title: Cost-effectiveness of embryo transfer strategies: a decision analytic model using long-term costs and consequences of singletons and multiples born as a consequence of IVF.
abstract: What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?
  
  
  
  From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained.
  
  
  
  According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated.
  
  
  
  A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women <38 years with a good quality embryo, and DET in all other women; and (v) three cycles of DET in all patients.
  
  
  
  Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed.
  
  
  
  With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively.
  
  
  
  This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation.
  
  
  
  The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members.
  
  
  
  This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article.
  
  
  
  Not applicable.
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands mirjam.van.heesch@mumc.nl.
authors.forename: M M J
authors.initials: MM
authors.lastname: van Heesch
authors.affiliation: Department of Pharmacy, University of Groningen, Deusinglaan 1, 9713 AV Groningen, The Netherlands.|Department of Epidemiology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: A D I
authors.initials: AD
authors.lastname: van Asselt
authors.affiliation: Department of Obstetrics and Gynecology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.|GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: J L H
authors.initials: JL
authors.lastname: Evers
authors.affiliation: Department of Neonatology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: M A H B M
authors.initials: MA
authors.lastname: van der Hoeven
authors.affiliation: Department of Obstetrics and Gynecology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.|GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: J C M
authors.initials: JC
authors.lastname: Dumoulin
authors.affiliation: Department of Biological Psychology, VU University, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
authors.forename: C E M
authors.initials: CE
authors.lastname: van Beijsterveldt
authors.affiliation: Department of Public Health, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.|Division of Woman and Baby, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Bonsel
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: R H M
authors.initials: RH
authors.lastname: Dykgraaf
authors.affiliation: Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands.|Department of Pediatrics, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: van Goudoever
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Koopman-Esseboom
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: W L D M
authors.initials: WL
authors.lastname: Nelen
authors.affiliation: Department of Neonatology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Steiner
authors.affiliation: Department of Neonatology, Emma Children's Hospital, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Tamminga
authors.affiliation: Academic Medical Center, Center of Reproductive Medicine, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Tonch
authors.affiliation: Department of Reproductive Medicine, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: H L
authors.initials: HL
authors.lastname: Torrance
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Dirksen
mesh_terms: D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D004624:Embryo Transfer / Q000191:economics* / Q000379:methods; D005260:Female; D005307:Fertilization in Vitro / Q000191:economics* / Q000379:methods; D006801:Humans; D018803:Models, Economic; D011247:Pregnancy; D018873:Pregnancy Rate; D011272:Pregnancy, Multiple; D019057:Quality-Adjusted Life Years; D012189:Retrospective Studies
keywords: assisted reproduction; child follow-up; cost-effectiveness; embryo transfer; multiple pregnancy