Cetrorelix and Ganirelix Flexible Protocol for (IVF)

Study Overview
=================
Brief Summary
-----------------
Recombinant gonadotropins are currently used for ovarian stimulation in women undergoing to IVF for infertility. Recently new flexible protocols have been introduced: the single dose and multiple dose protocol. The single dose protocol is performed just using Cetrorelix by the administration of a single injection of Cetrorelix 3 mg subcutaneous when the lead follicle is ≥ 14 mm. The multiple dose protocol consider the daily administration of Cetrorelix 0.25 mg subcutaneous or Ganirelix 0.25 mg subcutaneous when the lead follicle is ≥ 14 mm and until the realization of hCG criteriaThere are few data from letterature about the comparison of the efficacy in pitituary suppression and pregnancy outcome of Ganirelix and Cetrorelix. Objective: to compare the efficacy in pituitary gonadotropin suppression and IVF outcome of multiple dose flexible gonadotrophin-releasing hormone (GnRH) antagonist administration according to follicular size using daily injection of Cetrorelix or Ganirelix. Interventions : patients are randomly assigned in to Cetrorelix acetate group or Ganirelix acetate group. Multiple dose of Cetrorelix acetate (0.25 mg) or multiple dose of Ganirelix acetate (0.25mg) are administered when the lead follicle is ≥ 14 mm until hCG criteria are met.Oocyte maturation trigger is performed by the administration of subcutaneous r-hCG (250 μg) or of intramuscular hCG (10,000 IU). After 36 hour transvaginal oocyte retrieval is performed followed by ICSI and embrio transfer (72 hours later).

Official Title
-----------------
Cetrorelix and Ganirelix Flexible Protocol for In Vitro Fertilization: a Prospective Randomized Trial

Conditions
-----------------
Infertility/Sterility

Intervention / Treatment
-----------------
* Drug: Ganirelix Acetate
* Drug: Cetrorelix Acetate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : 18-39 hyears old with regular menstrual cycles (25-35 days in length); Body Mass Index between 18-29 kg\m2 Basal follicle-stimulating hormone levels within normal range (<30 mUI\mL) Absence of clinically relevant anomalies at transvaginal ultrasound examinatio Exclusion Criteria: Patients affected by grade III or IV endometriosis according to American Society for Reproductive Medicine (ASRM) History of Ovarian Hyperstimulation Stimulation (OHSS) History of poor response in previous IVF\ICSI cycle: ≤ 3 oocytes retrieved ≥ 3 prior consecutive IVF\ICSI cycle without a clinical pregnancy.

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: ganirelix<br>multiple dose of Ganirelix acetate (0.25mg) are administered when the lead follicle is ≥ 14 mm until hCG criteria are met | Drug: Ganirelix Acetate<br>* multiple dose of Ganirelix acetate (0.25mg) are administered when the lead follicle is ≥ 14 mm until hCG criteria are met<br>|
| Experimental: cetrorelix<br>multiple dose of Cetrorelix acetate (0.25mg) are administered when the lead follicle is ≥ 14 mm until hCG criteria are met | Drug: Cetrorelix Acetate<br>* multiple dose of Cetrorelix acetate (0.25mg) are administered when the lead follicle is ≥ 14 mm until hCG criteria are met<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum LH levels | percentage of patients not having serum levels of LH ≥ 10IU\L (defined as premature LH surge) on the day of hCG administration. | through study completion,an average of 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of follicles ≥ 14mm on the day of hCG administration | number of follicles ≥ 14mm | through study completion,an average of 9 months | 
| FSH serum levels on the day of hCG administration | mUI/ml | through study completion,an average of 9 months | 
| FSH on the day of antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| FSH serum level on the day after the antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| LH serum level on the day of antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| LH serum level on the day after the antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| E2 serum level on the day of antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| E2 serum level on the day after the antagonist administration | mUI/ml | through study completion,an average of 9 months | 
| number of oocyte retrieved | how many oocyte were retrieved on transvaginal oocyte retrieval | through study completion,an average of 9 months | 
| number of metaphase II oocyte retrieved | how many metaphase II oocyte were retrieved on transvaginal oocyte retrieval | through study completion,an average of 9 months | 
| embryos obtained for patients | how many embryos were obtained for patient for each arm | 72 hours after transvaginal oocyte retrieval | 
| grade A embryos transferred | number of grade A embryo were transferred for patient | 72 hours after transvaginal oocyte retrieval | 
| total dose of gonadotropins administered | number of Units of gonadotropin administered for Controlled Ovarian Hyperstimulation | through study completion,an average of 9 months | 
| duration of gonadotropin treatment | how many days were necessary to complete the Controlled Ovarian Hyperstimulation | through study completion,an average of 9 months | 
| percentage of patients developing OHSS | how many patient for each arm develop OHSS (Ovarian Hyperstimulation Syndrome) | 15 days after the transvaginal oocyte retrieval | 
| implantation rate | The number of gestational sacs observed divided by the number of embryos transferred. | 30 days after the embyo transfer | 
| pregnancy rate | The number of clinical pregnancy (Positive hCG test) divided by the number of embryos transferred | 14 days after the transvaginal oocyte retrieval | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
In vitro fertilization, gnrh antagonist, pituitary suppression