Efficacy of Corifollitropin Alfa Versus Follitropin Beta in Aged IVF (In-vitro Fertilization) Patients
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 4

Summary: 
      A prospective, randomized, controlled study to explore the efficacy and safety of using
      either corifollitropin alfa 150 mcg or daily recombinant follicle stimulation hormone (FSH)
      300 international unit (IU) for the stimulation treatment of subjects undergoing controlled
      ovarian stimulation prior to IVF.

      The study is designed as a non-inferiority trial. The sample size for this trial of 400
      subjects, in both groups, being treated for one IVF cycle is based upon the primary endpoint
      of the number of oocytes retrieved.
    

Detailed description: 
      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.
    

Intervention name(s): corifollitropin alfa; Follitropin Beta
Intervention type(s): Drug; Drug
Intervention description(s): Drug is injected subcutaneously. Seven days after, 300 IU FSH daily injected subcutaneously, until at least two leading ovarian follicles reach 17mm in diameter.; Drug is injected subcutaneously, daily, until at least two leading ovarian follicles reach 17mm in diameter.
Other intervention name(s): Elonva; Puregon
Intervention MeSH terms: Follicle Stimulating Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment