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

Sponsor

American University of Beirut Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03169166

Collaborator

(none)

282

Enrollment

Location

Arms

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sterility Infertility	Drug: Triptorelin	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

282 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2017

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Ongoing pregnancy rate in hyper-responder women undergoing assisted reproductive technology cycles [20 weeks from Last Menstrual Period (LMP)]

Secondary Outcome Measures

Oocyte collection rate [On the day of ovum pick-up]
oocyte maturation rate ovarian volume on the day of hCG titer

Other Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.