The Effect of Dual Trigger for Final Oocyte Maturation on IVF/ICSI Outcomes in Patients With Suboptimal Ovarian Response

June 14, 2023 updated by: Royan Institute

Royan Institute for Reproductive Biomedicine

Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a sub-optimal ovarian response.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Ovulation stimulation will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. Recently, in patients with a suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et al. (2014) reported that in patients who had more than 25% immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since studies in this field are limited, the researchers decided to design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final oocyte maturation in patients with a suboptimal ovarian response.

Controlled Ovulation stimulation (COS) will be performed in all patients with the Standard GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte maturation, at this time, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4. The required number of blocks will be randomly selected according to sample size.

The final ovarian stimulation (oocyte triggering) will be performed in groups A and B as follows:

Group A (Experimental): 0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously.

Group B (Control): Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously.

The COS cycles with less than two follicles will be cancelled s. Ovum pick up is performed 32-34 hours after oocyte triggering, and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.

The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG trigger and the number of mature (MII) oocytes collected after conventional versus delayed-start ovarian stimulation protocol. Secondary outcome measures are including total number of oocytes retrieved, oocyte maturity rate (number of MII oocytes/total number of oocytes), oocyte yield (total number of oocytes retrieved/ antral follicle count [AFC]), mature oocyte yield (number of mature oocytes retrieved/AFC), total dosage of gonadotropin (recombinant FSH and/or highly purified hMG) needed, number of days needed for ovarian stimulation, quality of obtained embryos, fertilization rate (the proportion of total number of two-pronuclear [2PN] stage zygotes /per total injected MII oocytes), implantation rate (total number of observed gestational sac/ number of transferred embryos) and clinical pregnancy rate (presence of fetal heart beat by transvaginal ultrasound per embryo transfer).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Patients with poor ovarian response (POR) diagnosis according to the POSEIDON stratification system (as POSEIDON group 1) with following criteria :

  • Women' age under 35 years;
  • Previous unexpected poor or suboptimal ovarian response after using conventional protocols (subgroup 1a: < 4 oocytes ) and (subgroup 1b: 4-9 oocytes retrieved)
  • Adequate ovarian reserve (antral follicle count ≥5 on menstrual cycle day 2-3; and basal serum AMH ≥ 1.2 ng/ml)

Exclusion Criteria:

  • Ovarian failure including basal FSH above 20 IU/l or no antral follicle by ultrasound examination;
  • Endometriosis grade 3 or higher;
  • Severe male infertility (surgical sperm extraction: TESE, PESA)
  • Body mass index >30 kg/ m2
  • History of uterine surgery as well as sub-mucosal and intramural fibroids greater than 5 cm or uterine polyps
  • Treatment cycles with pre-implantation genetic diagnosis, blastocyst and donation embryo transfer indications
  • Cigarette and drug addiction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group A (Experimental oocyte triggering approach)
0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered subcutaneously simultaneously for final oocyte triggering.
Other: Dual triggering
Adding GnRH agonist (0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) to routine oocyte triggering (two ampoules of Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) is defined as dual triggering.
No Intervention: Group B (Routine oocyte triggering approach)
Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be injected subcutaneously for final oocyte triggering.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Total number of retrieved oocytes
Time Frame: Day of oocyte pick-up (32-34 hours after hCG administration)
In one hour after ovum pick-up, outcome measurement will be possible.
Day of oocyte pick-up (32-34 hours after hCG administration)
Total number of mature or metaphase II (MII) oocytes
Time Frame: Day of oocyte pick-up ( 32-34 hours after hCG administration )
In one hour after ovum pick-up, counting the total number of MII oocytes will be possible.
Day of oocyte pick-up ( 32-34 hours after hCG administration )
Oocyte recovery ratio
Time Frame: 32-34 hours after oocyte triggering
Ratio of the total number of follicles above 18 mm to the total number of retrieved oocytes
32-34 hours after oocyte triggering

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fertilization rate
Time Frame: Day 1 post oocyte retrieval
The number of 2 pronucleus (2pn) oocytes per number of injected and/or inseminated MII oocytes
Day 1 post oocyte retrieval
Quality of obtained embryos: grade
Time Frame: 3 days after in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) procedure
The quality of embryos was graded from 1 to 3 under inverted microscope 3 days after IVF/ICSI procedure. Embryos with even-sized blastomers and/or ≤10% fragments were classified as Grade 1 (Excellent or good quality). Grade 2 embryos (moderate or fair quality) had blastomeres with slightly-moderate size differences and/or 10- 20% fragments. Grade 3 embryos (poor quality) had markedly different-sized blastomers and/or >20% fragments.
3 days after in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Royan Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Maryam Hafezi, M.D., Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Research ID (96000024)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The principle investigator of study can share IPD after finishing the study and publishing the results.

IPD Sharing Time Frame

After finishing the study and publishing the results.

IPD Sharing Access Criteria

Contact the principal investigator by Email.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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