Hum. Reprod. Advance Access originally published online on October 18, 2006
Human Reproduction 2007 22(2):624-626; doi:10.1093/humrep/del405
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Letters to the editor |
On the benefit of assisted reproduction techniques, a comparison of the USA and Europe
1 The Center for Human Reproduction—New York, New York and The Foundation for Reproductive Medicine, Chicago, IL, USA and 2 Department of Obstetrics and Gynecology, Allgemeines Krankenhaus and University of Vienna School of Medicine, Vienna, Austria
To whom correspondence should be addressed. E-mail: ngleicher{at}thechr.com
Sir,
We were interested in the letter by the European IVF monitoring (EIM) group (Nygren et al., 2006
) in response to our recent article (Gleicher et al., 2006).
Nygren et al. ‘did not necessarily agree’ with our opinion that significantly (in non-medical lingo dramatically) lower pregnancy and delivery rates in Europe ‘do not appear to benefit the European population’. Instead, they conclude that although ‘efficacy is higher in the USA, the benefit (to the population) may not be’. We believe that their arguments are not supported by facts.
EIM, indeed, uses selected data and statements from our article in support of their arguments: For example, we had noted, and EIM emphasizes in their letter, that the costs [of assisted reproduction techniques (ARTs)] in Europe are lower (as all medical costs are), insurance coverage is broader, utilization of ART cycles is twice that of the USA and ‘most importantly that the multiple pregnancy rates for twins and high-order multiples are much lower (in Europe), leading, of course, to much lower neo- and post-natal care costs’.
Summarizing all of these facts, EIM concludes that European patients may be privy to poorer efficacy in their ART treatments but do not receive less of a medical benefit. We, however, fail to understand how average differences in chance to conceive per treatment effort in all forms of ART (fresh, frozen–thawed and egg donation cycles) at an approximate range of 50%, and mandating approximately twice the US ART utilization, can be seen as anything but less benefit for the European patient.
The reader of this discourse is asked to imagine for a moment what the sentiments would be if European cardiac surgery rates were twice those of the USA (although of course at considerably lower cost per procedure) but European cardiac mortality after surgery was twice that of the USA? Would the European public consider such an approach as, indeed, more beneficial, simply because European costs per procedure are lower?
Our European colleagues then go on to argue that lower multiple pregnancy rates in Europe quite obviously reflect benefit. We, indeed, discussed this point quite extensively in our article and, of course, have to agree with a general goal of fewer multiple births (Gleicher and Barad, 2006). We, however, also quite conclusively demonstrate in our article that larger embryo numbers transferred, resulting in higher multiple pregnancy rates, contribute only to a minor degree to the overall much better pregnancy rates in the USA.
As everybody seems to agree, multiple pregnancies, indeed, appear to incur significantly higher "costs" than singletons (Gleicher et al., 2000). However, a more careful economic analysis of this issue may have to come to different, and maybe somewhat surprising, conclusions. Let us first define the term ‘benefit’, in this case, of course economic benefit, because our European colleagues appear to define benefit, in this context, as mostly a monetary value. We previously pointed out that such an approach, in our opinion, was misguided because, amongst other shortcomings, it fails to consider a patient’s right to self-determination, i.e. to choose a multiple birth (Gleicher and Barad, 2006). Most patients would consider such a right as a very strong benefit of their treatment.
However, let us for a moment accept that monetary criteria are, indeed, driving the issue. Even under such an obviously incorrect assumption, EIM’s arguments would, most likely, still be wrong if costs were analysed correctly. Any fair economic analysis of costs and benefits of multiple births cannot, of course, end up with only the calculation of neonatal care costs, as most studies have done. They also must include the life-long carrying costs for severely handicapped individuals (greatly increased amongst multiple births) but can also not forget to consider the life-long earning ability of the large majority of multiples who are not incapacitated. It remains to be seen whether such an economic analysis will uphold the generally assumed economic disadvantage of multiple births. A large majority of infertile patients worldwide apparently do not believe so because, if given the chance, they would, indeed, choose a multiple birth (Gleicher and Barad, 2006).
Nygren et al. then also accuse us of outright biases because ‘Europe is far from homogenous’. They may, indeed, be correct when arguing, ‘country to country comparisons may be more informative’. However, if there is no value to the Europe-wide data, then one has to ask why the European Society of Human Reproduction and Embryology (ESHRE), in the first place, goes through the efforts of publishing those in the pages of this Journal? These authors are also mistaken when indirectly implying that US data, in contrast, are homogenous. Indeed, a careful review of the annually published outcome reports for all ART clinics in the USA will prove quite convincingly the opposite.
To suggest that our conclusions were ‘biased’ would, therefore, appear to be unfair. Indeed, we repeatedly pointed out in our article how difficult certain statistical comparisons were between the two continents and urged caution in the interpretation of data where they were not clearly documentable on both sides of the Atlantic.
Nygren et al. also accuse us of not having considered ‘difference in clinical policies’, such as differences in patients selection (other than age), aggressiveness of stimulation, cycle cancellation rates (higher in the USA) and fetal reduction policies. Although differences in such practice patterns may, indeed, exist, we fail to understand how any one (or more) of them could serve as an excuse for the significantly inferior pregnancy outcomes in Europe. For example, is the USA selecting patients better or worse than Europe? We, indeed, do not know the answer to this question, but would it not behove Europe to find out in an attempt to better their outcomes? Or would it not be appropriate for Europe to attempt to determine whether the USA, indeed, stimulates patients differently because, after all, their outcomes are dramatically better all across the spectrum? It is, of course, differences in practice patterns that cause the outcome differences between Europe and the USA. However, considering such practice differences as arguments in defence of such outcome differences would appear quite non-sensical.
We are pleased to agree with one point in the letter by Nygren and associates: an improved comparison of practice patterns would be possible if cumulative pregnancy rates could be reported for ART cycles. Indeed, we have argued in our article for a unified method of outcome reporting between ESHRE and Society for Assisted Reproductive Technologies (SART)/American Society for Reproductive Medicine (ASRM). The authors of the letter then, however, become anecdotal in their argument when stating that ‘the transition towards transfer of less embryos has been more rapid in at least parts of Europe, one of the consequences being more frozen cycles...’.
Our original comparison between European and the US outcomes was made for the year 2001. We just completed a similar comparison for the only recently published (European) 2002 data. In contrast to the statement made by Nygren et al., Europe showed a much smaller increase in the number of frozen cycles than the USA and a slower decline in multiple pregnancy rates, when outcomes between these two years were compared. On a side note, pregnancy outcome differences between the continents also continued to increase, as did the utilization gap (N. Gleicher et al., unpublished results). This, of course, does not mean that individual countries, especially in Scandinavia, where the change towards single embryo transfer has been most active, may not diverge from these European data. However, individual countries were not the subject of our article, and our arguments were made vis-à-vis the European database, published by ESHRE.
Having expressed such considerable disagreement with the letter by Nygren et al., we do agree with their concluding remarks. We, indeed, should report outcomes ‘in more sophisticated and synchronized ways to make comparisons possible and more meaningful. ART professionals in Europe should scrutinize ART programs in the USA to learn whether some clinical and laboratory routines may be better performed (there). Additionally, US professionals should reduce the number of embryos they transfer’.
We also agree with our critics that the ultimate causes for the very significant outcome differences between Europe and the USA are still unknown. We, however, maintain our belief that at least part of this difference can be traced to the rigidity of, at times, legal and, at other times, professional mandates, which US professionals do not have to face. European patients will find significant benefits in a liberalization of the patient–physician relationship, which recognizes both parties’ primary interest in superior clinical outcomes, in the absence of rigid governmental or professional orthodoxy.
References
Gleicher N and Barad D. (2006) The relative myth of elective single embryo transfer. Hum Reprod 21:1337–1344.
Gleicher N, Oleske D, Tur-Kaspa I, Vidali A, Karande V. (2000) Reducing the risk of high order multiple pregnancy after ovarian stimulation with gonadotropins. N Engl J Med 34:2–7.
Gleicher N, Weghofer A, Barad D. (2006) A formal comparison of the practice of assisted reproductive technologies between Europe and the USA. Hum Reprod 21:1945–1950.
Nygren K, Nyboe Andersen A, Felberbaum R, Gianaroli L, de Mouzon J. Members of ESHRE’s European IVF Monitoring (EIM). (2006) On the benefit of assisted reproduction techniques, a comparison of the USA and Europe. Hum Reprod 21:2194.
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