Multipledose

The two GnRH-nts (Cetrorelix or Ganirelix) were studied in order to achieve the best dose that blocks the premature LH rise and does not oversuppress the pituitary. Sommer et al. (16) were the first in describing the suppression of gonadotropin and estradiol secretion after 3 mg of Cetrorelix daily in normal cycling women. After that, the dose-finding studies generally initiated the gonadotropins (recombinant or urinary) on day 2 of menstrual cycle and the antagonist daily administration was initiated on stimulation day 6 (7-9,17). The risk for premature LH surge is higher after the sixth day of ovarian stimulation, and this day was chosen to initiate the antagonist injections (7). The authors of the different studies compared different doses of Cetrorelix or Ganirelix to achieve the best dose with most appropriate assisted reproductive technology (ART) results.

Comparing the Cetrorelix administration of three and 1 mg or 0.5 and 0.25 mg after day 6 of stimulation protocol, the authors showed that all patients had a decline on LH serum levels. The group of patients receiving 0.5 and 0.25mg/day showed the best ART results in terms of pregnancy and implantation rates without the risk of a pituitary oversuppression which occurred with one and 3mg (7,17). Another study compared the starting doses of 0.5, 0.25, and 0.1mg/day (8). The authors demonstrated that patients receiving 0.5 or 0.25 mg/day during the follicular phase did not showed premature LH surge, evidenced by the lower LH serum levels. However, one out of seven patients with 0.1 mg/day protocol showed a premature LH rise with progesterone elevation and the 0.1 mg dose was therefore abandoned. The results were similar between the patients receiving 0.25 and 0.5 mg/day in terms of clinical pregnancy and implantation rates.

The group of investigators concluded that the minimal necessary and effective dose to prevent premature LH surge was 0.25mg/day with Cetrorelix.

The Ganirelix Study Group (9) also investigated the minimal safe/ effective dose to achieve good IVF results. This study also showed that, during the multiple dose protocol with Ganirelix, the minimal effective dose was 0.25mg/day, inhibiting the premature LH secretion without compromising IVF results in stimulated cycles with recombinant FSH. This group of patients, receiving Ganirelix 0.25mg/day had the highest vital pregnancy rate per transfer (40.3%) as the main clinical outcome if compared with the others doses (0.0625-2mg).

Observing very low implantation rates in the groups of daily 1 or 2 mg, Kol et al. (18) analyzed the database from the Ganirelix dose-finding study (9) concerning the effect of GnRH-nt in freeze-thaw cycles. The authors concluded that high doses (1.0 and 2.0mg/day) of Ganirelix did not affect the biologic potential of embryos to develop clinical pregnancy.

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