Safety versus success in elective single embryo ... - Wiley Online Library

DOI: 10.1111/j.1471-0528.2007.01396.x

Fertility and assisted reproduction

www.blackwellpublishing.com/bjog

Safety versus success in elective single embryo transfer: women’s preferences for outcomes of in vitro fertilisation GS Scotland,a P McNamee,a VL Peddie,b S Bhattacharyab a Health Economics Research Unit, University of Aberdeen, Foresterhill, Aberdeen, UK b Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Aberdeen, UK Correspondence: Dr GS Scotland, Health Economics Research Unit, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. Email [email protected]

Accepted 16 April 2007. Published OnlineEarly 18 June 2007.

Objective To assess whether women waiting to undergo in vitro

fertilisation (IVF) view adverse outcomes associated with twin pregnancy as more desirable than having no pregnancy at all. Design Women’s preference values for five adverse birth

outcomes associated with twin pregnancy were compared with their preference value for treatment failure (TF), i.e. no pregnancy at all. Setting Aberdeen Fertility Centre, University of Aberdeen, UK. Population A total of 74 women waiting to undergo IVF. Methods The standard gamble method was used to elicit women’s

preference values for giving birth to a child with physical impairments (PI), cognitive impairments (CI), or visual impairments (VI), perinatal death (PD) without a subsequent pregnancy, premature delivery (PremD), and TF (no pregnancy).

Main outcome measures Preference values were elicited on a scale where 1 represents giving birth to a healthy child and 0 represents immediate death. Results The median preference values for having a child with PI, CI, or VI were 0.940, 0.970, and 0.975, respectively. The median values for PremD, PD, and TF were 0.955, 0.725, and 0.815, respectively. Having no child at all was valued significantly lower than having a child with PI, CI, or VI (P < 0.01) but significantly higher than PD (P < 0.01). Conclusions Some women waiting for IVF treatment view severe

child disability outcomes associated with double embryo transfer as being more desirable than having no child at all. Women embarking on IVF may be influenced more strongly by considerations of ‘treatment success’ rather than future risks to their offspring. Keywords IVF, multiple pregnancy, patient preferences,

single embryo transfer.

Please cite this paper as: Scotland G, McNamee P, Peddie V, Bhattacharya S. Safety versus success in elective single embryo transfer: women’s preferences for outcomes of in vitro fertilisation. BJOG 2007;114:977–983.

Introduction The traditional practice of transferring two or more embryos during in vitro fertilisation (IVF) treatment has led to a 20fold increased risk of twins and a 400-fold increased risk of higher order multiples.1 Although a policy of double embryo transfer (DET) has reduced the number of triplet pregnancies in Europe, the twin pregnancy rate is still unacceptably high at 24%.2 This is of concern as twin pregnancies are associated with increased morbidity and mortality for both mother and child,3 as well as increased costs to the health service.4 Elective single embryo transfer (eSET) is an effective method for reducing twin pregnancies resulting from IVF. However, some uncertainty remains as to whether eSET can produce live birth rates similar to those achieved with DET.5

Several European countries have changed their policies making eSET compulsory for certain groups of women.6 However, in countries such as the UK, where funding for multiple IVF treatments is limited and couples are given a choice over the number of embryos transferred, uptake of eSET has tended to be low.2 The Human Embryology and Fertilisation Authority in the UK commissioned an expert panel to review the evidence on multiple births and single embryo transfer in 2005. The following two possible solutions to the problem have been proposed: (1) to set clinics a maximum twin birth rate which should not be exceeded; or (2) to develop criteria for selecting groups of women who should be offered eSET based on their risk of multiple pregnancy.7 It is unclear how either of these policies would be implemented, but the report recognises the

ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology

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need for professional bodies and clinics to improve patient information on the risks associated with twin pregnancy to improve acceptance of eSET. However, previous studies suggest that acceptance of eSET is likely to be low, even if women are made aware of the extra risks associated with DET.8,9 Murray et al.8 found that neither the provision of additional information on the risks nor changing the way in which it was delivered had any impact on couples’ attitudes to twin pregnancy and eSET. A possible explanation for the poor uptake of eSET is that women believe that it will reduce their chance of a live birth. In addition, some women have a preference for twins,10–12 and some may view the adverse outcomes associated with DET and twin pregnancy as acceptable risks in light of the perceived higher chance of a live birth.13 This apparent discounting of the extra risks associated with DET may partly explain the poor uptake of eSET. To test this hypothesis, we assessed women’s preference values for a range of adverse birth outcomes associated with twin pregnancy. We next compared these values to the value they placed on treatment failure (TF), i.e. no pregnancy at all. We used the standard gamble method—a risk-based technique for measuring health state preferences—to elicit the preference values of women who were waiting to undergo IVF treatment.14

Methods The study was conducted at the Aberdeen Fertility Centre, Aberdeen Maternity Hospital, Aberdeen, UK, from November 2004 to March 2006. A total of 226 women waiting to undergo IVF were invited to participate in a valuation interview. Those women who had past experience of any adverse birth outcomes were excluded on the grounds that the interview might evoke traumatic recall. The study was approved by the Grampian Research Ethics Committee, and all respondents gave prior written informed consent.

Descriptions for each outcome were developed through literature review and consultation with clinical experts.15 Descriptions for the three child disability outcomes (PI, CI, and VI) were loosely based on the descriptive system of the Health Utilities Index, Mark 2,16 while the other descriptions were brief narratives communicating the key points that each outcome would entail. All descriptions are provided in the Appendix.

Interview protocol Each woman was interviewed in a private clinic room by one of the authors (G.S.). First of all, demographic information on the respondent’s was obtained. In addition, respondents were asked to state how long they had been waiting to receive IVF treatment and their planned source of funding for treatment. Women were then asked to read the descriptions of the four lifelong birth outcomes (PI, CI, VI, and PD) and to imagine how they would feel if they were to become pregnant and go onto experience each of them. Following this, they were asked to rate the four birth outcomes on a visual analogue scale (VAS) where giving birth to a healthy child represented the best possible outcome (100) and immediate death for the mother and unborn child represented the worst possible outcome (0). Participants were asked to arrange the four birth outcomes on the scale so that the intervals between them reflected their relative strengths of preference—i.e. they were told to place outcomes similar in desirability close together and states of different desirability further apart. The main purpose of the VAS exercise was to get participants thinking about their relative preferences for the lifelong birth outcomes so they could be ranked from H1 (most preferred) to H4 (least preferred) before commencing the standard gamble questions. Following the VAS exercise, all of the outcome scenarios were valued using the standard gamble method (Figure 1). Participants were presented with a series of hypothetical

Outcome scenarios Five birth outcomes and one treatment outcome were chosen for valuation. Four of the birth outcomes were presented as lifelong scenarios: giving birth to a child with physical impairments (PI), giving birth to a child with cognitive impairments (CI), giving birth to a child with visual impairments (VI), and experiencing a perinatal death (PD) without a subsequent pregnancy. For the fifth birth outcome, premature delivery (PremD), the child’s survival, and longterm outcome were left unspecified so that we could assess how women felt about the prospect of experiencing the uncertainty and anxiety that goes with having a very PremD. The TF valued in the interview was a scenario where all treatment failed, and there was no pregnancy for the duration of the women’s life.

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Figure 1. Representation of a standard gamble valuation question where a child disability outcome is valued relative to giving birth to a healthy child (1) and experiencing a PD followed by no subsequent pregnancy (0). The probability that renders the participant unable to choose between alternatives 1 and 2 provides the utility score for the outcome of the certain option.


Women’s preferences for outcomes of in vitro fertilisation

scenarios where they faced the prospect of either definitely experiencing one of the six outcomes chosen for valuation (PI, CI, VI, PD, PremD, or TF) or taking a risky treatment option. The risky treatment option not only gave them a chance (P) of giving birth to a healthy child but also a chance (1–P) of a worse outcome (e.g. PD). The probabilities of success (birth of a healthy child) that rendered the individual indifferent (unable to choose) between the certain and risky treatment options in the different gambles were elicited in one of two ways: either by systematically varying the probability (using 5% increments) until the respondent became indifferent between the two options (format 1)12 or by asking subjects to state the minimum probability of achieving the success outcome (birth of a healthy child) they would require to choose the risky treatment option (format 2). These probabilities of indifference provide a measure of the respondent’s preference value for the certain outcome on a scale where 1 represents the preference value for the success outcome of the uncertain option and 0 represents the preference value for the failure outcome. Women were randomly assigned to one or other of the preference elicitation formats. This was performed to investigate a methodological question relating to the internal consistency of the standard gamble technique, which is the subject of a separate analysis. Although format 2 resulted in higher values relative to format 1, both gave exactly the same results in terms of ordering of preferences. Therefore, the data have been combined for this analysis (results by format available from the authors). The valuing of outcomes proceeded are as follows. First of all, the four lifelong birth outcomes (PI, CI, VI, and PD) were valued relative to giving birth to a healthy child and death for the mother and unborn child during pregnancy. Following this, the lifelong birth outcomes ranked from H1 to H3, PremD and TF were valued relative to giving birth to a healthy child and H4 (experiencing a PD in all except three women). In addition, four participants felt that TF was worse than experiencing a PD. In these cases, TF was valued in a gamble where it represented the adverse outcome of the uncertain option, and H4 represented the certain option.

Statistical analysis All the values reported in this paper are adjusted to a common scale—where 0 represents death for the mother and unborn child during pregnancy and 1 represents giving birth to a healthy child—using a two-step procedure. Values obtained relative to giving birth to a healthy child and a worse health outcome (other than maternal/fetal death) were linked to this scale through a second gamble where the worse outcome was valued relative to giving birth to a healthy child and death for the mother and unborn child. Nonparametric tests were used to analyse differences in preference values as distributions were found to be non-normal. Friedman two-way analysis of variance (ANOVA) and Wilcoxen signed rank tests were

used to test for within group differences in median preference scores, and Kruskal–Wallis one-way ANOVA and Mann– Whitney U tests were used to test for relationships between utility scores and demographic variables.

Results Of the 226 women invited to participate in an interview, 81 (36%) women agreed to participate. Seven interviews were excluded from the analysis due to inconsistencies in responses—i.e. the rank ordering of preferences (for the four lifelong birth outcomes) implied from responses to the standard gamble questions were completely inconsistent with the rank ordering elicited directly using the VAS. In addition, six women did not complete all the standard gamble questions resulting in five missing values for outcomes PI, CI, and VI, four missing values for PD, and four missing values for TF. The characteristics of those 74 women included in the analysis are shown in Table 1. Results of the VAS exercise for the four lifelong birth outcomes are shown in Table 2. These results indicate that participants preferred the prospect of having a child with each of the lifelong disability outcomes to the prospect of

Table 1. Demographic characteristics of women included in the analysis Demographic characteristics

n 5 74

Mean age in years (SD) 31.7 (4.07) Number of women with existing children, n (%) 5 (6.8) Main activity, n (%) Employed/self-employed 67 (90.5) Housework 4 (5) Student 2 (3) Other 1 (1.5) Schooling, n (%) Minimum school leaving age 62 (83.8) Beyond minimum school leaving age 12 (16.2) Have degree or equivalent professional 31 (46.3) qualification* Planned funding source, n (%)* NHS 28 (42) Self 22 (33) Uncertain 17 (25) Average time on IVF waiting list (SD)** 10 months (7.03) Had other fertility treatments* 27 Familiarity with complications through 45 (68.2) family or friends, n (%)* *Data missing for seven women due to addition of demographic variables after first ten interviews. **Data missing for seven women (as above*) and for another seven women due to inability to recall the information.


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Table 2. VAS results

Discussion

Outcome

Median score (interquartile range)

Giving birth to a child with PI Giving birth to a child with CI Giving birth to a child with VI PD followed by no subsequent pregnancy

55 (35.8–70) 75 (59.3–85) 80 (66.5–90) 10 (2.8–20)

All scores are expressed on a scale where 100 represents giving birth to a healthy child and 0 represents death for mother and unborn child during pregnancy.

experiencing a PD with no subsequent pregnancy (P < 0.01, Wilcoxen signed rank test). The results for the standard gamble valuations are shown in Table 3. There were significant differences in preference scores across the different outcomes (P < 0.01, Friedman two-way ANOVA). The median preference scores for giving birth to a child with PI, CI, and VI were 0.940, 0.970, and 0.975, respectively. Experiencing a PremD was valued at 0.955. PD and TF were valued lower at 0.725 and 0.815, respectively. Having no child at all was valued significantly lower than having a child with PI, CI, or VI (P < 0.01, Wilcoxen signed rank test) but significantly higher than PD (P < 0.01, Wilcoxen signed rank test). The number of participants who valued each of the lifelong birth outcomes higher, equal to, or lower than the TF scenario is shown in Table 4. There were no differences in median preference scores (or ordering of preferences) between subgroups defined by age (35 years), employment status, education level, or duration of time spent on the IVF waiting list (1 year). There was also no difference between self-funding women (who do not have to wait for treatment) and women waiting for NHS funded treatment. In addition, previous fertility treatment and familiarity with the birth outcomes being valued (through having family or friends who had experienced them) had no effect on preference values.

Table 3. Standard gamble results Outcome

Median (interquartile range)

Giving birth to a child with PI Giving birth to a child with CI Giving birth to a child with VI PD followed by no subsequent pregnancy PremD TF (no pregnancy for duration of life)

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0.940 (0.85–0.996) 0.970 (0.9–0.999) 0.975 (0.922–1) 0.725 (0.4–0.925) 0.955 (0.875–0.994) 0.815 (0.712–0.977)

The results indicate that women waiting for IVF treatment would prefer to give birth to a child with a chronic disability than never give birth at all. When faced with the prospect of never experiencing childbirth, most women were willing to accept a significantly greater risk of experiencing the worst possible outcome for their children than when faced with the prospect of a chronic disability outcome for their child. This suggests that the prospect of experiencing a live birth is of utmost importance to women and that risks to potential offspring may be given less weight when making decisions regarding infertility treatment. This adds weight to our hypothesis that women discount the risks associated with DET and provides an explanation for low uptake of eSET in the UK. A weakness of our study is the low response rate for interviews (36%). This probably relates to the time implications of attending a separate interview appointment. Due to ethical constraints, we were unable to collect any data on those who declined, but compared with the total population undergoing IVF at the Aberdeen Fertility Centre during the course of the study, the average age of participants was lower (31.7 versus 35.0 years). The difference arises because many participants still had a substantial period of time to wait before they reached the top of a 2–3 year IVF waiting list. The percentage of participants planning NHS funded treatment (42%) was comparable with the percentage of IVF women actually receiving NHS funded treatment at the unit (42%). Although a secondary analysis suggests that the age, waiting time, and funding do not affect preferences, other factors may limit the generalisability of the findings. In settings where multiple funded cycles are available, for example, there will be less pressure on women to achieve success in their first cycle and so adverse consequences of twins may be given more careful consideration by couples. It should also be noted that only 6.8% of participants had existing children compared with 30% of the population undergoing IVF. This may partly account for the unwillingness of participants to consider the potential complications of multiple pregnancy, and their apparent desire to achieve a pregnancy at all costs. Another potential weakness is that, due to the nature of the standard gamble, the lifelong birth outcomes and the TF scenario had to be valued from different reference points. The standard gamble works by presenting respondents with a hypothetical situation where, unless they accept a risky treatment option, they face the certainty of an intermediate adverse outcome. To present each of the adverse birth outcomes as certainties, we had to ask women to imagine that they had become pregnant but had developed some complications. The uncertain option then took the form of a treatment, which if successful would result in the birth of a healthy child but if unsuccessful would result in an outcome worse



Table 4. TF versus lifelong birth outcomes Outcome

Giving birth to a child with PI Giving birth to a child with CI Giving birth to a child with VI PD

Number of participants valuing each lifelong birth outcome Higher than the TF

Equal to TF

Lower than TF

47 53 54 5

11 11 11 8

10 4 3 57

than the certain option. For the TF scenario, the certain option was never becoming pregnant and the uncertain option was framed as a new experimental treatment, which could result in the birth of a healthy child but would otherwise result in PD. Therefore, the birth outcomes were valued from the reference point of being pregnant, and the TF scenario was valued from the reference point of not being pregnant. This difference in reference point may have contributed to the difference in values observed between the lifelong birth outcomes and the TF scenario. However, as all the scenarios were valued relative to the same anchor states in the standard gamble interviews, the values obtained are on a common scale, despite the difference in reference point. In addition, all except three women valued PD with no subsequent pregnancy lower than all the lifelong child disability outcomes. This highlights the importance women place on having a child, regardless of health status. Our findings are broadly consistent with the literature on the acceptability of multiple pregnancy and eSET to couples receiving IVF treatment. A number of studies have found that couples are accepting of multiple pregnancy as a potential outcome of IVF treatment, despite being aware of the associated risks.8,13 Indeed, there is evidence to suggest that a substantial number of women have a direct preference for twins at the time they receive treatment.10–12,17,18 Our finding that women place high value on adverse birth outcomes associated with twin pregnancy (other than PD with no subsequent pregnancy) might partly explain this. If women do not feel the outcomes themselves are so bad, they are unlikely to be put off by risks of them occurring. This is at odds with the views of many clinicians who cite complications of twin pregnancy as the main argument in favour of eSET.19 A number of other studies have used the standard gamble to assess the preferences of pregnant or postnatal women for different birth outcomes. Pham and Crowther20, and Vandenbussche et al.,21 found that women valued permanent neurological sequelae significantly higher than neonatal death. Vandenbussche et al. found that this was at odds with the preferences of obstetricians who tended to value permanent neurological sequelae lowest. Others have also found that healthcare professionals tend to provide lower preference val-

Total

68 68 68 70

ues for child disability outcomes than do parents.22 Another study found that pregnant women tended to place lower value on giving birth to a child with Down’s syndrome compared with losing a pregnancy due to antenatal testing and having no subsequent child.23 This contradicts our finding that women placed greater value on having a disabled child than on scenarios where treatment ultimately resulted in no child. This might be due to a difference in the way infertile women perceive child disability outcomes compared with women without fertility problems. If women waiting for IVF treatment do place different values on treatment outcomes to clinicians or the natural conception population, this creates some difficulty for evaluating the effectiveness and cost-effectiveness of strategies involving eSET.24 Most studies that have assessed the cost-effectiveness of such strategies have focused on the number of pregnancies resulting in the live birth of at least one child. A problem associated with this outcome is that it fails to capture the potentially adverse impact of undesirable birth outcomes associated with twin pregnancy. Min et al.25 proposed the birth emphasizing a successful singleton at term as an alternative outcome measure based on the assumption that all twin pregnancies are undesirable. This may not necessarily be the case in all circumstances, given the subjective way in which birth outcomes are valued. Others have proposed the term live birth rate (including twins with a gestational length >36 weeks) as a more suitable measure for this reason.26 However, our findings suggest that some women seem to prefer the prospect of a PremD to having no live birth at all, even if this were to result in a chronic disability outcome for the child. The preference measurement techniques used in this study provide a way of addressing concern over how best to incorporate important outcomes associated with fertility treatment that the live birth rate fails to capture. By using the preference values that different groups place on different birth scenarios, it would be possible to weight different IVF outcomes in cost-effectiveness analyses so as to identify the embryo transfer strategies that maximise expected benefit from different perspectives. Regarding the acceptability of eSET, our findings seem to support the conclusion that improved voluntary acceptance


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will require couples to be assured that their chances of having a child, any child, are not compromised.8,27,28 If infertile women do indeed place a higher value on adverse birth outcomes associated with twin pregnancy, compared with having no live birth at all, then it is unlikely that being informed of these risks will deter them from DET. A better way to encourage uptake would be to devise ways of packaging eSET (in terms of offering several cycles of fresh and frozen embryo transfers) so as to assure women that they have as good a chance of a live birth in the long run as they would with DET. If couples incur additional costs or use up one of their publicly funded treatment cycles by freezing and subsequently replacing spare embryos, this will act as a deterrent to opting for eSET. Such barriers will have to be removed if the uptake of eSET is to be increased voluntarily. Another factor that may encourage a preference for twin pregnancy and DET is the fact that in some parts of the UK, couples who have a child after successful treatment are no longer eligible for further funding. Therefore, some couples who wish to have more than one child, but cannot pay for additional treatments, perceive the increased chance of twins with DET as a bonus. Adding to the problem is the fact that, on average, more embryo transfers are required with eSET to achieve the same live birth rate as DET. Couples are more likely to opt for DET if they feel the treatment process is very stressful. In this respect, adoption of milder ovarian stimulation protocols may encourage better uptake.26 In summary, our results suggest that some women waiting for IVF treatment view severe child disability outcomes associated with DET as being more desirable than having no child at all. This is at odds with many clinicians’ perceptions of treatment success and might explain the reluctance of some couples to accept single embryo transfer, despite awareness of the risks of twin pregnancy. Women embarking on IVF may be influenced more strongly by considerations of ‘treatment success’ rather than future risks to their offspring, however, severe. Attempts to educate women of the risks associated with twin pregnancy may need to be accompanied by other mechanisms to make eSET more appealing.

Acknowledgements Thanks to all the staff at Aberdeen Fertility Centre, University of Aberdeen, UK, who helped identify and recruit women to participate in this study. Thanks to Valerie Angus and Alison McTavish for providing summary statistics on the demographic characteristics of women receiving IVF at the Aberdeen Fertility Centre.

Funding Funding for this study was provided by The Wellcome Trust. Financial support was also provided by the Institute of

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Applied Health Sciences, University of Aberdeen, UK. The Health Economics Research Unit is funded by the Chief Scientist Office of the Scottish Executive Health Department. The views expressed in this study are those of the authors and not necessarily those of the funding bodies. j

References 1 Martin PM, Welch HG. Probabilities for singleton and multiple pregnancies after in vitro fertilization. Fertil Steril 1998;70:478–81. 2 Anderson AN, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. The European IVF-monitoring programme (EIM), European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE. Hum Reprod 2006;21:1680–97. 3 Blondel B, Kaminsky M. Trends in the occurrence, determinants, and consequences of multiple births. Semin Perinatol 2002;26:239–49. 4 Ledger WL, Anumba D, Marlow N, Thomas CM, Wilson EC; Cost of Multiple Births Study Group (COMBS Group). The costs to the NHS of multiple births after IVF treatment in the UK. BJOG 2006;113:21–5. 5 Pandian Z, Templeton A, Serour G, Bhattacharya S. Number of embryos for transfer after IVF and ICSI: a Cochrane review. Hum Reprod 2005; 20:2681–7. 6 Gerris JM. Single embryo transfer and IVF/ICSI outcome: a balanced appraisal. Hum Reprod Update 2005;11:105–21. 7 Braude P. One Child at a Time: Reducing Multiple Births after IVF. Report of the Expert Group on Multiple Births After IVF. HFEA, 2006 [www.hfea.gov/en/485]. Accessed 15 November 2006. 8 Murray S, Shetty A, Rattray A, Taylor V, Bhattacharya S. A randomized comparison of alternative methods of information provision on the acceptability of elective single embryo transfer. Hum Reprod 2004;19: 911–16. 9 Porter M, Bhattacharya S. Investigations of staff and patients’ opinions of a proposed trial of elective single embryo transfer. Hum Reprod 2005;20:2523–30. 10 Gleicher N, Barad D. The relative myth of elective single embryo transfer. Hum Reprod 2006;21:1337–44. 11 Pinborg A, Loft A, Schmidt L, Andersen AN. Attitudes of IVF/ICSI-twin mothers towards twins and single embryo transfer. Hum Reprod 2003;18:621–7. 12 Leiblum SR, Kemmann E, Taska L. Attitudes toward multiple births and pregnancy concerns in infertile and non-infertile women. J Psychosom Obstet Gynaecol 1990;11:197–210. 13 Hartshorne GM, Lilford RJ. Different perspectives of patients and health care professionals on the potential benefits and risks of blastocyst culture and multiple embryo transfer. Hum Reprod 2002;17: 1023–30. 14 Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programmes, 3rd edn. Oxford, UK: Oxford University Press, 2000. 15 Furlong W, Feeny D, Torrance G, Barr R, Horsman J. Guide to Design and Development of Health-State Utility Instrumentation. CHEPA Working Paper; 90. Hamilton, Canada: McMaster University, 1990. 16 Feeny D, Furlong W, Barr RD, Torrance GW, Rosenbaum P, Weitzman S. A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer. J Clin Oncol 1992;10:923–8. 17 Ryan GL, Zhang SH, Dokras A, Syrop CH, Van Voorhis BJ. The desire of infertile patients for multiple births. Fertil Steril 2004;81:500–4. 18 Gleicher N, Cambell DP, Chan CL, Karande V, Rao R, Balin M, et al. The desire for multiple births in couples with infertility problems contradicts present practice patterns. Hum Reprod 1995;10:1079–84.



19 ESHRE Campus Report. Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. Hum Reprod 2001;16:790–800. 20 Pham CT, Crowther CA. Birth outcomes: utility values that postnatal women, midwives and medical staff express. BJOG 2003;110:121–7. 21 Vandenbussche FP, De Jong-Potjer LC, Stiggelbout AM, Le Cessie S, Keirse MJ. Differences in the valuation of birth outcomes among pregnant women, mothers, and obstetricians. Birth 1999;26:178–83. 22 Saigal S, Stoskopf BL, Feeny D, Furlong W, Burrows E, Rosenbaum PL, et al. Differences in preferences for neonatal outcomes among health care professionals, parents and adolescents. JAMA 1999;281:1991–7. 23 Kuppermann M, Shiboski S, Feeny D, Elkin EP, Washington AE. Can preference scores for discrete states be used to derive preference scores for an entire path of events? An application to prenatal diagnosis. Med Decis Making 1997;17:42–55. 24 Scotland GS, McNamee P, Bhattacharya S. Is elective single embryo transfer a cost-effective alternative to double embryo transfer? BJOG 2007;114:5–7. 25 Min JK, Breheny SA, MacLachlan V, Healy DL. What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction. Hum Reprod 2004;19:3–7. 26 Heijnen EMEW, Eijkemans MJC, De Klerk C, Polinder S, Beckers NGM, Klinkert ER, et al. A randomised trial comparing a standard vs. a mild treatment strategy, considering term live birth, cost and discomfort during 1 year treatment. Hum Reprod 2006;21 (Suppl 1):Abstract O–207. 27 Newton CR, McBride J, Feyles V, Tekpetey F, Power S. Factors affecting patients’ attitudes toward single- and multiple-embryo transfer. Fertil Steril 2007;87:269–78. 28 Blennborn M, Nilsson S, Hillervik C, Hellberg D. The couple’s decision making in IVF: one or two embryos at transfer? Hum Reprod 2005;20:1292–7.

Appendix: Health state descriptions are as follows:

• Can see normally • Is able to walk, and get around normally • Is occasionally fretful, angry, irritable, anxious, or

depressed • Learns and remembers very slowly and usually requires

special educational assistance • Eats, bathes, dresses, and uses the toilet normally for age.

Visual impairment You give birth to a child who: • Has difficulty seeing even with the use of glasses • Is able to walk and get around normally • Is generally happy and free from worry • Learns and remembers schoolwork normally for age • Eats, bathes, dresses, and uses the toilet normally for age.

Perinatal death with no subsequent pregnancy • Your infant dies around the time of birth. Afterwards, you

are unable to conceive again and live the rest of your life without ever giving birth to a child.

Premature delivery • Your child is born too early and has to be admitted to the

intensive care unit where they require 24-hours care and a special machine help them breath for several days. For several weeks after the birth, it is uncertain whether or not they will survive. If they were to survive, they would be at risk of developing long-term health problems as a result of being born too early.

Physical impairment

Giving birth to a healthy child (top anchor)

You give birth to a child who: • Can see normally • Requires special equipment to walk or get around independently • Is generally happy and free from worry • Learns and remembers schoolwork normally for age • Requires special equipment to eat, bathe, dress, or use the toilet independently.

You give birth to child who: • Can see normally • Is able to walk and get around normally • Is generally happy and free from worry • Learns and remembers schoolwork normally for age • Eats, bathes, dresses, and uses the toilet normally for age.

Cognitive impairment

• You develop severe pregnancy complications, and both you

You give birth to a child who:

Death for the mother and child during pregnancy (bottom anchor) and your child die during birth.


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