Dual Trigger for Elective Fertility Preservation (DUAL-T)

July 24, 2023 updated by: Fundación Santiago Dexeus Font

Dual Trigger vs.GnRH-a Trigger for Elective Fertility Preservation. A Randomized Controlled Trial

The widespread availability of efficient contraception as well as women's increased education has led to childbearing postponement. Combined with the increased recognition of the concept of "ovarian aging", this has opened the Pandora´s box of EOC, which is currently considered a safe and cost-efficient approach among assisted reproduction techniques.

Previous studies have shown that two main factors determine the CLBR after EOC: 1) patient's age at the time of oocyte banking, and 2) the number of oocytes retrieved. Therefore, measures aiming at increasing the oocyte yield, specially the number of mature oocytes retrieved, will maximize the success of this technique.

In the last few years, the dual trigger for final oocyte maturation has emerged has an approach that seems to improve both oocyte yield and quality when compared to the hCG trigger alone. Nowadays, the standard of care in EOC patients is final oocyte maturation with a single bolus of GnRH-a. Understanding the impact of the dual trigger on the number of MII oocytes retrieved in patients undergoing EOC will improve the treatment protocols and allow for a better patient counselling.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Elective oocyte cryopreservation (EOC) has been gaining increasing importance in the last few years, driven by the widespread information regarding the concept of 'age-related fertility decline', as well as the availability of efficient contraception and women's increasing educational and professional aspirations. Considering the similar clinical outcomes regarding live birth rate after vitrified-warmed and fresh oocytes and the proven cost-effectiveness of this approach, oocyte banking is now considered an efficient technique in assisted reproduction.

Previous studies have shown that both patient's age and the number of oocytes retrieved have a significant impact on the cumulative live birth rate (CLBR) in patients undergoing EOC, highlighting the importance of maximizing oocyte yield in these patients.

In all these former reports, final follicular maturation was triggered by one bolus of human chorionic gonadotropin (hCG) or, following recent trends in clinical practice, by a single bolus of Gonadotropin Releasing Hormone agonist (GnRH-a).

More recently, the concomitant administration of both GnRH-a and a bolus of HCG prior to oocyte retrieval (dual trigger) has been proposed as a new strategy for final follicular maturation, aiming to improve oocyte and embryo quality . When compared to HCG trigger, the dual trigger adds the more physiologic follicular stimulating hormone (FSH) and luteinizing hormone (LH) peak provided by GnRH-a. With this approach, several studies have reported an increase in the number of MII oocytes retrieved, as well as in the number of good quality embryos and improved pregnancy outcomes in different subpopulations of infertile patients.

Nowadays, the standard of care in patients undergoing a freeze-all approach, either for oocyte or embryo cryopreservation, is final follicular maturation with GnRH-a due to its more physiologic and shorter surge of both LH and FSH, terminating 24h after its onset, and reducing the risk of ovarian hyperstimulation syndrome (OHSS). So far, no study has compared the dual trigger approach to the use of a single bolus of GnRH-a. By adding HCG activity and, therefore, generating higher intracellular cyclic adenosine monophosphate (cAMP) accumulation, an amplification of the steroidogenic response of the pre-ovulatory follicle might be achieved with the dual trigger when compared to the GnRH-a trigger alone.

Therefore, the investigators set out to perform this randomized controlled trial aiming to compare, for the first time, the dual trigger and the GnRH-a trigger regarding the number of MII oocytes retrieved in patients undergoing EOC.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • Spain
      • Barcelona, Spain, 08028
        • Hospital Universitario Quiron Dexeus

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

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able and willing to sign the Patient Consent Form and adhere to study visitation schedule
  • antral follicle count (AFC) <20
  • Anti-Mullerian hormone (AMH) ≤3ng/ml (AMH result of up to one year will be valid)
  • Age >=18 and ≤40 years
  • BMI >18 and <30 kg/m2

Exclusion Criteria:

  • Medically indicated fertility preservation
  • AFC ≥ 20
  • Polycystic ovarian syndrome (PCOS) according to the Rotterdam criteria
  • FSH ≥ 20
  • History of untreated autoimmune, endocrine or metabolic disorders
  • Contraindication for hormonal treatment
  • Recent history of severe disease requiring regular treatment (clinically significant concurrent medical condition that could compromise subject safety or interfered with the trial assessment).

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GnRH-a+rhCG
Ovulation triggering with GnRH-a+rhCG
Drug: Ovulation triggering with GnRH-a+rhCG
recombinant follicle stimulating hormone (rFSH) 225-300 IU (Gonal-F®/Puregon®/ Ovaleap®/Rekovelle®) Micronized progesterone 200mg (Utrogestan®) Ovulation trigger: Triptorelin 0.2 mg (Decapeptyl®) + Recombinant human chorionic gonadotropin (rhCG) 250μg (Ovitrelle®)
Active Comparator: GnRH-a
Ovulation triggering with GnRH-a
Drug: Ovulation triggering with GnRH-a
rFSH 225-300 IU (Gonal-F®/Puregon®/Ovaleap®/ Rekovelle®) Micronized progesterone 200mg (Utrogestan®) Ovulation trigger: Triptorelin 0.2 mg (Decapeptyl®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of mature oocytes (MIIs) retrieved
Time Frame: 7 -20 days from initiation of ovarian stimulation
7 -20 days from initiation of ovarian stimulation

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of oocytes retrieved
Time Frame: 7 -20 days from initiation of ovarian stimulation
7 -20 days from initiation of ovarian stimulation
Change in Progesterone values
Time Frame: Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Change in Estradiol values
Time Frame: Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Change in FSH values
Time Frame: Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Change in LH values
Time Frame: Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Ovarian hyperstimulation syndrome (OHSS) (percent)
Time Frame: Until 15 days after the end of ovarian stimulation
Until 15 days after the end of ovarian stimulation

Other Outcome Measures

Outcome Measure
Time Frame
Incidence of adverse events and serious adverse events
Time Frame: Until 15 days after the end of ovarian stimulation
Until 15 days after the end of ovarian stimulation

Collaborators and Investigators

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

Sponsor

Fundación Santiago Dexeus Font

Investigators

  • Study Chair: Nikolaos P Polyzos, MD PhD, Hospital Universitari Dexeus
  • Principal Investigator: Ana Neves, MD, Hospital Universitari Dexeus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

October 5, 2021

Primary Completion (Actual)

April 25, 2023

Study Completion (Actual)

April 25, 2023

Study Registration Dates

First Submitted

July 5, 2021

First Submitted That Met QC Criteria

July 29, 2021

First Posted (Actual)

August 5, 2021

Study Record Updates

Last Update Posted (Actual)

July 25, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FSD-PSE-2021-09
  • 2021-002467-22 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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