Optimizing GnRH antagonist administration: A meta-analaysis of fixed vs flexible protocol

Abstract

The most commonly used method for administration of the antagonist is on a daily dose of 0.25 mg starting on a fixed day (day 6 of gonadotrophin stimulation). As there are individual variations in patient response to ovarian stimulation, then a starting GnRH antagonist according to follicular size (flexible protocol) could be of value. The aim is to investigate whether flexible GnRH antagonist administration according to follicular size would be more beneficial than starting it in a fixed day. Meta-analysis of randomized controlled trials A comprehensive search strategy was applied including searching Cochrane Menstrual Disorders and Subfertility Review Group specialized register, MEDLINE and EMBASE databases, Hand searching the reference lists of included studies, review and relevant textbooks and abstracts of major international meetings. Only randomised controlled trials in which subfertile couples undergoing ovulation induction using GnRH antagonist as part of an assisted reproductive cycle were included. The data combined for meta-analysis with RevMan software (using the Mantel-Haenszel method). Outcomes: Primary outcomes included pregnancy rate (per woman or per couple) and incidence of premature LH surge. Secondary outcomes included number of oocytes retrieved, amount of antagonist ampoules used, amount of gonadotrophins needed Seven trials were identified (Ludwig et al, 2001, Mansour et al, 2002, Othman et al, 2003, Klipesten et al, 2003, Mochtaret al, 2003 and Escudero et al, 2004.) Only three RCT met out inclusion criteria (Ludwig et al, 2001, Mochtar et al, 2003 and Escudero et al, 2004) enrolling 373 participants. There was no statistically significant difference in pregnancy rate per woman randomized O.R 0.7 (95% CI 0.45–1.1). There was no premature LH surge in any participants in both protocols. However, there was statistically significant reduction both in number of antagonist ampoules and amount of gonadotrophins used in the flexible protocol (O.R -1.2 95% CI -1.26–-1.15). There was a trend to an increase in the number of oocytes retrieved with the flexible protocol (OR 1.28 95% CI 0.9–1.6). The flexible protocol yields similar pregnancy rate as the fixed protocol but is more cost effective. However, further studies with large sample size and adequate power are needed.