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Reply: Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis
Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Gothenburg, Sweden
1 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, S-413-45 Gothenburg, Sweden. E-mail: christina.bergh{at}vgregion.se
Sir,
We thank Dr Currie and Dr Wechowski for their interest in our article ‘Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis’ (Kjellberg et al., 2006
) by Ann Thurin Kjellberg, Per Carlsson and Christina Bergh.
- The first comment concerns the choice of gonadotrophin and the costs for drugs. It is correct that in the present multicentre study, costs were generally obtained from one centre. To calculate the costs of drugs used for all centres, costs of rFSH were used, despite the fact that also HMG-HP was used for some cycles. However, during the period of randomization to the single-embryo transfer (SET) study, years 2000–2003, there was no registered HMG drug available in Sweden. One clinic in Denmark used HMG-HP (Menopur, Ferring) in the treatment of 14 patients. These cycles represent 2% of all the treatments, and we considered it reasonable to disregard the lower costs in the present analysis. In all other treatments in the study, rFSH was used.
Several sensitivity analyses were performed in this study, and of course an additional sensitivity analysis could be performed where rFSH is changed to HMG-HP. HMG-HP has been found to give similar (Van Wely et al., 2003) or at least as high (Nyboe Andersen et al., 2005) ongoing pregnancy rates as rFSH. Since the costs are lower for HMG-HP, a change from rFSH to HMG-HP should favour the SET group. Such a change would affect the SET group more since more cycles, but at a lower price, are needed in the SET group to achieve a similar number of deliveries as in the DET group.
- The second comment concerns the costs in the two groups if only fresh cycles had been included and compared. Such an analysis could of course easily be done if requested. However, the overall aim of the present study was to compare eSET, including one frozen/thawed cycle if no delivery in the fresh cycle, with DET (Thurin et al., 2004). We regard such a comparison more relevant than comparing eSET-only fresh cycle with DET as the objective was to maximize the number of deliveries and minimize risks for babies and mothers. Therefore, both groups have two embryos at the beginning, in the eSET group one transfer one embryo at a time, while in the DET group both embryos are transferred at one time point. We think, both for decision-makers and others, it is important to encourage the use of frozen cycles; in Sweden and the other Nordic countries, the number of frozen/thawed cycles is increasing steadily and are in some units already exceeding the number of fresh cycles.
- We are aware of studies presenting the ‘production’ costs of children (Neumann and Johannesson, 1994; Granberg, 2005) and found the results thought provoking. We have discussed the costs for IVF put in a broader health policy context in the ‘Discussion’ in our paper without referring to the two studies. One reason is that these calculations and the interpretation of the policy implications are not uncontroversial. The limitation of public-financed IVF as is done in most countries includes other considerations besides the cost–benefit aspects.
- An extended analysis of our data is proposed by the authors. A model analysis with an extended time horizon to calculate costs per quality-adjusted life years (QALYs) gained has been discussed in our group. However, despite the near universal outcome, cost-utility analysis has been considered to have little relevance to the management of infertility where lives are produced and not saved (Collins, 2002). In addition, severe disabilities as well as having no child would be difficult to characterize and measure. How should one calculate the utility of getting a child with severe disability? Even if long-term costs for these children would be possible to calculate, the calculation of utility will be a challenge. One could argue that all children have the same value, regardless of severe disability or not, while others might disagree. It should be pointed out that the primary efficacy outcome for this study, live birth, was chosen also from this perspective. We considered it of limited controversy to exclude stillborn babies. All other live born babies were included as ‘success’, also a few babies who died a few days after delivery (all in the DET group). This is of course a simplification of an extremely difficult problem. We agree with the authors, this alternative approach would not have changed our conclusion.
- The last issue brought up by Currie and Wechowski concerns how SET would compare with DET if analysing lifetime QALYs and calculating all babies equally. This is probably a more sensitive approach. If 60 more children born in the DET group are included in the analysis with equal value, the conclusion from our study would probably be different. However, if extending the analysis to lifetime QALYs, we are not sure this would favour DET. It is known that the lifetime costs for children with severe disabilities are very high (CDC, 2004). Moreover, we believe that not only purchasers and clinicians but also most parents prefer ‘birth events’.
References
CDC (Centers for Disease control and prevention). (2004) Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment—United States. MMWR Morb Mortal Wkly Rep 53:57–59.[Medline]
Collins JA. (2002) An international survey of the health economics of IVF and ICSI. Hum Reprod Update 8:265–277.
Granberg M. (2005) Infertility treatment and health economics. Hum Reprod 20:Suppl. 1, i101.
Kjellberg AT, Carlsson P, Bergh C. (2006) Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis. Hum 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. for the MERIT (Menotrophin vs Recombinant FSH in vitro Fertilisation Trial) group. (2005) A randomised trial (MERIT) comparing highly purified menotrophin and recombinant FSH in IVF. Hum Reprod 20:Suppl. 1, i19.
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.
Van Wely M, Westergaard LG, Bossuyt PM, Van der Veen F. (2003) Human menopausal gonadotropin versus recombinant follicle stimulating hormone for ovarian stimulation in assisted reproductive cycles. Cochrane Database Syst Rev 1:CD003973.[Medline]
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