GnRH agonist versus antagonist therapy

I read with interest the article titled ‘Human ovarian steroid secretion in vivo: effects of GnRH agonist versus antagonist (cetrorelix)’ (Garcia-Velasco et al., 2001) and I got a little confused. The addition of four patients (two at the beginning of the study and two at the end) in order to have matching groups suggests that the study was a retrospective one. This is further supported by the fact that the subjects selected for this study were a subset of women enrolled in another phase III clinical study. There is no mention of this being a retrospective study, either in the Abstract or the text. Being retrospective can explain why two different regimens of FSH were used in both groups: step-down and fixed dose with gradual increments as needed. If it is really a retrospective study—using material obtained from subjects enrolled in another trial—then the conclusion reached by the authors would be markedly questionable (in view of the very limited sample size). Moreover, leuprolide acetate was given as 1 mg per day s.c. and the dose was adjusted according to the length of patient’s cycle in order to start the analogue 7 days prior to menstruation. In Table I it is confusing; the mean number of days of GnRH agonist was 12.2 while the mean total dose of GnRH agonist was 18.6 mg. The authors stated that, ‘If serum estradiol concentrations were beyond the cut-off point, the patient was excluded from the study’ and there is no mention of how many cases were excluded. Whether IVF was performed more than ICSI in the GnRH agonist-treated group is unclear from the data presented by the authors. Finally, the authors claimed a higher fertilization rate in the antagonist-treated group and this was the cornerstone of their conclusions. It is interesting that this was not the case in previous well designed, well conducted, randomized controlled trials comparing agonist versus antagonist (The European Orgalutran Study Group, 2000; the European Middle East Orgalutran Study Group, 2001).