Ovulation Trigger Strategies in Low Ovarian Reserve (TRIGGERBEST) (TRIGGERBEST)
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.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Cesar Lizan Tudela
- Telefonní číslo: +34 96 197 3500
- E-mail: cesarlizan@yahoo.es
Studijní místa
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Valencia, Španělsko, 46010
- Nábor
- Hospital Clínico Universitario de Valencia
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Kontakt:
- Cesar Lizan Tudela
- Telefonní číslo: +34 96 197 3500
- E-mail: cesarlizan@yahoo.es
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: hCG alone
Ovulation triggering using human chorionic gonadotropin (hCG) alone.
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Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Ostatní jména:
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Experimentální: Follitropin delta + hCG
Ovulation triggering using follitropin delta in combination with human chorionic gonadotropin (hCG).
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Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Ostatní jména:
Follitropin delta administered as part of the ovulation-triggering regimen for final oocyte maturation. (hCG). |
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Experimentální: Dual trigger
Ovulation triggering using a gonadotropin-releasing hormone (GnRH) agonist in combination with human chorionic gonadotropin (hCG).
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Human chorionic gonadotropin (hCG) administered for final oocyte maturation and ovulation triggering.
Ostatní jména:
Triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, administered as part of the ovulation-triggering regimen for final oocyte maturation.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Number of mature oocytes (MII)
Časové okno: During the oocyte retrieval procedure
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Number of metaphase II (MII) oocytes obtained at oocyte retrieval following ovulation triggering
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During the oocyte retrieval procedure
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Proportion of mature oocytes
Časové okno: During the oocyte retrieval procedure
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Percentage of metaphase II (MII) oocytes relative to the total number of oocytes retrieved.
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During the oocyte retrieval procedure
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Biochemical pregnancy rate per embryo transfer
Časové okno: 10-14 days after embryo transfer
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Positive beta-human chorionic gonadotropin (beta-hCG) test following fresh embryo transfer.
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10-14 days after embryo transfer
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Ongoing pregnancy rate
Časové okno: 6-7 weeks of gestation
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Presence of a viable intrauterine pregnancy confirmed by ultrasound.
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6-7 weeks of gestation
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Cesar Lizan Tudela, Department of Obstetrics and Gynaecology, Hospital Clínico Universitario de Valencia
Publikace a užitečné odkazy
Obecné publikace
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Hormony
- Hormony, hormonální náhražky a antagonisté hormonů
- Hormony uvolňující hypofýzy
- Hypothalamické hormony
- Peptidové hormony
- Neuropeptidy
- Peptidy
- Aminokyseliny, peptidy a proteiny
- Oligopeptidy
- Proteiny nervové tkáně
- Proteiny
- Hormon uvolňující gonadotropin
- Gonadotropiny
- Placentární hormony
- Těhotenské proteiny
- Triptorelin Pamoát
- Choriový gonadotropin
- Follitropin Delta
Další identifikační čísla studie
- TRIGGERBEST
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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