Cetrotide Treatment Optimization
Condition: In Vitro Fertilization; Intracytoplasmic Sperm Injection
Intervention: Cetrotide (Ovarian stimulation); Cetrotide (Ovarian stimulation)
Intervention description: Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2; Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.
Intervention MeSH terms: Cetrorelix
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 617.0
Sex: Female
Minimum age: 18 Years
Maximum age: 39 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cetrotide; IVF; ICSI; Treatment protocol

Summary:

      Rationale:

      In daily practice fertility treatment is increasingly patient focused and innovative
      medication and standardized treatment guidelines are being developed to improve patient
      convenience.

      GnRH antagonist cotreatment to prevent premature luteinization during ovarian stimulation for
      IVF and ICSI greatly reduces the burden of treatment, partly by reducing the number of
      injections by around 21 compared with the optimal GnRH agonist 'long' protocol. However, the
      optimal GnRH antagonist protocol is still not known. There are a number of reasons to suggest
      that both the simplicity of treatment and clinical outcomes could be further improved by
      commencing GnRH antagonist treatment on the same day on which ovarian stimulation is started.
      These include more synchronized follicle development and reduced rates of premature
      luteinization. This study will investigate whether a novel early fixed start protocol
      improves outcomes in comparison to the widely employed late fixed start protocol.

      Objective:

      To demonstrate whether an early fixed start antagonist protocol improves the live birth rate
      compared with a late fixed start antagonist protocol by 5%.

      Study design:

      Prospective, multicenter, investigator sponsored, randomized controlled trial

      Study population:

        -  Normo-ovulatory women < 39 years with an indication for IVF or ICSI

        -  No more than 2 previous unsuccessful IVF/ICSI cycles

        -  BMI ≤ 32 kg/m2

      Intervention:

      Two different GnRH antagonist treatment protocols used in daily practice will be compared.
      Patients will be randomized to receive one of the following two treatments:

        -  Early fixed start: start GnRH antagonist treatment with Cetrotide 0.25 mg on the same
           day as FSH, cycle day 2.

        -  Late fixed start: FSH will be administered from cycle day 2. GnRH antagonist treatment
           with Cetrotide 0.25 mg will commence on cycle day 6.

      Main study parameters/endpoints:

      The primary endpoint is the live birth rate per started cycle. A secondary endpoint is the
      number of embryos available for transfer.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      In addition to recording clinical outcomes, endocrine studies will be carried out at the UMC
      Utrecht in a sample of 200 participants who will be subjected to blood sampling at three
      points during the treatment cycle: prior to commencing treatment on cycle day 2, cycle day 6
      and the day of hCG administration.The aim of this substudy was therefore to prospectively
      compare the effect of a cycle day 2 versus cycle day 6 fixed start GnRH antagonist protocol
      on LH, estradiol and progesterone levels in the mid and late follicular phase. In order to
      investigate whether the early fixed protocol exerts a significant extra burden on patients
      compared to the late start protocol, another group of 200 participants at the UMCU will be
      requested to complete the HADS questionnaire (Hospital Anxiety and Depression Scale).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Normo-ovulatory women < 39 years with an indication for IVF or ICSI

        Exclusion Criteria:

          -  More than 2 previous unsuccessful IVF/ICSI cycles

          -  BMI > 32 kg/m2