Ovulation Trigger Strategies in Low Ovarian Reserve (TRIGGERBEST)

NCT07816562 | Recruiting Phase 3 DMC

• 1 other identifier: TRIGGERBEST
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Low Ovarian Reserve; Poor Ovarian Response

Keywords

Low ovarian reserve; Follitropin delta; Ovulation trigger; Mature oocytes; IVF

Outcome Measures

Primary Outcomes (1)

• Number of mature oocytes (MII)

  Number of metaphase II (MII) oocytes obtained at oocyte retrieval following ovulation triggering

  During the oocyte retrieval procedure

Secondary Outcomes (3)

• Proportion of mature oocytes

  During the oocyte retrieval procedure

• Biochemical pregnancy rate per embryo transfer

  10-14 days after embryo transfer

• Ongoing pregnancy rate

  6-7 weeks of gestation

Study Arms (3)

hCG alone

EXPERIMENTAL

Ovulation triggering using human chorionic gonadotropin (hCG) alone.

Drug: Human chorionic gonadotropin (hCG)

Follitropin delta + hCG

EXPERIMENTAL

Ovulation triggering using follitropin delta in combination with human chorionic gonadotropin (hCG).

Drug: Human chorionic gonadotropin (hCG); Drug: Follitropin delta

Dual trigger

EXPERIMENTAL

Ovulation triggering using a gonadotropin-releasing hormone (GnRH) agonist in combination with human chorionic gonadotropin (hCG).

Drug: Human chorionic gonadotropin (hCG); Drug: Triptorelin

Interventions

Human chorionic gonadotropin (hCG) DRUG

Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.

Also known as: hCG

Dual trigger; Follitropin delta + hCG; hCG alone

Follitropin delta DRUG

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

Follitropin delta + hCG

Triptorelin DRUG

Triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, administered as part of the ovulation-triggering regimen for final oocyte maturation.

Dual trigger

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• More than two previous failed ovarian stimulation cycles.
• Female age \>42 years.
• Body mass index (BMI) \>35 kg/m².
• 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.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead
• Ferring Pharmaceuticals: collaborator
• Hospital Clínico Universitario de Valencia: collaborator

Study Sites (1)

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Related Publications (13)

• Kale A, Kale A. Oocyte Quality and Blastocyst Formation Rate with Dual Stimulation in Patients Belonging to POSEIDON Groups 3 and 4: A Retrospective Comparative Study. J Obstet Gynaecol India. 2023 Feb;73(1):57-61. doi: 10.1007/s13224-022-01703-1. Epub 2022 Oct 21.

  PMID: 36879944 BACKGROUND

• Zhang Q, He S, Meng Y, Yin T, Ming L, Yang J, Li S. Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels. Front Endocrinol (Lausanne). 2024 Apr 18;15:1352522. doi: 10.3389/fendo.2024.1352522. eCollection 2024.

  PMID: 38699386 BACKGROUND

• Chern CU, Li JY, Tsui KH, Wang PH, Wen ZH, Lin LT. Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: A retrospective cohort study. PLoS One. 2020 Jul 6;15(7):e0235707. doi: 10.1371/journal.pone.0235707. eCollection 2020.

  PMID: 32628729 BACKGROUND

• Alyasin A, Mehdinejadiani S, Ghasemi M. GnRH agonist trigger versus hCG trigger in GnRH antagonist in IVF/ICSI cycles: A review article. Int J Reprod Biomed. 2016 Sep;14(9):557-566.

  PMID: 27738657 BACKGROUND

• Huang Z, Wells D. The human oocyte and cumulus cells relationship: new insights from the cumulus cell transcriptome. Mol Hum Reprod. 2010 Oct;16(10):715-25. doi: 10.1093/molehr/gaq031. Epub 2010 Apr 29.

  PMID: 20435609 BACKGROUND

• Zhang Y, Yan Z, Qin Q, Nisenblat V, Chang HM, Yu Y, Wang T, Lu C, Yang M, Yang S, Yao Y, Zhu X, Xia X, Dang Y, Ren Y, Yuan P, Li R, Liu P, Guo H, Han J, He H, Zhang K, Wang Y, Wu Y, Li M, Qiao J, Yan J, Yan L. Transcriptome Landscape of Human Folliculogenesis Reveals Oocyte and Granulosa Cell Interactions. Mol Cell. 2018 Dec 20;72(6):1021-1034.e4. doi: 10.1016/j.molcel.2018.10.029. Epub 2018 Nov 21.

  PMID: 30472193 BACKGROUND

• Wissing ML, Kristensen SG, Andersen CY, Mikkelsen AL, Host T, Borup R, Grondahl ML. Identification of new ovulation-related genes in humans by comparing the transcriptome of granulosa cells before and after ovulation triggering in the same controlled ovarian stimulation cycle. Hum Reprod. 2014 May;29(5):997-1010. doi: 10.1093/humrep/deu008. Epub 2014 Feb 7.

  PMID: 24510971 BACKGROUND

• Haas J, Ophir L, Barzilay E, Yerushalmi GM, Yung Y, Kedem A, Maman E, Hourvitz A. GnRH agonist vs. hCG for triggering of ovulation--differential effects on gene expression in human granulosa cells. PLoS One. 2014 Mar 6;9(3):e90359. doi: 10.1371/journal.pone.0090359. eCollection 2014.

  PMID: 24603682 BACKGROUND

• Parks JC, Patton AL, McCallie BR, Griffin DK, Schoolcraft WB, Katz-Jaffe MG. Corona cell RNA sequencing from individual oocytes revealed transcripts and pathways linked to euploid oocyte competence and live birth. Reprod Biomed Online. 2016 May;32(5):518-26. doi: 10.1016/j.rbmo.2016.02.002. Epub 2016 Feb 24.

  PMID: 26995658 BACKGROUND

• Borgbo T, Povlsen BB, Andersen CY, Borup R, Humaidan P, Grondahl ML. Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2013 Oct;100(4):994-1001. doi: 10.1016/j.fertnstert.2013.05.038. Epub 2013 Jul 12.

  PMID: 23856575 BACKGROUND

• Yu EJ, Choi WY, Park MS, Eum JH, Lee DR, Lee WS, Lyu SW, Yoon SY. RNA sequencing-based transcriptome analysis of granulosa cells from follicular fluid: Genes involved in embryo quality during in vitro fertilization and embryo transfer. PLoS One. 2023 Mar 1;18(3):e0280495. doi: 10.1371/journal.pone.0280495. eCollection 2023.

  PMID: 36857405 BACKGROUND

• Uyar A, Torrealday S, Seli E. Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril. 2013 Mar 15;99(4):979-97. doi: 10.1016/j.fertnstert.2013.01.129.

  PMID: 23498999 BACKGROUND

• Haahr T, Dosouto C, Alviggi C, Esteves SC, Humaidan P. Management Strategies for POSEIDON Groups 3 and 4. Front Endocrinol (Lausanne). 2019 Sep 11;10:614. doi: 10.3389/fendo.2019.00614. eCollection 2019.

  PMID: 31572298 BACKGROUND

MeSH Terms

Interventions

Chorionic Gonadotropin; follitropin delta; Triptorelin Pamoate

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins

Study Officials

• Cesar Lizan Tudela

  Department of Obstetrics and Gynaecology, Hospital Clínico Universitario de Valencia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cesar Lizan Tudela

CONTACT

+34 96 197 3500; cesarlizan@yahoo.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of three parallel groups, each receiving a different ovulation trigger strategy.

Study Record Dates

• First Submitted: March 21, 2026
• First Posted: September 11, 2026
• Study Start: September 17, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 11, 2026

Record last verified: 2026-09

Locations

ES (1)