Letters to the editor |
Randomized single versus double embryo transfer studies: obstetric and paediatric outcome and a cost-effectiveness analysis
1 Department of Medicine, School of Medicine, Cardiff University and 2 Health Outcomes Research, Cardiff Research Consortium, University Hospital of Wales, Heath Park, Cardiff, UK
3 To whom correspondence should be addressed at: Medicentre, University Hospital of Wales, Heath Park, Cardiff CF14 4UJ, United kingdom. E-mail: currie{at}cardiff.ac.uk
Sir,
We read with interest the study comparing single-embryo transfer (SET) versus double-embryo transfer (DET). Although the study-specific findings published by Ann Kjellberg and colleagues (Kjellberg et al., 2006
) appear to be robust and convincing, some methodological details need to be addressed, if only to further support the conclusions drawn by the authors.
Their protocol stated that patients should be treated according to ordinary routines, while individual costs were obtained from one centre. To calculate the costs of drugs used for all centres, costs of FSH were used. While rFSH was indeed administered to a subgroup of women, others received HMG-HP (Thurin et al., 2004). Therefore, the cost of the not-less-effective but much-less-expensive treatment with HMG-HP should have been considered in the analysis. This may have had a notable impact on the results of the analysis. Reduction in the relative impact of drugs, although applicable to both SET and DET, would make differences to the analysis because of the effect of changes in neonatal morbidity that would also favour SET. Moreover, a preliminary report from the MERIT study (Nyboe-Andersen et al., 2005) comparing HMG-HP with rFSH provides evidence of higher embryo quality and a higher implantation rate when only high-quality embryos are transferred. Only good-quality embryos were used in the study evaluated by Kjellberg and colleagues. If SET is to be favoured over DET by decision-makers, more treatment cycles are likely to be made available to subfertile women. This would suggest that the evidence-based choice of gonadotrophins will play an increasingly important role and should be addressed also from the SET versus DET perspective. If only fresh embryos were to be used, however, SET would most likely be less cost-effective than with frozen cycles, and it has not been established whether it would be favoured over DET. The choice of gonadotrophin would have even more bearing on the relative cost-effectiveness if only fresh embryos were used, which would require more stimulation cycles per birth.
The analysis also raises issues about the way society values the ‘production’ of children, and how we measure health benefits, considering some estimates of the willingness to pay to have a child in excess of £1 million (Neumann and Johannesson, 1994) and the so-called economic value of a child of Ä1.8 million (Granberg, 2005).
In cost-effectiveness analysis, from a drug reimbursement perspective, outcome is measured typically by a generic unitary scale called health-related utility. Utility values range from 0 (a health state equivalent to death) to 1 (a perfect health state). A negative value is possible implying a health state worse than death. Utility is then used in health economics to generate a metric called quality-adjusted life years (QALYs). Here in the Health Outcome Data Repository (HODaR, 2006), for example, we measure utility directly using the EQ5Dindex (Currie et al., 2005). Measuring health benefit in terms of utility is important in countries such as the UK where drugs are evaluated for their cost-effectiveness. If treatments do not meet notional thresholds of incremental cost-effectiveness (£20 000 per QALY in the UK), then they may not be reimbursed widely. It is our conjecture that in studies such as this by Kjellberg and colleagues, the time horizon for analysis should be extended by a number of years, say 10, and that the ‘benefit’ of the child should be included in the analysis, even just as sensitivity analysis, however controversial it may be. There is also likely to be a decrement in utility in women who do not subsequently have children and in those who are refused or cannot afford treatment.
In essence, this alternative approach would not have resulted in a change in their conclusions, where SET appeared to be preferential over DET; a longer time horizon would most likely favour SET even more. What it would do is to raise awareness of the conclusion we would like to draw wider attention to; that if one includes the value of the resulting children, IVF is extremely desirable from a societal perspective because its incremental cost utility ratio (ICER) would be very low by comparison with other health interventions. Furthermore, that people value IVF treatment even if it is unsuccessful (Ryan, 1996) and that it should be funded, even encouraged, by state health services and other health paying agencies for people who require this form of assisted reproduction.
We raise one final issue. In this study, DET produced 60 more babies than did SET. It is possible that if a revised QALY estimate was calculated using total births—and it could be argued that you could calculate benefit in discounted lifetime QALYs for these births, rather than restrict it to only 10 years as we have suggested above—it might actually change their overall conclusion. Purchasers and clinicians are thought to prefer ‘birth events’ i.e. n = 1 if the birth involves either a single, twin or triple birth. If all babies were counted equally, DET could possibly produce much higher net benefit from a societal perspective.
References
Currie CJ, McEwan P, Peters JR, Patel TC, Dixon S. (2005) The routine collation of health outcomes data from hospital treated subjects in the Health Outcomes Data Repository (HODaR): descriptive analysis from the first 20,000 subjects. Value Health 8:581–590.[Medline]
Granberg M. (2005) Infertility treatment and health economics. Abstracts of the iCSi Conference, Copenhagen, 17th June 2005 (http://www.icsi.ws/information/abstracts_copenhagen_2005/infertility_treatment_and_health_economics2). Accessed 12 January 2006.
HODaR. Health Outcomes Data Repository. (2006) January 12, (www.hodar.co.uk). Accessed.
Kjellberg AT, Carlsson P, Bergh C. (2006) Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis. Human Reprod 21:210–216.
Neumann PJ and Johannesson M. (1994) The willingness to pay for in vitro fertilization: a pilot study using contingent valuation. Med Care 32:686–699.[CrossRef][Web of Science][Medline]
Nyboe-Andersen A, Devroey P, Arce J-C. (2005) A randomised trial (MERIT) comparing highly purified menotrophin and recombinant FSH in IVF. Abstracts of the 21st Annual Meeting of the ESHRE, Copenhagen, Denmark, p. i19 for the MERIT (Menotrophin vs Recombinant FSH in vitro Fertilisation Trial) Group (O-054).
Ryan M. (1996) Using willingness to pay to assess the benefits of assisted reproductive techniques. Health Econ 5:543–558.[CrossRef][Web of Science][Medline]
Thurin A, Hausken J, Hillensjo T, Jablonowska B, Pinborg A, Strandell A, Bergh C. (2004) Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med 351:2392–2402.
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