The Effect of Dual Trigger (GnRH Agonist + hCG) for Final Maturation in Oocyte Donors With History of a Previous Cycle With Suboptimal Response to GnRH Agonist Only Trigger

The goal of this clinical trial is to compare GnRH-agonist trigger with dual GnRH-agonist and HCG trigger in oocyte donors.

The main questions it aims to answer are:

• Maturation rate (Metaphase II/ Total number of COCs collected)
• Fertilization rate
• Embryo quality day 3
• Fragmentation rate embryo day 3
• Blastulation rate (Day5/6/7)
• Quality of blastocyst (Gardner criteria) Participants will undergo controlled ovarian stimulation with a GnRH antagonist protocol Researchers will compare the effects of final maturation with GnRH-agonist trigger to a dual trigger (hCG and GnRH-a)

Study Overview

• Status: Recruiting
• Conditions: Ovarian Stimulation; Oocyte Donors; Human Chorionic Gonadotropin
• Intervention / Treatment: Drug: Dual trigger (human chorionic gonadotropin plus GnRH-agonist); Drug: GnRH-agonist only trigger

Detailed Description

Final oocyte maturation is a critical step in the process of the Assisted Reproductive Technology (ART) treatment and has a certain impact on oocyte yield and oocyte competency. There are three different types of trigger: hCG, GnRH-agonist or dual trigger (hCG and GnRH-agonist combined), and the choice depends on the ovarian stimulation protocol, the ovarian response and on the clinical standard of the IVF clinic. As oocyte donors are at high risk for OHSS, a GnRH-agonist trigger (GnRH-a) is the most commonly used modality for triggering final maturation. However, a certain number of oocyte donors may have a suboptimal response to GnRH-a trigger only, with a yield of oocytes less than the 10th percentile, with a clear negative impact on oocyte efficiency and competency. This study aims to evaluate whether oocyte competence can be improved in oocyte donors with a previously suboptimal response to GnRH-a, by using a dual trigger in a subsequent ovarian stimulation cycle, in which hCG is added to the GnRH-agonist for final maturation

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

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 55133
    • Recruiting
    • Embryolab Fertility Clinic
    • Contact: Nikolaos Christoforidis, MD; Phone Number: +302310474747; Email: n.christoforidis@embryolab.eu
    • Contact: Dimitrios Michalakis, MD; Email: d.michalakis@embryolab.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI: 18 - 25
• AMH: 1-3ng/ml
• AFC: 15
• Peak E2 in previous ovarian stimulation cycle: < 4000 pg/ml
• Ovarian response in first stimulation cycle: < 20 follicles over 10mm in total, at time of triggering
• Peak E2 in study cycle: < 4000 pg/ml
• Suboptimal response to trigger medication at first stimulation cycle
• Male age < 50 years old with normospermia

Exclusion Criteria:

• Oocyte donors which are at risk for development of ovarian hyperstimulation syndrome (OHSS)

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: Dual trigger (GnRH-agonist plus hCG); Participants in this arm will be administered a GnRH-agonist trigger plus hCG (dual trigger) for final maturation	Drug: Dual trigger (human chorionic gonadotropin plus GnRH-agonist); Human chorionic gonadotropin will be added to GnRH-agonist as a dual trigger in participants previously having had a suboptimal response to GnRH-agonist trigger only
Active Comparator: Gn-RH-agonist only trigger; Participants in this arm will be administered a GnRH-agonist trigger only for final maturation	Drug: GnRH-agonist only trigger; GnRH-agonist only will be used for final maturation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oocyte maturation rate	Number of metaphase II oocytes per total number of oocytes retrieved in oocyte pick-up day	18 months prospective trial
Fertilization rate	number of 2PN embryos per total number of MII oocytes fertilised	18 months prospective trial
Blastulation rate	Number of blastocysts up to day 6 per number of fertilised 2PN embryos	18 months prospective trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of recipients per donor cycle	The number of recipients matched per donor	18 months prospective trial
Ongoing Pregnancy Rate	number of pregnancies with positive fetal heart per number of embryotransfers performed	28 months prospective trial
Live Birth Rate	number of live births per number of embryotransfers performed	28 months prospective trial

Collaborators and Investigators

• Sponsor: Embryolab Fertility Clinic
• Collaborators: ART Fertility Clinics LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: November 20, 2023
• First Posted (Estimated): November 21, 2023

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Dual trigger; GnRH agonist; Oocyte Donors
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Chorionic Gonadotropin; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 012023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the trial completion IPD are to be shared with researchers from ART Fertility Clinics for statistical analysis
• IPD Sharing Time Frame: at the end of study as already submitted
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No