Cetrotide Treatment Optimization

Study Overview
=================
Brief 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).

Official Title
-----------------
Prospective, Multicenter,Randomized Controlled Trial Towards Identifying the Optimal GnRH Antagonist Treatment Protocol

Conditions
-----------------
In Vitro Fertilization, Intracytoplasmic Sperm Injection

Intervention / Treatment
-----------------
* Drug: Cetrotide (Ovarian stimulation)
* Drug: Cetrotide (Ovarian stimulation)


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD2<br>Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins. | Drug: Cetrotide (Ovarian stimulation)<br>* Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2<br>* Other names: Cetrorelix;|
| Experimental: CD6<br>Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2. | Drug: Cetrotide (Ovarian stimulation)<br>* Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.<br>* Other names: Cetrorelix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Ongoing Pregnancy Rate |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cetrotide, IVF, ICSI, Treatment protocol