title: Comparison of different treatment strategies in IVF with cumulative live birth over a given period of time as the primary end-point: methodological considerations on a randomized controlled non-inferiority trial.
abstract: BACKGROUND
  We discuss methodological considerations related to a study in IVF, which compares the effectiveness, health economics and patient discomfort of two treatment strategies that differ in both ovarian stimulation and embryo transfer policies.
  
  
  METHODS
  This was a randomized controlled clinical trial in two large Dutch IVF centres. The tested treatment strategies are: mild ovarian stimulation [including gonadotrophin-releasing hormone (GnRH) antagonist co-treatment] together with the transfer of one embryo, versus conventional stimulation (with GnRH agonist long protocol co-treatment) and the transfer of two embryos. Outcome measures are: (i) pregnancies resulting in term live birth; (ii) total costs per term live birth; and (iii) patient stress/discomfort per started IVF treatment, over a 12 month period. Power considerations for this study were an overall cumulative live birth rate of 45% for the conventional treatment strategy, with non-inferiority of the mild treatment strategy defined as a live birth rate no more than 12.5% lower compared with the conventional study arm. For a power of 80% and alpha of 0.05, 400 subjects are required.
  
  
  RESULTS
  As planned, from February 2002 until February 2004, 410 patients were enrolled.
  
  
  CONCLUSIONS
  This effectiveness study applies an integrated medical, health economics and psychological approach with term live birth over a given period of time after starting IVF as the end-point. Complete and timely patient enrolment vindicates many of the design decisions.
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. m.eijkemans@erasmusmc.nl
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: E M E W
authors.initials: EM
authors.lastname: Heijnen
authors.forename: C
authors.initials: C
authors.lastname: de Klerk
authors.forename: J D F
authors.initials: JD
authors.lastname: Habbema
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D001723:Birth Rate; D004624:Embryo Transfer / Q000191:economics / Q000523:psychology; D023381:Endpoint Determination; D005260:Female; D005307:Fertilization in Vitro / Q000191:economics / Q000379:methods* / Q000523:psychology; D017048:Health Care Costs; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D050498:Live Birth / Q000191:economics; D010062:Ovulation Induction / Q000191:economics / Q000379:methods* / Q000523:psychology; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic / Q000379:methods*