Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

Madelon van Wely, Irene Kwan, Anna L Burt, Jane Thomas, Andy Vail, Fulco Van der Veen, Hesham G Al-Inany, Madelon van Wely, Irene Kwan, Anna L Burt, Jane Thomas, Andy Vail, Fulco Van der Veen, Hesham G Al-Inany

Abstract

Background: Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review is to bring together all randomised studies in this field under common inclusion criteria with consistent and valid statistical methods.

Objectives: To compare the effectiveness of recombinant gonadotrophin (rFSH) with the three main types of urinary gonadotrophins (i.e. HMG, FSH-P and FSH-HP) for ovarian stimulation in women undergoing IVF or ICSI treatment cycles.

Search strategy: An extended search was done according to Cochrane guidelines including the Menstrual Disorders & Subfertility Group's Specialised Register of controlled trials, The Cochrane Central Register of Controlled Trials, MEDLINE (1966 to May 2010), EMBASE (1980 to May 2010), CINAHL (1982 to May 2010), National Research Register, and Current Controlled Trials.

Selection criteria: All randomised controlled trials reporting data comparing clinical outcomes for women undergoing IVF/ICSI cycles and using recombinant FSH in comparison with HMG or highly purified HMG, purified urinary FSH (FSH-P), and highly purified urinary FSH (FSH-HP) for ovarian hyperstimulation in IVF or ICSI cycles were included.

Data collection and analysis: Primary outcome measure was live birth rate and OHSS per randomised woman.Binary outcomes were analysed using odds ratios and also reported in absolute terms. Grouped analyses were carried out for all outcomes to explore whether relative effects differed due to key features of the trials.

Main results: We included 42 trials with a total of 9606 couples. Comparing rFSH to any of the other gonadotrophins irrespective of the down-regulation protocol used, did not result in any evidence of a statistically significant difference in live birth rate (28 trials, 7339 couples, odds ratio 0.97, 95% CI 0.87 to 1.08). This suggests that for a group with a 25% live birth rate using urinary gonadotrophins the rate would be between 22.5% and 26.5% using rFSH. There was also no evidence of a difference in the OHSS rate (32 trials, 7740 couples, OR 1.18, 95% CI 0.86 to 1.61). This means that for a group with 2% risk of OHSS using urinary gonadotrophins, the risk would be between 1.7% and 3.2% using rFSH.

Authors' conclusions: Clinical choice of gonadotrophin should depend on availability, convenience and costs. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety.