Ganirelix

All patients were treated with GnRH antagonist protocol, as part of the COS of IVF treatment. Gonadotrophins (Gonal- F®; Serono, Hellas) were administered from day- 2 of the cycle, if the hormonal levels were basal. The initial dose of the gonadotrophins was predefined at 150- 300 IU for all patients and remained fixed for 5 days. After this period, the dose could be adjusted to each patient, according to the follicular growth and the estradiol levels.
Co- treatment with GnRH antagonist started on Day 6 of the stimulation with 0.25 mg cetrorelix (Merck-Serono) or 0.25 mg ganirelix (MSD).
The final oocyte maturation was induced when at least 3 follicles of 18 mm were present during ultrasound examination. Oocyte retrieval was performed 36 h after the administration of the triggering regimen. When <14 follicles were present, rec-HCG (Ovitrelle®; Merck-Serono) was administered. Alternatively, if ≥14 follicles were present, then agonist triggering was chosen with 0.3 mg Triptorelin (Arvekap®, IPSEN).

During IVF trials, stimulation is achieved with 100 to 300 IU of gonadotrophins depending on age, body mass index (BMI) and the Anti-Mullerian hormone (AMH) level (FSHrec: Puregon,; MSD, Oss, the Netherlands; GonalF: Merck-Serono, Geneva, Switzerland) or human Menopausal Gonadotrophin (Menopur, Ferring, Alost, Belgique). Ovulation was controlled by either gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix, Merck Serono or Ganirelix, MSD) or GnRH agonist (Buserelin: Suprefact; Sanofi-Avantis, Diegem, Belgium or triptoréline: Gonapeptyl, Ferring) respectively in 68% (170 cycles) and 32% (81 cycles) of cases. The GnRH antagonist is administered according to a flexible protocol which is once daily, when at least one follicle has reached a diameter of 14 mm and / or the oestradiol (E2) level is at 400 pg / ml. When a GnHR agonist is used, the long protocol is applied in the majority of such cycles. Triggering was obtained with 5000 IU of human chorionic gonadotrophin (hCG) (Pregnyl, MSD, Bruxelles, Belgium).

The long GnRH-agonist protocol (n = 2299 cycles) was accomplished by administering 600 μg intranasal Buserelin (Suprefact, Hoechst, Germany) from the mid-luteal phase of the preceding cycle in order to obtain pituitary functional suppression. In the GnRH-antagonist protocol (n = 1054 cycles), ganirelix (Orgalutran, MSD, Readington, NJ, USA) was administered (0.25 mg/d s.c.) from stimulation day 5, according to a fixed regimen. Either the recombinant FSH (rFSH; Gonal F, Merck, Darmstadt, Germany or Puregon, MSD, Readington, NJ, USA), or the human menopausal gonadotropin (hMG; Meropur, Ferring, Germany) was administered in order to stimulate multiple follicular growth. The gonadotropin starting dose (100–375 IU) was individually chosen according to the age, BMI, circulating AMH, and antral follicle count (AFC), and was then adjusted from stimulation day 5–7 according to the ovarian response at the first checkpoint, during which the transvaginal US (TV-US) plus the serum estradiol (E2) measurement were performed. The follicular growth was then monitored by the TV-US plus serum E2 every 2–3 days, and when the leading follicle reached 17–18 mm diameter, with appropriate E2 circulating levels, ovulation was triggered by a single subcutaneous injection of 10,000 IU hCG (Gonasi HP, Ibsa, Lugano, Switzerland).