Gonadotropin-releasing Hormone Antagonist on Triggering Day: A Randomized Controlled Study

Study on the Effect of GnRH Antagonist on hCG Day on Outcomes of Controlled Ovarian Hyperstimulation With GnRH Antagonist Flexible Multiple-dose Protocols

Gonadotropin-releasing hormone (GnRH) antagonists have been widely used for the prevention of premature luteinizing hormone (LH) surges during controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) since the late 1990's.

Many years have passed since GnRH antagonists were introduced to prevent premature LH surges during stimulated cycles. However, there is still no consensus on the optimal GnRH antagonist protocol. Attempts at modifying GnRH antagonist protocols have been made to improve COH outcomes. However, a meta-analysis of 27 randomized controlled trials, including recent reports, showed significantly lower clinical ongoing pregnancy rates in the antagonist group. Thus, additional efforts are needed to identify the optimal stimulation protocols to achieve better follicular and embryonic development and to improve the pregnancy rates in COH using GnRH antagonist.

Given the assumption of a detrimental effect of GnRH antagonist on the pregnancy rate, with current protocols, we hypothesized that a shorter duration of GnRH antagonist administration might improve outcome.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: cetrorelix acetate

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Both ovaries present with no morphological abnormalities
• Normal ovulatory cycle with cycle lengths of between 25 and 35 days
• Basal serum FSH (day 3) level of < 15 mIU/mL
• Body mass index (BMI) ranging between 18 and 27 kg/m2

Exclusion Criteria:

• History of a poor ovarian response
• Evidence of endocrine abnormalities, such as, hyperprolactinemia, thyroid dysfunction, or polycystic ovary syndrome
• Hydrosalpinx
• Severe endometriosis (stage III-IV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Stimulated as conventional protocol	Drug: cetrorelix acetate; The GnRH antagonist, cetrorelix acetate (Cetrotide; Serono) 0.25 mg was added daily, starting when the leading follicle reached 14 mm in diameter during ovarian stimulation for IVF. When the leading follicle reached a mean diameter of 18 mm or two follicles or more reached a diameter of 17 mm, 250 μg of recombinant hCG (Ovidrel; Serono) SQ was injected. In Group A, the GnRH antagonist continued to be used until the day of hCG administration. In Group B, the GnRH antagonist was not administrated on the hCG day
Experimental: B; GnRH antagonist stopped one day earlier than conventional protocol	Drug: cetrorelix acetate; The GnRH antagonist, cetrorelix acetate (Cetrotide; Serono) 0.25 mg was added daily, starting when the leading follicle reached 14 mm in diameter during ovarian stimulation for IVF. When the leading follicle reached a mean diameter of 18 mm or two follicles or more reached a diameter of 17 mm, 250 μg of recombinant hCG (Ovidrel; Serono) SQ was injected. In Group A, the GnRH antagonist continued to be used until the day of hCG administration. In Group B, the GnRH antagonist was not administrated on the hCG day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maturity of oocytes, fertilization rate, embryo quality	3 days

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Chang Suk Suh, M.D., Ph.D., Dept. of Obstetrics and Gynecology, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 11, 2007
• First Posted (Estimate): December 12, 2007

Study Record Updates

• Last Update Posted (Estimate): August 21, 2009
• Last Update Submitted That Met QC Criteria: August 20, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Cetrorelix
• Other Study ID Numbers: B-0710-050-001