An Observational Study of Cetrotide® Gonadotropin-releasing Hormone Antagonist (GnRH Antagonist) With GONAL-f® in Assisted Reproductive Technologies (ART)

Study Overview
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Brief Summary
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This is a multicentric, prospective, observational study on the use of Cetrotide to control the endogenous gonadotrophin levels in Gonal-f stimulated ART treatment cycles in the Asia-Pacific region. The study plans to enrol approximately 1800-2000 subjects over a 9-month period at each participating centre. This observational study is initiated to collect information on the use of Cetrotide (GnRH antagonist) in ART cycles in routine practice across the Asia-Pacific region. The information will allow a better understanding of the current ovarian stimulation regimens that involve Cetrotide in the control of the endogenous gonadotrophin concentrations. The collection of live birth data, though a challenging task, as a secondary endpoint will allow the study to show valuable information on the final objective of ART. To minimize the potential variability due to the different ovarian stimulation agents, the study is to include cycles treated with Gonal-f (recombinant human FSH) since this agent is widely available in the region.

Detailed Description
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Gonadotrophin-releasing hormone (GnRH) antagonists were introduced in the beginning of this decade for the use in ART. The potential advantages of GnRH antagonists over the GnRH agonists include the avoidance of an acute stimulation of endogenous gonadotrophins and a dramatic reduction in the length of analogue treatment. Despite the plus points of GnRH antagonists in ART, there has been some concern over the lower pregnancy rate reported, which may be the cause of a lower acceptance of GnRH antagonists in ovarian stimulation for in vitro fertilization (IVF). Interestingly, a separate meta-analysis did not reach the same finding. The probability of live birth after ovarian stimulation for IVF was found not to be dependent on the type of analogue used for pituitary suppression Cetrotide, a GnRH antagonist from Merck Serono, is currently approved for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation in majority of the regions. It is given either as a single-dose regimen of 3 mg injection or as a multiple-dose regimen of 0.25 mg daily injection. Both regimens have been shown to offer equivalent efficacy and safety outcomes. OBJECTIVES: Primary objective: To assess the effectiveness of Cetrotide regimens, when used with Gonal-f, in routine ART treatment cycles Secondary objectives: To assess the effectiveness of Cetrotide regimens on other efficacy endpoints To survey the types of Cetrotide regimen used and their success rates To assess the safety of Cetrotide regimens To explore the association between subject characteristics and treatment outcomes

Official Title
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A Prospective, Observational Study on the Use of Cetrotide (GnRH Antagonist) With GONAL-f in Assisted Reproductive Technologies (ART)

Conditions
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Infertility

Intervention / Treatment
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* Drug: Cetrorelix acetate and Follitropin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are undergoing ovarian stimulation for IVF or ICSI therapy Decision by treating physician to prescribe Gonal-f for controlled ovarian stimulation prior to study enrolment Decision by treating physician to prescribe Cetrotide as the down-regulation agent prior to study enrolment Exclusion Criteria: Subjects using GnRH agonist as the down-regulation agent Contraindicated use of Cetrotide based on local label Subjects who have participated in the study previously Subjects with hypersensitivity to cetrorelix acetate, extrinsic peptide hormones or mannitol Subjects with known hypersensitivity to GnRH or any other GnRH analogs Subjects with known or suspected pregnancy, and lactation
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cetrorelix acetate and Follitropin alfa|Cetrorelix acetate given either as a single-dose regimen of 3 mg injection or as a multiple-dose regimen of 0.25 mg daily injection.Ovarian stimulation therapy with Follitropin alfa generally starts on cycle Day 2 or 3. The starting dose of Follitropin alfa is based on the Investigators' discretion|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving a clinical pregnancy. | A transvaginal ultrasound scan will be performed on all subjects who become pregnant provided that no miscarriage has occurred. | At post hCG days 35-42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with cancelled cycles |  | 3 month | 
| Proportion of women with OHSS or risk of OHSS |  | 3 month | 
| Duration and dose of Cetrotide administered |  | 3 month | 
| Assessment of baseline characteristics | Assessment of subjects age, weight, height, FSH and LH level prior to Gonal-f administration, concomitant treatment, infertility history and infertility treatment | 3 month | 
| Total dose of Gonal-f administered |  | 3 month | 
| Duration of ovarian stimulation |  | 3 month | 
| Number of oocytes retrieved |  | 3 month | 
| Number of subjects with Adverse Events |  | 3 month | 
| Pregnancy rate |  | 12 month | 
| Live birth rate |  | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fertilization in Vitro, Reproductive Techniques, Assisted, Follicle Stimulating Hormone, Cetrotide, Gonal-f