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A single injection of long acting gnrh-antagonist -degarelix- downregulates hypophysis during ovarian stimulation. A randomized controlled trial

      Objective

      Study’s objective was to examine if the use of a novel long acting, single dose GnRH antagonist, Degarelix, can cause efficient pituitary downregulation during ovarian stimulation in oocyte donors.

       Design

      This RCT (Trial Registration Number: NCT03861715) recruited healthy young oocyte donors (<35yrs) between January 2017-January 2019 in Assisting Nature, Centre of Assisted Reproduction and Genetics, Thessaloniki, Greece. Two groups of patients were examined; the first group (study group) the received a single Day-6 follicular dose of degarelix (Firmagon, Ferring Pharmaceuticals); the second group (control group) received daily 0,25mg of ganirelix as is the standard antagonist protocol. Study Group (Degarelix group) consisted of 80 women, who followed the new protocol, whereas, 93 donors followed the classical fixed Day6 GnRH-antagonist protocol.

      Materials and methods

      Ovarian stimulation was initiated on cycle Day2 or 3 with gonadotropins 225 IU (200-300), daily, in both groups. In Control group 0.25 mg of antagonist ganirelix was administered daily from stimulation Day6 in a fixed manner. In the new study group, on the same day, day-6, a single bolus injection of 0.1 ml Degarelix was administrated subcutaneously. Agonist triggering (Triptorelin 0.3ml) was employed for all and OPU performed at 36h. Fresh or frozen blastocyst-only transfer was performed following recipient endometrial estrogen and progesterone priming.

      Results

      No LH rise or any OHSS was noticed in any groups. Mean age (27.1 vs 27.9 years), mean AMH (4.1 vs. 3.6ng/ml) and total gonadotropin dose (2400 vs 2508 IU) of participants were not different among Control-group- and Study-group respectively. Similar number of oocytes retrieved (18.1 vs.17.1, p>0.05) with degarelix short antagonist group, and similar number of blastocysts produced in both groups (6.6 in Control-group-A vs. 6.9 in Study-group). All recipients underwent 2 blastocysts transfer. Pregnancy is expressed per donor. Initial positive HCG per donor was significantly higher (p<0.05) in the Degarelix Short Antagonist (Study-Group) 78.7% (63/80) as compared with 65.5% (n=61/93) in classic short antagonist (Control-Group). Cumulative delivery rate was higher 60.0% (48/80) in the new single shot Degarelix short antagonist group as compared to 50.5% (n=47/93) in classic antagonist group, however not significant (p>0.05).

      Conclusions

      The new long-acting GnRH antagonist in a single bolus dose of 0,1 mg carries no risk for LH, produce mature oocytes and achieve comparable pregnancy outcome to the classical short multiple dose antagonist protocol. This new protocol is first described by us, it is more patient friendly decreasing the number of injections that a patient receives. This is an ongoing study, dose of degarelix was arbitrarily chosen by our team, and more degarelix doses can be tested in future studies.