmental delay, learning difficulties, decreased motor skills, and speech and language difficulties.  Monthly costs for very low birth weight infants are estimated to be 3-60 times those of the average child during the first three years of life.  More over, these studies have indicated that the direct medical costs in the first year of life average $10,139 for very low birth weight infants compared to $179 for control term infants.’”

Dr. Hugo Verhoeven:  “During the time that we have been conducting this interview, we were joined by Donald Keith, the twin brother of Louis and he has some remarks.”

Dr. Donald Keith:  “There’s a new term that we’re using now in the U.S. Department of Defense and it’s called ‘residual unmitigated financial risks.’  What you’re saying here is that when you start this pregnancy you’re building an unresolved and unknown financial risk pool that can vary with couples so if one situation is worse, their risk pool is higher.  Another who has a normal delivery has no risk pool but when you start you have no prior knowledge, and you can’t make a mitigation plan.”

Dr. Hugo Verhoeven:  “Let’s go back to the book now.  Isaac, what was the idea behind this book?  When did you decide to collaborate in writing a specialized book like this?”

Dr. Isaac Blickstein:  “The problem of iatrogenic multiples has bothered the medical profession for many years.  The epidemic started many years ago, but it was not until 1997 when Louis and I visited your clinic in Dusseldorf to see its wonderful results. On the way from the FIGO Copenhagen Conference to Dusseldorf, we started to outline the book.  We had in mind to write for all professionals, not only for the fertility experts, pediatricians, and obstetricians but also for all sorts of professionals that deal with that problem and this was the first step.  We were fortunate that David Bloomer of the Parthenon Publishing group accepted our ideas immediately, and with the help of good friends like you, Hugo, we started this project in 1997.  The initial idea was to have an edited book but in such a fast growing subset of medical literature, yesterday’s news had no relevance to today’s literature.  We had to update this book constantly.  To do that efficiently until the last moment of the production phase, we invented this idea of editorial inserts.  We’ve put a lot of inserts into the book – updating, giving other views, and discussing points that were not discussed by the respective authors in order to give the reader a really up-to-date text of the literature.  In addition, we have been fortunate to have the contribution of a unique artist who is a medical doctor, and I would suppose that Louis can introduce this concept of David Teplica better than me, thank you.”

Dr. Hugo Verhoeven:  “Louis.”

Dr. Louis Keith:  “Before that, I’ll comment on the book’s style.  There are twenty chapters and approximately sixty inserts.  The inserts are quite specific and readable in their own; each one is numbered, titled, and referenced.  One of the real qualities of the book is that it’s so well referenced and every reference is as up-to-date as we can make it.  David Teplica is a plastic surgeon and has a Master of Fine Arts from the Art Institute of Chicago.  It was he who provided the aesthetics of the book.  The cover of the book sets the tone for the pictures and the graphic illustrations that follow.  It shows a pair of identical twins at the age of one hour when they were put next to each other in the same crib.  One of the twins immediately began to suck the nose of the other twin.  This is a striking photograph and is probably unique in the literature of books that are directed toward physicians.  The same twins, in another pose taken later in that same photographic session, were used on the cover of a book, which was a national worldwide bestseller.  David then continued this photographic essay with twenty additional photographs of adult twins, of children who are twins, and even a couple of mothers who were pregnant with twins in poses with their husbands.  He also has a self-portrait with his large hands showing the tiny feet of his infant nephew.  Altogether it is a most remarkable photographic complement of a unique text.”

Dr. Hugo Verhoeven:  “I note twenty-one topics, each of them were written by an authority.  Isaac, could you maybe give a short overview of the topics discussed in the book?”

Dr. Isaac Blickstein:  “We tried to cover all aspects of this important issue.  We started with a spectrum of iatrogenic multiple pregnancy and then we listed all the problems.  First, we detailed the natural history of twins, the problem of monozygotic twinning in high-order multiples and iatrogenic multiples, and then we went over how to avoid those multiple pregnancies in ovulation induction and reproductive technologies.  We listed the maternal complication and prophylactic measures against pre-term delivery.  Then we discussed the early recognition of iatrogenic multiple pregnancy by ultrasound and obstetrical consideration of premium iatrogenic multiple pregnancy.  Regrettably, we also had to discuss selective termination of malformed fetuses and multiple fetal pregnancy reduction, which is considered by many as the ultimate paradox of fertility treatment.  Finally, we discussed the genetic aspects of multiple pregnancy, compared reduced versus non-reduced multiples, and then proceeded to the final stage of the book with the economic evaluation of the problem, long term health, psychological outcome, education of the parents, the transition to parenthood, and some aspects of the religious attitude toward the problem from the Jewish, Moslem, and Christian point of view.  Ethical and legal implications were discussed at the end, and we added an appendix with a list of help associations all over the world that may provide the parents with a consultation and with immediate help for raising those multiple pregnancies.”

Dr. Hugo Verhoeven:  “Louis, what for you is the highlight of the book?”

Dr. Louis Keith:  “For me, the highlight of the book is the fact that we brought together a number of absolutely disparate opinions on a problem that is really urgently in need of attention.  This is a classic instance of an elephant being examined not by two or three blind men but by dozens of blind men working separately.  The practitioner in the real world has little opportunity to get the opinion, let us say, of the person who does the reduction, person who makes the babies,  person who does its genetic evaluations, or educates parents.  This book does it all.  I’m pleased that we were able to give such a broad discussion to the topic so that it will be a value to practicing physicians.”

Dr. Hugo Verhoeven:  “Donald, some further remarks?”

Dr. Donald Keith:  “I’m speaking as a professional twin now, we’re talking about this book encapsulating definitions of success.  The fertility specialist cries success when he implants the ovum, now if there are five he is even happier.  He hands the pregnancy to the obstetrician who regards him with blazing eyes and asks - now what have I got to do?  The obstetrician’s definition of success is five live children.   The neonatologist looks at this little group and says - oh my goodness, what am I going to do?  Well, months later they’re all out of the hospital and he also can claim success.  But the parents are faced with multiple birth children with many disorders in many cases, and who pays the bill?  The ultimate success or failure is the taxpayer who has to mitigate the unresolved risk, and the taxpayer is not going to say this attempt to resolve infertility was a success.”

Dr. Hugo Verhoeven:  “Donald, what is your opinion of this book?”

Dr. Donald Keith:  “This book is extremely important because it points out the pitfalls of high-order multiple birth and it points it out in a crisp, clear way.  The inserts allow somebody who is in trouble to quickly get some up-to-date information and go on to do what they have to do.  It’s written so that it’s easily read, easily understood, and one doesn’t have to ponder over the words in here.  They’re crisp, clear, pointed, and direct.”

Dr. Hugo Verhoeven:  “Is the book available right now?”

Dr. Louis Keith:  “Yes, the book is available, Hugo.  On OBGYN.net at some point there will be a banner from the Parthenon Publishing Company, which will allow your readers to get in touch with them and purchase the book.  I will simply say that the Parthenon Publishing group has offices in London and New York.  A further reference for your readers is the ISBN number, which can be used at any bookseller - ISBN 185070-726-X and it has a copyright of 2001 with the Parthenon Publishing group.”

Dr. Hugo Verhoeven

:  “Gentlemen, thank you very much for this very interesting interview.”