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

Hum Reprod. 2006 Feb;21(2):344-51. doi: 10.1093/humrep/dei332. Epub 2005 Oct 20.

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.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Birth Rate
  • Embryo Transfer* / economics
  • Embryo Transfer* / psychology
  • Endpoint Determination
  • Female
  • Fertilization in Vitro / economics
  • Fertilization in Vitro / methods*
  • Fertilization in Vitro / psychology
  • Health Care Costs
  • Humans
  • Infertility, Female / therapy*
  • Live Birth* / economics
  • Ovulation Induction / economics
  • Ovulation Induction / methods*
  • Ovulation Induction / psychology
  • Pregnancy
  • Randomized Controlled Trials as Topic / methods*