An Efficacy and Safety Study of Corifollitropin Alfa Versus Daily Follitropin Beta for Controlled Ovarian Stimulation in Women 35-42 Years Old With a Body Weight ≥ 50 kg Undergoing IVF Treatment.

Stimulation regimen and assisted reproductive technology procedures Corifollitropin Alfa Group: On day 2 or day 3 of the menstrual cycle, a single subcutaneous injection of corifollitropin alfa 150 mg/ 0.5 mL is administered (stimulation day 1). FSH Group: Daily subcutaneous injections with recombinant FSH (Follitropin Beta) 300 international units (IU) is started on On day 2 or day 3 of the menstrual cycle (stimulation day 1) and continue up to and including stimulation day 7. From stimulation day 8 onwards, subjects from both treatment groups will continue with a daily subcutaneous dose of FSH up to the day before human chorionic gonadotropin (hCG) administration or gonadotropin releasing hormone agonist administration day. The maximum FSH dose to continue treatment after the first 7 days is 300 IU, but the dose could be reduced when desired. To prevent premature luteinizing hormone (LH) surges the gonadotropin releasing hormone (GnRH) antagonist (ganirelix acetate subcutaneous injection, 0.25 mg/ 0.5 mL) is administered, starting on stimulation day 5. As soon as at least three follicles of 17 mm are observed by ultrasound, hCG or a GnRH agonist will be used for final oocyte maturation at the same day. hCG is used if 3-18 follicles and 0.2 mg triptorelin is administered if ≥ 19 follicles >11 mm are observed. About 34-36 hours thereafter, oocyte retrieval followed by IVF or intra-cytoplasmic sperm injection (ICSI) is performed. Three days after oocyte pick-up, 2 to 3 fresh embryos will be transferred. If patients have high progesterone level on day of trigger (progesterone level > 1,5 ng/ml), risk of OHSS and unfavorable endometrium, fresh transfers will be cancelled and freeze all will be recommended. Patients using hCG for final oocyte maturation will receive luteal phase support with progestogen gel (90 mg once daily) intra-vaginally and estradiol (4 mg/day orally, twice daily) initiated on the day of oocyte retrieval or the day thereafter. Patients, using GnRH agonist for triggering, will have fresh transfer with intense luteal phase support of estradiol and progesterone (receive intense luteal phase support with estradiol and progesterone as the same dose mentioned above and progesterone 50 mg intramuscular injection per day). Assessments Patients will return to the clinic for pregnancy test 2 weeks after embryo transfers. Local tolerance parameters (pain, itching, swelling and redness) are assessed by the clinical staff 30 min after injection for both corifollitropin alfa and FSH injection sites. Clinical Outcome The primary objective is to show that the corifollitropin alfa regimen, in terms of the number of oocytes retrieved, is equivalent to the reference treatment (predefined equivalence range: -3 to +5 oocytes). Other clinical parameters will also be evaluated: dose of FSH required, duration of stimulation, number and size of follicles (≥11mm and ≥14 mm), serum hormone levels, fertilization rate, number and quality of embryos obtained, implantation rate, miscarriage rate, and pregnancy rates. At least 14 days after embryo transfer, a blood pregnancy test is performed. If the pregnancy test is positive, vaginal and/or abdominal ultrasonographic investigation is performed between 35 and 42 days ( 5 to 6 weeks) after embryo transfer to confirm a clinical pregnancy and at least 70 days (≥ 10 weeks) after embryo transfer to confirm an ongoing pregnancy. Patients will be followed to one year after randomization. All efficacy analyses will be based on the intent-to-treat (ITT) population, which included all randomized patients who will receive corifollitropin alfa or at least one dose of FSH Safety endpoints Occurrence of adverse events, including moderate and severe ovarian hyperstimulation syndrome (OHSS), outcome of local tolerance at injection site assessments will be evaluated as safety endpoints. The percentage of patients with moderate or severe OHSS and local tolerance is compared between the treatment groups using Fisher's exact test. Safety analyses will be performed on the all-subjects-treated group, which comprised all the patients who will receive either corifollitropin alfa or FSH.