Ovulation Trigger Strategies in Low Ovarian Reserve (TRIGGERBEST) (TRIGGERBEST)

September 9, 2026 updated by: Fundación para la Investigación del Hospital Clínico de Valencia

Ovulation Trigger Strategies in Women With Low Ovarian Reserve Undergoing Fresh In Vitro Fertilization Cycles: A Prospective Randomized Controlled Trial (TRIGGERBEST)

This study aims to compare different ovulation triggering strategies in women with low ovarian reserve undergoing fresh in vitro fertilization (IVF) cycles.

Ovulation triggering is a key step in IVF treatment, as it determines final oocyte maturation prior to oocyte retrieval.

Participants are randomly assigned to one of three ovulation trigger approaches: human chorionic gonadotropin (hCG) alone, follitropin delta combined with hCG, or dual trigger using a gonadotropin-releasing hormone (GnRH) agonist plus hCG.

The primary objective is to evaluate wether adding follitropin delta at the time of triggering increases the number of matura oocytes obtained, without adversely affecting implantation rates. Pregnancy otucomes following fresh embryo transfer will also be assessed.

The results of this study may help optimize ovulation triggering strategies in women with low ovarian reserve undergoing IVF treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Final oocyte maturation is a critical step in assisted reproductive techniques (ART) and is largely determined by the ovulation triggering strategy. In women with low ovarian reserve, achieving an adequate number of mature oocytes remains a major challenge, even when established trigger protocols are used.

Dual trigger strategies combining hCG and a GnRH agonist are widely used in this population, based on evidence suggesting improved oocyte maturation. However, despite this approach, oocyte yield and maturity often remain suboptimal. The addition of exogenous follicle-stimulating hormone (FSH) activity at the time of ovulation triggering has been proposed as a potential strategy to further optimize final oocyte maturation.

Follitropin delta has a distinct pharmacokinetic profile and provides individualized FSH exposure based on ovarian reserve markers. Its use in combination with hCG at the time of triggering may enhance oocyte maturation without compromising endometrial receptivity.

This prospective, randomized study compares three ovulation triggering strategies in women with low ovarian reserve undergoing fresh IVF cycles: hCG alone, follitropin delta combined with hCG, and dual triggering using a GnRH agonist plus hCG. Participants are randomly assigned to one of the three groups.

The primary outcome is the number of mature oocytes (metaphase II, MII) obtained at oocyte retrieval. Secondary outcomes include the proportion of mature oocytes, biochemical pregnancy rate per embryo transfer, and ongoing pregnancy rate following fresh embryo transfer.

The study aims to generate evidence to optimize ovulation triggering strategies in women with low ovarian reserve.

Study Type

Interventional

Enrollment (Estimated)

126

Phase

  • Phase 3

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 Locations

  • Spain
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clinico Universitario de Valencia
        • Contact:

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

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed informed consent.
  • Women aged between 18 and 42 years.
  • Primary infertility.
  • Women with low ovarian response classified within one of the groups defined by the POSEIDON criteria.

Exclusion Criteria:

  • More than two previous failed ovarian stimulation cycles.
  • Female age >42 years.
  • Body mass index (BMI) >35 kg/m².
  • Criteria of extremely low ovarian reserve according to the Spanish National Health System exclusion criteria (AMH <0.3 ng/mL and/or antral follicle count <5).
  • Male partner age >55 years.
  • Severe male factor infertility (total motile sperm count <1 million).
  • Previous voluntary sterilization (vasectomy or bilateral tubal ligation).
  • Previous healthy child shared by the couple.
  • Presence of medical conditions contraindicating pregnancy.
  • Risk of ovarian hyperstimulation syndrome (OHSS). If more than 15 follicles are expected on the day of trigger, the patient will be excluded from the study.

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
Intervention / Treatment
Experimental: hCG alone
Ovulation triggering using human chorionic gonadotropin (hCG) alone.
Drug: Human chorionic gonadotropin (hCG)
Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Other Names:
  • hCG
Experimental: Follitropin delta + hCG
Ovulation triggering using follitropin delta in combination with human chorionic gonadotropin (hCG).
Drug: Human chorionic gonadotropin (hCG)
Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Other Names:
  • hCG
Drug: Follitropin delta

Follitropin delta administered as part of the ovulation-triggering regimen for final oocyte maturation.

(hCG).
Experimental: Dual trigger
Ovulation triggering using a gonadotropin-releasing hormone (GnRH) agonist in combination with human chorionic gonadotropin (hCG).
Drug: Human chorionic gonadotropin (hCG)
Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Other Names:
  • hCG
Drug: Triptorelin
Triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, administered as part of the ovulation-triggering regimen for final oocyte maturation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of mature oocytes (MII)
Time Frame: During the oocyte retrieval procedure
Number of metaphase II (MII) oocytes obtained at oocyte retrieval following ovulation triggering
During the oocyte retrieval procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of mature oocytes
Time Frame: During the oocyte retrieval procedure
Percentage of metaphase II (MII) oocytes relative to the total number of oocytes retrieved.
During the oocyte retrieval procedure
Biochemical pregnancy rate per embryo transfer
Time Frame: 10-14 days after embryo transfer
Positive beta-human chorionic gonadotropin (beta-hCG) test following fresh embryo transfer.
10-14 days after embryo transfer
Ongoing pregnancy rate
Time Frame: 6-7 weeks of gestation
Presence of a viable intrauterine pregnancy confirmed by ultrasound.
6-7 weeks of gestation

Collaborators and Investigators

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

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

Collaborators

Ferring Pharmaceuticals
Hospital Clínico Universitario de Valencia

Investigators

  • Principal Investigator: Cesar Lizan Tudela, Department of Obstetrics and Gynaecology, Hospital Clínico Universitario de Valencia

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

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)

September 17, 2024

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

March 21, 2026

First Submitted That Met QC Criteria

September 9, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 9, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRIGGERBEST

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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