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

Sponsor

Merck KGaA, Darmstadt, Germany (Industry)

Overall Status

Completed

CT.gov ID

NCT01109654

Collaborator

Merck Pte. Ltd., Singapore (Industry)

2,175

Enrollment

Location

Duration (Months)

80.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Cetrorelix acetate and Follitropin alfa

Detailed Description

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

Study Design

Study Type:

Observational

Actual Enrollment :

2175 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 [3 month]
Assessment of subjects age, weight, height, FSH and LH level prior to Gonal-f administration, concomitant treatment, infertility history and infertility treatment
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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