Louis Keith, MD

n little more than two decades, the subject of multiple pregnancy has evolved 	from an obstetric curiosity to an issue of international medical and social concern. The overall number of multiple 	pregnancies has increased dramatically, not only for twins, but also for triplets and higher-order births. In addition, 	physicians and society are now concerned with a previously unknown type of multiple birth--the iatrogenic multiple 	pregnancy (IMP).

 Many new forms of assisted reproductive technology (ART) are 	now available to help infertile couples achieve a pregnancy. Clearly, IMP is not a desired outcome of ART and must, 	instead, be considered a complication of ART.

Concerns regarding IMP relate primarily to three issues. First, the possibility of truly higher-order multiples 	(three to nine fetuses) is clinically real. Second, multiples, particularly those of higher orders, mirror and 	magnify what are generally acknowledged as two of the major obstetric concerns worldwide: low birth weight and 	preterm delivery. And third, the risk of pregnancy loss following multifetal reduction (MFR) is real and substantial. 	The benefits of MFR are most obvious in women with higher-order pregnancies (four or more fetuses); without reduction, 	prematurity is a certainty. Overall, only about 40% to 45% of pregnancies undergoing MFR are delivered at term.

 Issues such as these form the basis of an emerging international debate on the ethics of 	creating multiple pregnancies and the subsequent need for facilities to care for large numbers of preterm infants.

 Traditional statements about expected numbers of multiple pregnancies 	have undergone considerable revision in the last two decades. It is now apparent that the total number of multiple 	pregnancies in any country represents the sum of the number of natural multiple pregnancies plus the number of 	IMPs. Neither component is fixed. Even if one recognizes that naturally occurring multiple pregnancies vary greatly 	by race (highest in women of African descent and lowest among Asian women), the number of IMPs is increasing in 	both developed and developing countries. Published data on twinning rates are often suspect because, in many instances, 	they are based on nonrepresentative, older, hospital-based studies.

 Even in the 	United States, where virtually 100% of births are reported, no central agency published reliable numbers of higher-order 	births above quadruplets until very recently. Furthermore, there are no means to differentiate a set of twins or 	triplets that represents the "remainder" of a reduced quintuplet or higher-order pregnancy from a set 	of naturally occurring or ART-created twins or triplets.

 In the United States, the total number of live births in multiple deliveries rose to the all-time high of 101,709 	by 1995.4 This number represents a 46% increase from 69,676 in 1980. Moreover, the rate of multiple births increased 	from 19.3 per l000 live births in 1980 to 26.1 per 1000 live births in 1995, with the twin birth rate increasing 	from 18.9 to 24.8 per 1000 live births (+31%). The birth rate for triplets and other higher-order multiples increased 	even more steeply, from 37 per 100,000 live births in 1980 to 127.5 per 100,000 live births in 1995 (+245%). Among 	the births in the 1995 cohort, 4551 were triplets, 365 were quadruplets, and 57 were quintuplets or higher-order 	multiples.

 As shown in Table 1, twin birth percentages increased in major American 	racial groups. Table 2 shows the changes in higher-order births over a three-decade period.   

The clinical impact of what now can justifiably be termed an "epidemic" of multiple births is not 	reflected in the data presented above. All types of multiple pregnancies are associated with high rates of preterm 	delivery, low birth weight, and the increased costs of caring for preterm infants.

 	Luke et al's recent assessment of costs of multiples lays the blame where it should rest--that is, on preterm delivery 	rather than on plurality.

 Recent US data show the differences in the rates of 	preterm delivery and low birth weight among singletons, twins, and triplets (Table 3). This Table uses commonly 	accepted terminology for preterm (<37 weeks' gestation) and very preterm (<33 weeks' gestation) births, as 	well as for low birth weight (<2500 g) and very low birth weight (<1500 g). The trends illustrated in Table 	3 appear to be global.

 Unfortunately, comparable data for quadruplet and higher-multiple 	births are not available. Regardless, intuition dictates that the problems of preterm delivery and low birth weight 	are exaggerated in quadruplets and higher-multiple pregnancies.


 	Because infertility is not a disease, nor is it even life threatening, all forms of treatment are ultimately used 	to "grant a wish." Because in most instances patients are abjectly unaware of treatment consequences, 	the principle of Primum non nocere ("Above all do no harm") should guide physicians as they propose various 	therapeutic options. This latter statement is particularly true for pregnancies that might follow ART, as they 	have considerable potential to violate this ancient principle.

Whereas it is axiomatic that most infertile couples desire a single child, information about desires of infertile 	couples for multiples is scant. In 1995, Gleicher et al published a survey of 3800 consecutive unselected couples 	with infertility.

 Although their reported response rate of 15% is too low to 	impute validity to study results, two trends were apparent. First, whereas the desire for twins and triplets increased 	with the age of the couple ("Let's get it over with"), this desire was not apparent when participants 	were queried about quadruplets or quintuplets. And second, as the length of infertility increased, infertile couples 	became more receptive toward the concept of having a pregnancy with twins and triplets (in the absence of a concomitant 	increase in the desire to parent them).

 These data corroborate the impressions 	obtained from the medical director of the Center for Reproductive Medicine, the largest private infertility clinic 	in Germany, where service is provided to a multinational clientele.

 Older patients 	with longer histories of infertility treatment are more likely to ignore stated risks of IMP even after thorough 	counseling in their native language. In addition, patients from nonindustrialized countries (e.g., Turkey, Ukraine, 	Romania) and patients belonging to lower socioeconomic/educational classes are much more likely to openly express 	a desire for multiple pregnancy. In contrast, career-oriented women or couples from developed countries are more 	likely to be concerned with having a singleton pregnancy.


 	As is the case with natural multiple pregnancy, IMP following ART poses classic, well-known risks
 	to the mother, the fetus, and the family unit. Classic maternal risks mentioned in most standard texts
 	of obstetrics include the pentad of pre-eclampsia, postpartum hemorrhage, anemia, polyhydramnios, and preterm labor. 	In addition, cesarean delivery poses a distinct risk for bleeding, infection, thromboembolic phenomena, and, although 	rare, death. Finally, women who have had higher-order pregnancies may be at greater risk for cardiomyopathy than 	previously thought.

Classic short-term fetal risks include low birth weight and preterm delivery, as well as their consequences. 	Long-term problems include growth restriction, neurologic deficits, and cerebral palsy, all of which place enormous 	financial burdens on the family and on society.

To these concerns must be added potential psychosocial risks. The few data that are available come from outside 	the United States, but the themes appear to be universal.

 Reported problems 	include unrealistic expectations about parenting and attendant problems, marital strain, separation and divorce, 	financial hardship, and, notably, maternal depression.

 In one well-documented 	French follow-up study of mothers of triplets, Robin et al described the need for psychiatric intervention for 	the mother, father, or both parents, as well as the frequent use of psychotropic medications, particularly among 	mothers of triplets.


 	For nearly three decades, OB/GYNs have been refining their ability to obtain informed consent. As treatment modalities 	increase in complexity, physicians can no longer rely solely on a discussion of the risks, benefits, and alternatives 	in order to obtain informed consent. This is particularly true for ART, because the risks may be multigenerational, 	involving mothers and children. Moreover, the complexity of specific ART procedures mandates delivery of detailed 	information in understandable terms. This discussion may be simplified by the use of written handouts that explain 	treatment-specific risks and provide relevant numbers and percentages for a broad range of problems associated 	with the contemplated procedure.

Any individual attempting to obtain informed consent for ART, with its attendant risks of IMP, should remember 	the following: First, patients hear but often do not listen. Second, without listening, they do not comprehend. 	Third, without comprehending, they do not understand. And finally, without understanding, by default, they are 	no longer granting "informed" consent. A recent American College of Obstetricians and Gynecologists' 	committee opinion aptly noted that counseling should be considered an ongoing process, beginning before treatment 	decisions are made and continuing throughout the patient's care.

 In the case 	of ART, the consent process must include information about the potential for multifetal pregnancy and the associated 	maternal and fetal risks.


 	The ethical and economic issues surrounding ART and IMP are complex, and cannot be resolved with simple answers 	of "right" and "wrong." Four distinct points of view compete and thus constitute a "quadratic" 	ethical dilemma. The elements involve the competing positions of the patient, the physician, the business, and 	the payer:

Most patients desire a singleton pregnancy and hope to achieve it in a timely and cost-effective manner.

Infertility specialists generally must temper their personal desire to be beneficent with a recognition of 		patient autonomy.

Business managers of infertility programs desire to achieve high pregnancy rates in order to attract more patients.

The third-party payer desires to avoid the high cost of repeat treatment cycles and/or the attendant high cost 		of IMP.

Resolution of the quadratic ethical dilemma of IMP cannot occur without specific actions by all parties. The 	tasks for the patient are not insubstantial. First, she (and her partner, if applicable) must understand the risks 	of IMP for each therapeutic intervention undertaken or contemplated. Next, she must honestly assess her own potential 	for becoming pregnant. Third, she must once and for all confront the concept of "Enough is enough." Last, 	she must consider the alternative of adoption or accept the prospect of child-free living--that is, life without 	the possibility of parenthood.

Physicians are faced with no less daunting a task. First, they must recognize that beneficence--seeking the 	greater balance of benefits over harm--is not identical to nonmalfeasance--that is, doing no harm. Second, they 	must avoid judging the reasons behind patients' decisions while remaining alert to the multitude of outside pressures 	influencing such decisions.

With regard to the business aspect of ART, four factors strongly affect profitability, at least in this country. 	First, there is no national single-fee scale for ART and in vitro fertilization (IVF). Second, there are no real 	financial disincentives to discourage high IMP rates in private offices or reproductive clinics. Third, the potential 	presence of a single-fee scale might be construed as destructive of profitability incentives. And fourth, reasonable 	profit margins for freestanding reproductive units have never been determined. It is not known whether the present 	circumstances would prevail if better insurance coverage were available. A recent editorial by Gleicher outlines 	several strategies to effect such a change.

The two higher-order multiple births recently reported in the media focused enormous attention on those women 	who traditionally seek infertility treatment from OB/GYNs. Some observers might suggest that these patients do 	not represent women from all walks of life. This is true, as Caucasian women seeking infertility treatment are 	disproportionate in number relative to the general population. Others would insinuate that the public ultimately 	pays for treatments after delivery and for long-term care in the cases where disability should ensue. This is also 	true, and the Iowa and Texas cases represent prime examples of high and as yet undisclosed peripartum costs, which 	will necessarily be followed by long (and presently incalculable) survivorship costs. Other critics might point 	out that countries such as the United Kingdom, Germany, Scandinavia, and France strictly prohibit the type of treatments 	that occur regularly in the United States, and are willing to assume the consequences of a strictly controlled 	fertility industry.


 	The authors agree with Chervenak and McCullough that it is possible to develop a preventive ethical approach to 	IMPs that result from ART and IVF.

 With regard to ART, it is possible to satisfy 	the requirements of informed consent specific to the procedure contemplated, to inform patients of known IMP rates 	specific to the procedure contemplated, to fully discuss selective termination versus nonintervention if IMP were 	to occur, and to know before starting therapy whether the patient is unable to accept abortion or MFR as an option.

With regard to IVF, the policy of transferring no more than two embryos in any given cycle could be advocated, 	especially in younger patients. This method has been shown to be equally effective in this age group in terms of 	maintaining pregnancy rates while significantly reducing the number of multiples (especially higher-order multiples).

 If such a policy were to be implemented in the United States, however, it would not be 	acceptable to all practitioners. Some would express concern about lower pregnancy rates or the potential exclusion 	of specific couples because of financial considerations. Furthermore, such a policy could never achieve its potential 	in the absence of some form of external surveillance, a concept that would not be popular. Regardless of whether 	this policy or some variant would be adopted, it still would be possible to grade embryos to enhance the quality 	of transfers or to consider blastocyst transfer to enhance the pregnancy rate.

 	Given our present state of knowledge, the better the quality of the embryo, the lower the need to transfer multiple 	embryos to attain a singleton pregnancy.

Methods to avoid higher-order IMPs are now well discussed in the literature. In terms of ART, one can carefully 	select patients, tailor doses of hormones, monitor estradiol levels and the number of growing follicles, and cancel 	cycles when the risk of IMP becomes apparent.

 In terms of IVF, the principal 	action appears to be limitation of the number of embryos transferred.

 Secondary 	actions are the use of blastocysts and grading of embryos based on validated scoring systems in order to achieve 	high implantation rates with low numbers of embryos transferred. The use of MFR, in the opinion of the authors, 	should remain as a backup procedure in the manner addressed by Evans and colleagues.

 	Finally, the authors agree with Verhoeven's recent opinion that IVF, as well as all ART treatments, should be performed 	only by experienced practitioners with a sense of responsibility and ethical values.


 	In the opinion of the authors, the tenets of ethical practice involved in ART and the resultant IMPs do not differ 	in concept from those related to other, everyday physician-patient interactions. The ethical principles of beneficence 	and autonomy are at the core of such interactions. Respecting this absolute depends on recognizing and dealing 	with potential IMP before and after any contemplated ART procedure. Should physicians themselves not deal with 	these issues, it is conceivable that governmental commissions will be empowered to deal with them under the rubric 	of interstate commerce regulation.

    1. Keith L, Oleszczuk JJ. Iatrogenic multiple birth, multiple pregnancy, and assisted reproductive technologies. Int J Gynecol Obstet. 1999;64:11-25.

    2. Cusick W, Gleicher N. Multiple conceptions, implantation and prematurity. Assisted Reprod Rev. 1995;5:246-250.

    3. Bryan E. Twins and Higher Multiple Births: A Guide to Their Nature and Nurture. London, England: Edward Arnold; 1992.

    4. Monthly Vital Statistics Report. 1997;45:1-15.

    5. Luke B, Bigger HR, Leurgans S, Sietsema D. The cost of prematurity: a case-control study of twins vs singletons. Am J Pub Health. 1996;86(6):809-814.

    6. Derom R, Orlebeke E, Erikson A, Thiery M. The epidemiology of multiple births in Europe. In: Keith LG, Papiernik E, Keith DM, Luke B, eds. Multiple Pregnancy: Epidemiology, Gestation & Perinatal Outcome. London, England: Parthenon Publishing; 1995:145-162.

    7. Westergaard T, Wohlfahrt J, Aaby P, Melbye M. Population based study of rates of multiple pregnancies in Denmark, 1980-94. BMJ. 1997;314:775-779.

    8. Imaizumi Y, Nonaka K. The twinning rates by zygosity in Japan, 1975-1994. Acta Genet Med Gemellol. 1997;46:9-22.

    9. Imaizumi Y, Nonaka K. Rising trizygotic triplet rates in Japan, 1975-1994. Acta Genet Med Gemellol. 1997;46:87-98.

    10. Gleicher N, Campbell DP, Chan CL, et al. The desire for multiple births in couples with infertility problems contradicts present practice patterns. Hum Reprod. 1995;10:1079-1084.

    11. Verhoeven H. Presented at the 7th Winter School on Perinatal Medicine; February 18, 1999; Zermatt, Switzerland.

    12. Ikeda S, Hasegawa A, Nagai R. Peripartum cardiomyopathy of multiple pregnancy. Ryoikibetsu Shokogun Shirizu. 1996;14:170-173.

    13. Garel M, Blondel B, Kaminski M. Multiple births in couples with infertility problems. Hum Reprod. 1995;10:2748. Letter.

    14. Robin M, Kheroua H, Casati I. Effects of early mother-twin relationships from birth to age 3, on twin bonding. Acta Genet Med Gemellol. 1992;41:143-148.

    15. Robin M, Josse D, Tourrette C. Forms of family reorganization following the birth of twins. Acta Genet Med Gemellol. 1991;40:53-61.

    16. ACOG Committee on Ethics. Nonselective embryo reduction: ethical guidance for the obstetrician-gynecologist; April 1999. Technical bulletin 215.

    17. Chervenak FA, McCullough LB. Ethical aspects of iatrogenic multiples. In: Blickstein I, Keith LG, eds. Iatrogenic Multiple Pregnancy Clinical Implications. London, England: Parthenon Publishing; 1999. In press.

    18. Gleicher N. Strategies to improve insurance coverage for infertility services. Fertil Steril. 1998;70:1006-1008.

    19. Templeton A, Morris JK. Reducing the risk of multiple birth by transfer of two embryos after in vitro fertilization. N Engl J Med. 1998;339:573-577.

    20. Veeck LL, Davis OK, Rosenwaks Z. How to avoid multiple pregnancy during artificial reproductive treatment. In: Blickstein I, Keith LG, eds. Iatrogenic Multiple Pregnancy Clinical Implications. London, England: Parthenon Publishing; 1999. In press.

    21. Rynders PM, Jansen CAM. The predictive value of day 3 embryo morphology for blastocyst formation and implantation rate at day 5 in IVF. Hum Reprod. 1996;1:86. Abstract.

    22. Verhoeven H. Can we prevent higher order multiples? Presented at VII Winter School on Perinatal Medicine of the Polish Society of Perinatal Medicine, Zermatt, Switzerland, Feb 28, 1999.

Articles

This article discusses the nature of infertility treatment and its relation to infertile couples' desires for multiple pregnancy, the special risks of iatrogenic multiple pregnancy (IMP), the informed consent process in assisted reproductive technology, and the ethical dilemma of IMP and methods for its resolution.

Iatrogenic Multiple Pregnancy Epidemiology, Risks, and Ethical Dilemmas

 “It’s April  2003, we’re in Berlin at the Controversies in Obstetrics, Gynaecology and  Infertility Conference and next to me are two world-leading experts on multiple  pregnancy. Please could you introduce yourselves?” 
 
 

 “Well, I  would like to introduce my friend, Louis Keith, who is a Professor at  Northwestern University, Chicago. He is running the Centre of Multiple Births in  Chicago with his twin brother, Donald, and currently he is the Co-President of  the ICS International Society of Twin Studies, author of a zillion papers  related to multiple pregnancy and also with me on two books now and a lot of  papers in the past and in the future.” 
 
 

 “My friend Isaac Blickstein is Professor of  Obstetrics and Gynaecology at the Hebrew University in Jerusalem, a  professorship which he just got this last year and, I must say, a professorship  which is long overdue based on his acknowledged leadership in the world of  multiple pregnancies and those publications I’ve worked with him on; this is our  third book and it has been a pleasure, Isaac.” 
 
 

 “Could you  both tell me, you have almost a lifelong history of collaboration, when and  especially how did it start?” 
 
 

 “Well, it began in Helsingborg, Sweden, where  we met for the first time. It continued in Israel at a meeting that he was  chairman of, but it really began in Copenhagen, Denmark, when I looked at Isaac  and I said, 'Isaac, it’s time that you edit a book for your career' and then  what did you say, Isaac?” 
 
 

 “The idea  came forth and the layout of this book, Iatrogenic Multiple Pregnancy, was  written on napkins of SAS. It was conceived on the ground but born in the air.” 
 
 

 “Exactly, because when I suggested it to  Isaac, he said somehow or other in the words that came out, the words iatrogenic  pregnancy came out, and I said, that’s it, that is your book and he looked at me  like I was insane, probably many of the viewers would say, yes, you’re right,  Isaac, he’s nuts, but aside from that, that was a topic that became obvious to  us because there was nothing on it in a monograph form and then came the flight  to Dusseldorf to see a mutual colleague, Hugo Verhoeven, for dinner and by the  time we landed, we put the pile of napkins on the plate and said, Hugo, what do  you think, this is the outline for the new book on iatrogenic pregnancies and it  came to pass.” 
 
 

 “Yeah, and  then we continued with the collaboration on the triplet book which was published  a few months ago and this idea came from Louis actually, because we witnessed  this tremendous increase in triplets in the United States. This kind of multiple  pregnancy, this kind of obstetric challenge, is indeed the most important thing  now in perinatal medicine. 
 
 The most important, in our view at least, and Louis got the collaboration with  the company in the United States that sponsored our research, extensive research  of their database and I think without their help and without knowing the  material at hand, nobody before could analyse samples of more than 60 triplets,  100 triplets, and for the first time we analysed 3,000 sets of triplets and it  is the cornerstone of this triplet book.” 
 
 

 “Yes, and when the company asked us to do the  analysis, I remember saying to them distinctly, well, we could do the analysis,  I know the right person, meaning you, but the question is how do you present it  so that it isn’t just another paper that lies on your desk and the way to do it  was to build a book around this analysis in which we tried to do everything we  could to get the world’s best authorities to write about every aspect of triplet  pregnancies and it’s about 600 pages this book, something like that.” 
 
 

 “And then we  come to revision of your first book and I think it will be the textbook on  multiple pregnancy, forthcoming next year.” 
 
 

 “Next year, 2004, if everybody is willing and  able to contribute their chapter on time. It will have 84 chapters.” 
 
 

 “At least, and it will represent not a  revision but a complete re-write with very few carry-overs from the first book.  Obviously, the chapter on conjoined twins isn’t going to change except we are  going to add to that a chapter by a young man in Poland who was instrumental in  the successful separation of a set of twins and it shows you really what can be  done now by internet and e-mail because the analysis of the children  pre-operatively was directed by a Doctor Scott Adsik at the Children’s Hospital  of Philadelphia in a series of e-mails to a former student of mine in Lublin,  Poland, who got every one of the tests performed in Lublin, digitised all the  results, sent them by e-mail, they were downloaded in Philadelphia, interpreted  in Philadelphia, the most complex types of tele-medicine that you could imagine,  and then the children were brought over courtesy of LOT Airlines, met at the  airport by the Polish counsel, whisked through customs and everything, every  courtesy was given, and they were ultimately successfully separated at the  Children’s Hospital of Philadelphia. 
 
 At the time, they were very skittish about having the newspapers know and there  was no publicity, but now that it’s over and now that the children are running  around like two other children of their age with very minimal scars, this is  going to be added to that chapter. But the rest of the chapters are essentially  new.” 
 
 

 “Yes, I  agree, because everything changed during the last decade, since 1995, when your  first book appeared because I think there are few topics in medicine that got so  much energy in it from all parts involved. I mean reproductive medicine is  nothing similar to what it was ten years ago. Neonatal medicine is nothing  similar to what it was ten years ago and perinatal medicine, ultrasound,  everything, is nothing like what it was before, so we had to change, even if the  outline is approximately similar, every chapter would be totally revised where  we would recognise or developed previously.” 
 
 

 “And I think that the situation with  multiples, of which twins are clearly the most common, is a worldwide epidemic,  there is no other terminology to explain it. Not only are women older when they  want to get pregnant, but many of them need help and, of course, you have all of  these twins. 
 
 When I’ve been studying the literature on twins since the mid-70s, you know, a  dataset of a 1,000 sets of twins in the mid-70s was an astronomical number, but  now there are many community hospitals when they want to review their data  internally, they have a 1,000 sets of twins in the last decade, so you just have  to put all this information together in a compendium.” 
 
 

“I totally  agree with you. I suppose that is what happened in terms of higher-order  multiples. I think that in one year, there were more high-order multiples  delivered in the United States than in the previous decade and 1998 was the  hallmark of the triplets. In 1998 alone there were more triplets born to mothers  over 35 than in the entire decade before and no other adjective like epidemic  can describe it. I mean, it is also contagious because it comes from one country  to another and from one developing country to another developing country and now  all countries have their own rate of infertility and couples want their children  and the risk of high-order multiples or multiples with infertility treatment is  equal, whether it is in the United States or in India, it is the same risk.” 
 
 

“And I think that’s one of the points that  we’re going to bring out very clearly in this revision, that it is absolutely  crucial that when women go to any form of assisted reproductive technology that  they be thoroughly informed of these risks. Not only should they go for some of  the more sophisticated manipulative types of therapy, but when they get the  simple drugs like clomiphene citrate, people don’t realise when they go to the  PDR in the United States and look at clomiphene citrate, it will give you the  dose but unless you read the fine, fine print, you won’t realise that the  references for which this dosing is made are forty years old. 
 
 Now, when you think about that, we certainly know that the results that we’re  getting with clomiphene today are not the results that were originally given to  the FDA forty years ago, but this doesn’t come out. It will certainly come out  in the book.” 
 
 

 “Yes, sure,  but I mean in iatrogenic pregnancies, that’s two kinds of iatrogenic multiples,  those who may be avoidable and those who may not be avoidable. I think that once  you stimulate the ovary, whether with clomiphene citrate or with gonadotrophins,  the ovary is stimulated and unless you abort the cycle, you cannot know exactly  how many multiples will come out or if it will be a singleton at all. 
 
 However, the avoidable cases are those in which you are yourself putting in the  number, you are deciding on the number of embryo transfers during an assisted  reproductive technology cycle. For example, in IVF, you are in charge of how  many embryos will be transferred and now the trend is in Scandinavia, for  example, is to minimise the risk of multiple pregnancy, more cycles with less  embryo transfer as opposed to doing everything necessary in order to achieve a  pregnancy and, in many ways, it is existentialistic position of the IVF centres. 
 
 They must have success. If they are not successful in getting a pregnancy, they  don’t have any role in medicine and, at certain times, it may result in a higher  rate of multiple pregnancies which are a complication of the treatment.” 
 
 

 “But this need to have success, I can  certainly understand from the point of view of the IVF centre. But in the last  two or three years, there has been a very critical review of what is success. We  were both in Australia and heard a paper from the people in Sydney, called IVF  Sydney, where they were so alarmed at their 41% twinning rate with, I think it  was two embryo transfers, they decided to do a trial where they only put in one  embryo and they got almost the same success rate in terms of total pregnancy  rate, but they brought the twinning rate down to 6%. 
 
 Now, in that regard, there have been some papers that are in the process of  being written now in the UK, which looks at all of the data for the entire  country and there they have shown it is absolutely economically feasible to put  an upper limit on the number of embryos transferred and spend the extra money on  giving more cycles because they will save so many days in the NICU units and the  costs that are associated with that, that it would pay the National Health  Service of England to give out more cycles and they would still save money  rather than paying these astronomical NICU bills because in the end, it is  society that pays the NICU bills. 
 
 We think of a couple in Israel or in Chicago or wherever, going to an IVF  centre, public or private, they pay or they don’t pay, and you can cost out this  at X, but that’s a given thing and that’s what people have in their mind. They  don’t think about two additional costs: Y and Z. Y is the neonatal intensive  care costs and Z is the lifetime cost of bringing up children who may be  neurologically impaired and whether we want to, we certainly don’t say that this  is wonderful, but we have to admit the truth of it. Not every higher-order  multiple child survives without neurological impairment and you have done some  studies to that effect.” 
 
 

 “Yes. We  calculated the risk of cerebral palsy, the quadriplegic type, which means the  baby or the child can’t move anything except his head and living in the  wheelchair for his lifetime, and the risk is about sixfold increased when there  is transferred three embryos and this idea was picked up by John Kiley from the  National Centre of Health Statistics and he did a study with me and it seems  that assisted reproductive technology in the United States adds 8% to the  cerebral palsy rate and if we do everything for it, every pregnancy, we do  seeing them daily, we do ultrasound weekly, we screen for every virus, every  bacteria, we do whatever is needed for pregnancy, amniocentesis, whatever we do,  we cannot reduce the cerebral palsy rate by 1%. However, with assisted  reproductive technology, we increase the numbers tremendously, 8% increase,  because the main idea is that we cannot avoid prematurity in these high-order  multiples and prematurity is definitely associated with neurological handicap.” 
 
 

 “And with that, perhaps, we ought to bring  this interview to a close and say to our listeners if you want to know more . .  . 
 
 

 “Well, it isn’t a question of buying our book,  it’s a question of looking forward to the publication. Let’s hope that we both  survive going through these 80 chapters to get it out on time in 2004. Thank  you, Isaac.” 
 
 

OBGYN.net Conference Reportingfrom the 4th World Congress on Controversies in Obstetrics, Gynaecology and Infertility

The Expanding World of Multiple Gestations

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Louis Keith, MD

Articles

Iatrogenic Multiple Pregnancy Epidemiology, Risks, and Ethical Dilemmas

The Expanding World of Multiple Gestations

The Expanding World of Multiple Gestations Video