Abstract from ESHRE 2003 in Madrid

USE OF GANIRELIX FOR RAPID DOWN-REGULATION BEFORE IVF TREATMENT – A NORDIC MULTI-CENTER TRIAL.

Lars Nilsson, Anders Nyboe Andersen, Svend Lindenberg, Jon Hausken.

The IVF-units of Sahlgrenska University Hospital, Goteborg, Sweden, Rigshospitalet and Herlevs Sygehus, Denmark, and Haugesunds hospital, Norway.

Background: 
Earlier pilot studies have indicated that GnRH antagonists might be used for rapid “down regulation” instead of 2-3 weeks of agonist treatment. This approach may show advantages for poor responders, since a flare up effect may be created.

Objectives: 
To induce luteolysis (primary endpoint) in 90 % of the patients within 7 days of treatment with 0.25 mg of ganirelix sc daily, and to achieve an acceptable pregnancy rate in a poor responder subsample.

Study design: 
Multicenter, extended pilot study, open.

Material and Methods: 
60 cycles in 60 patients, undergoing IVF or ICSI treatment in their second or third attempt, where the previous cycle had demonstrated a reduced response to gonadotrophin stimulation, using the long agonist protocol, defined as 4 or less oocytes harvested after a total FSH-dose of at least 2 000 IU and a starting dose of at least 150 IU of FSH. The women should be under 40 years, have a BMI below 35 and have a menstrual cycle length between 23-35 days. Ganirelix was administered in a daily dose of 0.25 mg for up to 7 days, from 3-5 days before expected menses.

“Luteolysis” was defined as: absence of a corpus luteum, endometrial thickness of 5 mm or less and no follicles above 10 mm on ultrasound scan, and a serum estradiol below 0.20 nmol/L, plus menstrual-like bleeding. Stimulation should then commence using 300-400 IU of rec-FSH (Puregon). Ultrasound scanning and estradiol measurement should be performed from day 6 of stimulation, and daily doses of ganirelix 0.25 mg reinstituted, when one follicle of 14 mm was detected. Injection of hCG should be performed when at least one follicle exceeded 17 mm in diameter and follicle puncture performed within 38 hours thereafter.

Results: 
The interimistic results show that (up to May 2003) 38 patients have started ganirelix treatment in 3 centers, 36 fulfilled the criteria of luteolysis and 26 have had a transfer of 1-2 embyos. An additional patient, who was not down regulated until after 9 days reached transfer. So far, 5 positive pregnancy tests and 4 ongoing pregnancies have been recorded, but 4 more end results are not yet ready. One or two other centers may show results in August.

Conclusions: 
It can be concluded, although prematurely, that a high proportion (36 out of 38) of patients do reach “luteolysis” by the present criteria within 7 days of treatment with 0.25 mg ganirelix (median 4 days). The treatment may constitute a favourable alternative to 2-3 weeks of agonist treatment