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

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.

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