Dual Trigger for Elective Fertility Preservation

NCT04992468 | Completed Phase 4

• 2 other identifiers: FSD-PSE-2021-092021-002467-22
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

• Number of mature oocytes (MIIs) retrieved

  7 -20 days from initiation of ovarian stimulation

Secondary Outcomes (6)

• Number of oocytes retrieved

  7 -20 days from initiation of ovarian stimulation

• Change in Progesterone values

  Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl

• Change in Estradiol values

  Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl

• Change in FSH values

  Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl

• Change in LH values

  Day 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl

Other Outcomes (1)

• Incidence of adverse events and serious adverse events

  Until 15 days after the end of ovarian stimulation

Study Arms (2)

GnRH-a+rhCG

EXPERIMENTAL

Ovulation triggering with GnRH-a+rhCG

Drug: Ovulation triggering with GnRH-a+rhCG

GnRH-a

ACTIVE COMPARATOR

Ovulation triggering with GnRH-a

Drug: Ovulation triggering with GnRH-a

Interventions

Ovulation triggering with GnRH-a+rhCG DRUG

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®)

GnRH-a+rhCG

Ovulation triggering with GnRH-a DRUG

rFSH 225-300 IU (Gonal-F®/Puregon®/Ovaleap®/ Rekovelle®) Micronized progesterone 200mg (Utrogestan®) Ovulation trigger: Triptorelin 0.2 mg (Decapeptyl®)

GnRH-a

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fundación Santiago Dexeus Font: lead

Study Sites (1)

Hospital Universitario Quiron Dexeus

Barcelona, 08028, Spain

Location

Related Publications (18)

• Ovarian Stimulation TEGGO, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, La Marca A, Lainas G, Le Clef N, Massin N, Mastenbroek S, Polyzos N, Sunkara SK, Timeva T, Toyli M, Urbancsek J, Vermeulen N, Broekmans F. ESHRE guideline: ovarian stimulation for IVF/ICSIdagger. Hum Reprod Open. 2020 May 1;2020(2):hoaa009. doi: 10.1093/hropen/hoaa009. eCollection 2020.

  PMID: 32395637 BACKGROUND

• Casarini L, Lispi M, Longobardi S, Milosa F, La Marca A, Tagliasacchi D, Pignatti E, Simoni M. LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling. PLoS One. 2012;7(10):e46682. doi: 10.1371/journal.pone.0046682. Epub 2012 Oct 5.

  PMID: 23071612 BACKGROUND

• Cobo A, Garcia-Velasco J, Domingo J, Pellicer A, Remohi J. Elective and Onco-fertility preservation: factors related to IVF outcomes. Hum Reprod. 2018 Dec 1;33(12):2222-2231. doi: 10.1093/humrep/dey321.

  PMID: 30383235 BACKGROUND

• Cobo A, Garcia-Velasco JA, Coello A, Domingo J, Pellicer A, Remohi J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril. 2016 Mar;105(3):755-764.e8. doi: 10.1016/j.fertnstert.2015.11.027. Epub 2015 Dec 10.

  PMID: 26688429 BACKGROUND

• Devine K, Mumford SL, Goldman KN, Hodes-Wertz B, Druckenmiller S, Propst AM, Noyes N. Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth. Fertil Steril. 2015 Jun;103(6):1446-53.e1-2. doi: 10.1016/j.fertnstert.2015.02.029. Epub 2015 Mar 23.

  PMID: 25813281 BACKGROUND

• Ding N, Liu X, Jian Q, Liang Z, Wang F. Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:92-98. doi: 10.1016/j.ejogrb.2017.09.004. Epub 2017 Sep 14.

  PMID: 28957685 BACKGROUND

• Doyle JO, Richter KS, Lim J, Stillman RJ, Graham JR, Tucker MJ. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval. Fertil Steril. 2016 Feb;105(2):459-66.e2. doi: 10.1016/j.fertnstert.2015.10.026. Epub 2015 Nov 18.

  PMID: 26604065 BACKGROUND

• Fauser BC, de Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J, van Hooren HG. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002 Feb;87(2):709-15. doi: 10.1210/jcem.87.2.8197.

  PMID: 11836309 BACKGROUND

• Golan A, Weissman A. Symposium: Update on prediction and management of OHSS. A modern classification of OHSS. Reprod Biomed Online. 2009 Jul;19(1):28-32. doi: 10.1016/s1472-6483(10)60042-9.

  PMID: 19573287 BACKGROUND

• Goldman RH, Racowsky C, Farland LV, Munne S, Ribustello L, Fox JH. Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients. Hum Reprod. 2017 Apr 1;32(4):853-859. doi: 10.1093/humrep/dex008.

  PMID: 28166330 BACKGROUND

• Griffin D, Feinn R, Engmann L, Nulsen J, Budinetz T, Benadiva C. Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril. 2014 Aug;102(2):405-9. doi: 10.1016/j.fertnstert.2014.04.028. Epub 2014 May 17.

  PMID: 24842671 BACKGROUND

• Haas J, Bassil R, Samara N, Zilberberg E, Mehta C, Orvieto R, Casper RF. GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study. Hum Reprod. 2020 Jul 1;35(7):1648-1654. doi: 10.1093/humrep/deaa107.

  PMID: 32563188 BACKGROUND

• Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril. 2013 Nov;100(5):1296-302. doi: 10.1016/j.fertnstert.2013.07.1976. Epub 2013 Aug 28.

  PMID: 23993928 BACKGROUND

• van Loendersloot LL, Moolenaar LM, Mol BW, Repping S, van der Veen F, Goddijn M. Expanding reproductive lifespan: a cost-effectiveness study on oocyte freezing. Hum Reprod. 2011 Nov;26(11):3054-60. doi: 10.1093/humrep/der284. Epub 2011 Sep 6.

  PMID: 21896545 BACKGROUND

• Mills M, Rindfuss RR, McDonald P, te Velde E; ESHRE Reproduction and Society Task Force. Why do people postpone parenthood? Reasons and social policy incentives. Hum Reprod Update. 2011 Nov-Dec;17(6):848-60. doi: 10.1093/humupd/dmr026. Epub 2011 Jun 7.

  PMID: 21652599 BACKGROUND

• Montoya-Botero P, Martinez F, Rodriguez-Purata J, Rodriguez I, Coroleu B, Polyzos NP. The effect of type of oral contraceptive pill and duration of use on fresh and cumulative live birth rates in IVF/ICSI cycles. Hum Reprod. 2020 Apr 28;35(4):826-836. doi: 10.1093/humrep/dez299.

  PMID: 32163564 BACKGROUND

• Orvieto R. Triggering final follicular maturation: hCG, GnRH-agonist, or both, when and to whom? J Assist Reprod Genet. 2017 Sep;34(9):1231-1232. doi: 10.1007/s10815-017-0982-7. Epub 2017 Jun 27. No abstract available.

  PMID: 28656537 BACKGROUND

• Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014 Oct 31;2014(10):CD008046. doi: 10.1002/14651858.CD008046.pub4.

  PMID: 25358904 BACKGROUND

Related Links

• Department of Obstetrics, Gynaecology and Reproduction Hospital Universitari Quiron Dexeus

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Nikolaos P Polyzos, MD PhD

  Hospital Universitari Dexeus

  STUDY CHAIR

• Ana Neves, MD

  Hospital Universitari Dexeus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: August 5, 2021
• Study Start: October 5, 2021
• Primary Completion: April 25, 2023
• Study Completion: April 25, 2023
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)