PERgoveriS In Stratified Treatment for Assisted Reproductive Technique
Condition: Assisted Reproductive Techniques; Reproductive Technology, Assisted
Intervention: Gonal-f®; Pergoveris®; Pergoveris®; Recombinant human chorionic gonadotropin (r-hCG)
Intervention description: Gonal-f® (follitropin alfa) 300 International Unit (IU) will be administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5).; Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) administration day (at least 1 follicles >= 18 mm). The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.; Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.; 250 microgram of r-hCG will be administered once subcutaneously on r-hCG day (at least 1 follicles >= 18 mm).
Intervention MeSH terms: Chorionic Gonadotropin; Follicle Stimulating Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 202.0
Sex: Female
Minimum age: 36 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Ovulation Induction; Ovarian Stimulation; Reproductive Technique, Assisted; Assisted Reproductive Technics; Assisted Reproductive Technique; Reproductive Technology, Assisted

Summary:

      This is a multicenter, multi-national, randomized, open-label comparative trial. After
      screening, the subjects will start down-regulation treatment on Day 21-22 of the cycle.
      Down-regulation treatment will start within 2 months following the screening visit. The
      routine long luteal phase protocol for gonadotropin-releasing hormone (GnRH) agonist
      treatment will be followed. Once down-regulation has been confirmed, a pregnancy test will be
      performed just before randomization and start of recombinant human follicle-stimulating
      hormone (r-hFSH) treatment to rule out any pre-existing pregnancy. If the result is negative,
      the subject will be randomly assigned to one of the two treatment arms of the trial:

        -  GONAL-f®: (Liquid Pen; 300 international unit [IU] of per day) stimulation Day 1-5
           followed by Pergoveris® (vial/powder, 300 IU per day) from stimulation Day 6 and until
           required recombinant human chorionic hormone (r-hCG) criterion is met. The dose can be
           adjusted from stimulation Day 6 (increased or decreased) based upon the subject's
           ovarian response and according to the center's standard practice.

        -  Pergoveris®: (vial/powder, 300 IU per day) from stimulation Day 1 and until required
           r-hCG criterion is met. The dose can be adjusted from stimulation Day 6 (increased or
           decreased) based upon the subject's ovarian response and according to the center's
           standard practice.

      Randomization across the two treatment arms will be kept balanced in a 1:1 ratio. Follicular
      development will be monitored according to the center's standard practice by ultrasound (US)
      and/or estradiol (E2) levels, until the protocol r-hCG requirement is met (i.e., at least one
      follicle greater than or equal to [>=] 18 millimeter [mm] and two follicles >=16 mm). After
      this, a single injection of r-hCG will be administered in order to induce final oocyte
      maturation.

      At a time of 34-38 hours after r-hCG administration, oocytes will be recovered vaginally
      under US monitoring. Oocytes will then be fertilized in vitro and embryos replaced 2-5 days
      after oocyte recovery. Ovum pick up (OPU), in vitro fertilization (IVF), embryo transfer (ET)
      and luteal support will be performed as per center's standard practice.

      A post-treatment safety visit will be performed for all subjects who received r-hCG (pregnant
      and non- pregnant) on Day 15-20 post-hCG. For subjects who have withdrawn from treatment
      (i.e. after starting Pergoveris® or Gonal-f® but before hCG is given) this visit will take
      place 20-30 days after their first Pergoveris® or Gonal-f® treatment injection (excluding
      pregnancy testing).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be a female subject justifying an in vitro fertilization and embryo transfer (IVF/ET)
             treatment

          -  Be between her 36th and 40th birthday (both included) at the time of the randomization
             visit

          -  Have early follicular phase (Day 2-4) serum level of basal follicle stimulating
             hormone (FSH less than or equal to (=<)12 IU/L) measured in the center's local
             laboratory during the screening period (that is within 2 months prior to
             down-regulation start)

          -  A body mass index (BMI) less than (<) 30 kilogram per square meter (kg/m^2)

          -  Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length

          -  Be willing and able to comply with the protocol for the duration of the trial

          -  Have given written informed consent, prior to any trial-related procedure not part of
             normal medical care, with the understanding that consent may be withdrawn by the
             subject at any time without prejudice to her future medical care

          -  Have a male partner with semen analysis within the past 6 months prior to
             randomization considered adequate to proceed with regular insemination or
             intracytoplasmic sperm injection (ICSI) according to the center's standard practice.
             If these criteria are not met, the subject can only be entered if donor sperm will be
             used

          -  Other protocol specified inclusion criteria could also apply.

        Exclusion Criteria:

          -  Had >= 2 previous ART cycles with a poor response to gonadotrophin stimulation defined
             as =< 6 mature follicles and/or =<4 oocytes collected in any previous IVF cycle or
             previous cycles with a hyper response defined as >= 25 oocytes retrieved

          -  Any medical condition, which in the judgment of the investigator may interfere with
             the absorption, distribution, metabolism or excretion of the drug. In case of doubt,
             the subject in question should be discussed with Merck Serono's medical responsible

          -  Had previous severe ovarian Hyperstimulation Syndrome (OHSS)

          -  Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the
             occurrence of OHSS

          -  Any contraindication to being pregnant and/or carrying a pregnancy to term

          -  History of 3 or more miscarriages (early or late miscarriages) due to any cause

          -  A clinically significant systemic disease

          -  Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the
             trial subject or her male partner

          -  Known allergy or hypersensitivity to human gonadotrophin preparations

          -  Entered previously into this trial or simultaneous participation in another clinical
             trial.

          -  Pregnancy and lactation period

          -  Participation in another clinical trial within the past 30 days

          -  Other protocol specified inclusion criteria could also apply.