GnRH antagonist in assisted reproduction: a Cochrane review

In the present systematic review, we wished to compare the efficacy of gonadotrophin-releasing hormone (GnRH) antagonist and GnRH agonist administration for controlled ovarian hyperstimulation in assisted conception.

Five randomized controlled trials fulfilled the inclusion criteria. In four studies, the multiple low-dose (0.25 mg) antagonist regimen was applied and, in one study, the single high-dose (3 mg) antagonist regimen was investigated. In all trials, reference treatment included a long protocol of GnRH agonist (buserelin, leuprorelin or triptorelin) starting in the mid-luteal phase of the preceding cycle.

In comparison with the long protocol of GnRH agonist, the overall odds ratio for the prevention of premature LH surges was 1.76 [95% confidence interval (CI) 0.75-4.16], which was not statistically significant. There were significantly fewer clinical pregnancies in those treated with GnRH antagonists (OR 0.79; 95% CI 0.63-0.99). There was no statistically significant reduction in incidence of severe ovarian hyperstimulation syndrome between the two regimens (relative risk 0.51; OR 0.79; 95% CI 0.22-1.18).

We concluded that the fixed GnRH antagonist protocol is a short and simple protocol with good clinical outcome, but the lower pregnancy rate compared with the GnRH agonist long protocol and the non-significant difference between both protocols regarding prevention of premature LH surge and prevention of severe ovarian hyperstimulation syndrome necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist. The clinical outcome may be further improved by developing more flexible antagonist regimens, taking into account individual patient characteristics.