Pituitary sensitizing effect of GnRH antagonists: a mechanism explaining LH escape during IVF?

Background: GnRH antagonists have been introduced to induce persistent LH suppression. Many studies show a gradual increase of LH levels after several days of GnRH antagonist administration, the so-called escape or rebound effect. We hypothesize that, under chronic GnRH antagonist administration, a higher pituitary response to GnRH could be an underlying mechanism explaining the escape phenomenon. Methods: In a prospective study, pituitary response to a supramaximal test dose of GnRH was tested in 12 post-menopausal women before and 8 days after daily treatment with 0.5 mg GnRH antagonist (ganirelix). The same strategy was applied, after a wash-out period, in 11 of the same women using daily 0.5 mg GnRH antagonist in combination with daily estradiol (E-2, 50 mu g) administration. The main outcome measure was the LH response 30 min after GnRH administration (Delta LH 30) after the various GnRH tests. Results: The Delta LH 30 increased significantly after antagonist administration [Median (range): from 65.5 (32-85) to 77.5 (47-122) IU/l; P = 0.002]. During E-2 administration, the LH response to the GnRH test did not change significantly. Conclusions: Pituitary response increases after 8 days of GnRH antagonist administration. An escape/rebound phenomenon may result from increased pituitary response to endogenous GnRH.