The Use of GnRH Agonist Trigger for Final Follicle Maturation in Women Undergoing Assisted Reproductive Technologies

The Use of GnRH Agonist Trigger for Final Follicle Maturation in Women Undergoing Assisted Reproductive Technologies: A Prospective Randomized Controlled Trial

This is a prospective comparative randomized controlled trial investigating the effect of two GnRH agonist trigger protocols on the ongoing pregnancy rate in hyper-responder women undergoing assisted reproductive technology.

Study Overview

• Status: Completed
• Conditions: Infertility; Sterility
• Intervention / Treatment: Drug: Triptorelin

Detailed Description

Follicle maturation triggering is the final differentiation process of an immature egg before fertilization, either in normal or stimulated ovarian cycles in assisted reproductive techniques. This step has traditionally been accomplished by the administration of human chorionic gonadotropin (hCG) trigger which mimics LH activity. However, hCG is a primary cause of severe ovarian hyperstimulation syndrome (OHSS) in women and appears to initiate the complex cascade that leads to the development of serious medical complications. Numerous strategies have been suggested to prevent OHSS; one of these is the administration of a gonadotropin releasing hormone (GnRH) agonist trigger instead of hCG. Despite a high safety profile, the GnRH agonist trigger of follicle maturation was found to be associated with a decreased probability of clinical and ongoing pregnancy rates and very high miscarriage rates. A profoundly deficient luteal phase is believed to be the cause of compromised reproductive outcome. Our personal clinical practice at the AUBMC Fertility Center seems to indicate that a novel GnRH agonist administration protocol is associated with a comparable reproductive performance to standard hCG trigger. In this study, we aim to validate the above clinical impression and assess associated parameters of success. Therefore, a prospective comparative randomized controlled trial will be performed in order to investigate the effect of three repeated doses of GnRH agonist trigger "Triptorelin" accompanied by intensive Luteal Support on the ongoing pregnancy outcome in women who are hyper-responders to ovarian stimulation when undergoing assisted reproductive technology.

• Study Type: Interventional
• Enrollment (Actual): 277
• Phase: Phase 4

Contacts and Locations

Study Locations

• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Normal uterine cavity (as assessed by hysteroscopy or HSG).
• Normal hormonal investigation: TSH, PRL.
• More than 15 follicles (≥12 mm in diameter) on ultrasound, and/or estradiol level of > 3500 pg/ml on the day of trigger.

Exclusion Criteria:

• History of three or more miscarriages.
• History of three or more previous IVF failures.
• Abnormal uterine cavity (Hysteroscopy or HSG).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Repeated 3-dose GnRHa " Triptorelin"; Triptorelin pre-filled syringes (Gonapeptyl 0.1mg; Ferring GmbH, Germany) will be administered subcutaneously in three repeated doses 12 hours apart (0.3/0.2/0.2mg) when at least three follicles 18 mm in diameter have been observed by ultrasound examination.	Drug: Triptorelin; Triptorelin pre-filled syringes (Gonapeptyl 0.1mg; Ferring GmbH, Germany) will be administered subcutaneously in three repeated doses 12 hours apart; Other Names: Gonapeptyl
No Intervention: Conventional 1-dose GnRHa " Triptorelin"; Triptorelin pre-filled syringes will be administered subcutaneously in a single dose (0.3 mg) when at least three follicles 18 mm in diameter have been observed by ultrasound examination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ongoing pregnancy rate in hyper-responder women undergoing assisted reproductive technology cycles	20 weeks from Last Menstrual Period (LMP)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oocyte collection rate	oocyte maturation rate ovarian volume on the day of hCG titer	On the day of ovum pick-up

Other Outcome Measures

Outcome Measure	Time Frame
Fertilization rate	16-18 hours post insemination
Total pregnancy rate	10-12 days from embryo transfer
Clinical pregnancy rate	7 weeks from LMP
Implantation rate	7 weeks from LMP
Miscarriage rate	From a positive pregnancy test till 20 weeks gestation

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Investigators: Principal Investigator: Johnny Awwad, MD, American University of Beirut Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: May 25, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; Assisted Reproductive Technology; GnRH agonist; In Vitro fertilization; Follicule Maturation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: AmericanUBMCGNRH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No