Does Recombinant FSH (rFSH, i.g. Gonal F®) as Compared to Human Menopausal Gonadotrophin (hMG) Affect Telomere Length of Cumulus Cells During Antral Follicle Growth and Impact Blastocyst Status?

NCT06732843 | Recruiting

• 1 other identifier: 2212-ABU-012-DN
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Gonal-F® (follitropin alfa) is a recombinant FSH without LH activity, while Menopur® contains both LH and hCG. The MEGASET trial compared Menopur® and Gonal-F® in GnRH antagonist cycles with SET, showing similar efficacy. A subsequent study (MEGASET-HR) in high responders found ongoing pregnancy rates of 35.5% for Menopur® and 30.7% for Gonal-F®, with a lower early pregnancy loss for Menopur® (14.5% vs 25.5%). Telomere length (TL) in oocyte cumulus cells (CC) correlates with oocyte quality and embryo outcomes. This study aims to assess whether stimulation type (hMG vs. Gonal-F) affects TL in CC and subsequent blastocyst development. A randomized, open-label, cross-over study in normo-responders will analyze telomere length, embryo quality, and hormonal markers.

Conditions

OVARIAN STIMULATION; Telomere Length; Telomere Length, Mean Leukocyte

Keywords

recombinant human follicle-stimulating hormone (rFSH); uman-menopausal-gonadotropin (hMG; ocyte quality; embryo quality; blastocyst development; Menopur; GonalF; GnRH antagonist cycles; trophectoderm; cumulus cells

Outcome Measures

Primary Outcomes (1)

• In this study the investigators will investigate the telomere length of cumulus cells between two stimulation cycles, using different stimulation medication (rFSH versus hMG) within same patient/woman

  In this study the investigators will investigate the telomere length of cumulus cells between two stimulation cycles, using different stimulation medication (rFSH versus hMG) within same patient/woman

  12 weeks

Study Arms (1)

Normo-ovarian response patients who undergo an IVF treatment including PGT-A

Patients will follow the stimulation protocol outlined below: Initial doses will be based on ovarian reserve parameters, with the starting dosage identical for both stimulation cycles (Gonal-F® or hMG): Dose adjustments may be made starting from day 6 Antagonist suppression will be fixed from day 5 onwards Final oocyte maturation will be triggered with a dual trigger: 2,500 IU urinary hCG and 0.3 mg Decapeptyl.

Eligibility Criteria

• Age: 18 Years - 38 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Normo-ovarian response patients who undergo an IVF treatment.

You may qualify if:

• Maternal age 18 - 38 years
• Patients requested PGT-A
• BMI 18- 30kg/m2
• Expected normoresponders
• Fresh autologous ejaculate (≥5 mill/ml)
• Sperm abstinence: 2-3 days
• Normal female/male karyotype
• Regular menstrual cycle length: 25-32 days
• AFC of 5-10 in each ovary at the beginning of the stimulation
• Trigger: dual trigger: 2.500 IU urinary hCG + 0.3 mg Decapeptyl. (13)
• A wash-out period between 1 to 3 months; an inter-cycle variation of 10% in AFC, measured by the same physician, is accepted.
• Couple agrees to perform two stimulations before continuing with embryo transfer

You may not qualify if:

• \. Uterine abnormalities as diagnosed by ultrasound 2. Any hormonal or oral contraceptive pretreatment of 3 months preceding the treatment 3. Endometriosis according to American Fertility Society (AFS) ≥3 4. ≥ 2 miscarriages 5. Bologna criteria poor responders (14)

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

ART Fertility Clinics

Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

RECRUITING

Related Publications (16)

• Yu TN, Cheng EH, Tsai HN, Lin PY, Chen CH, Huang CC, Lee TH, Lee MS. Assessment of Telomere Length and Mitochondrial DNA Copy Number in Granulosa Cells as Predictors of Aneuploidy Rate in Young Patients. J Clin Med. 2022 Mar 25;11(7):1824. doi: 10.3390/jcm11071824.

  PMID: 35407431 BACKGROUND

• Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999 Jun;11(3):307-11. doi: 10.1097/00001703-199906000-00013.

  PMID: 10369209 BACKGROUND

• Younis JS, Ben-Ami M, Ben-Shlomo I. The Bologna criteria for poor ovarian response: a contemporary critical appraisal. J Ovarian Res. 2015 Nov 17;8:76. doi: 10.1186/s13048-015-0204-9.

  PMID: 26577149 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

• Butts S, Riethman H, Ratcliffe S, Shaunik A, Coutifaris C, Barnhart K. Correlation of telomere length and telomerase activity with occult ovarian insufficiency. J Clin Endocrinol Metab. 2009 Dec;94(12):4835-43. doi: 10.1210/jc.2008-2269. Epub 2009 Oct 28.

  PMID: 19864453 BACKGROUND

• Liu JP, Li H. Telomerase in the ovary. Reproduction. 2010 Aug;140(2):215-22. doi: 10.1530/REP-10-0008. Epub 2010 Jun 18.

  PMID: 20562297 BACKGROUND

• Fu D, Collins K. Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation. Mol Cell. 2007 Dec 14;28(5):773-85. doi: 10.1016/j.molcel.2007.09.023.

  PMID: 18082603 BACKGROUND

• Riethman H, Ambrosini A, Paul S. Human subtelomere structure and variation. Chromosome Res. 2005;13(5):505-15. doi: 10.1007/s10577-005-0998-1.

  PMID: 16132815 BACKGROUND

• Vasilopoulos E, Fragkiadaki P, Kalliora C, Fragou D, Docea AO, Vakonaki E, Tsoukalas D, Calina D, Buga AM, Georgiadis G, Mamoulakis C, Makrigiannakis A, Spandidos DA, Tsatsakis A. The association of female and male infertility with telomere length (Review). Int J Mol Med. 2019 Aug;44(2):375-389. doi: 10.3892/ijmm.2019.4225. Epub 2019 May 31.

  PMID: 31173155 BACKGROUND

• Cheng EH, Chen SU, Lee TH, Pai YP, Huang LS, Huang CC, Lee MS. Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Hum Reprod. 2013 Apr;28(4):929-36. doi: 10.1093/humrep/det004. Epub 2013 Feb 1.

  PMID: 23377770 BACKGROUND

• Kosebent EG, Uysal F, Ozturk S. Telomere length and telomerase activity during folliculogenesis in mammals. J Reprod Dev. 2018 Dec 14;64(6):477-484. doi: 10.1262/jrd.2018-076. Epub 2018 Sep 28.

  PMID: 30270279 BACKGROUND

• 5. J. Michaeli, K. Rotshenker Olshinka, N. Srebnik, R. Smoom, N. Serruya, S. Yanai, O. Michaeli, T. Eldar-Geva, Y. Tzfati. Oral communication in ESHRE 2020 preselected for an award: The telomere link between extended fertility and longevity.

  BACKGROUND

• Witz CA, Daftary GS, Doody KJ, Park JK, Seifu Y, Yankov VI, Heiser PW; Menopur in GnRH Antagonist Cycles with Single Embryo Transfer - High Responder (MEGASET-HR) Trial Group. Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection. Fertil Steril. 2020 Aug;114(2):321-330. doi: 10.1016/j.fertnstert.2020.03.029. Epub 2020 May 13.

  PMID: 32416978 BACKGROUND

• Devroey P, Pellicer A, Nyboe Andersen A, Arce JC; Menopur in GnRH Antagonist Cycles with Single Embryo Transfer Trial Group. A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Fertil Steril. 2012 Mar;97(3):561-71. doi: 10.1016/j.fertnstert.2011.12.016. Epub 2012 Jan 13.

  PMID: 22244781 BACKGROUND

• van Wely M, Kwan I, Burt AL, Thomas J, Vail A, Van der Veen F, Al-Inany HG. Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. Cochrane Database Syst Rev. 2011 Feb 16;2011(2):CD005354. doi: 10.1002/14651858.CD005354.pub2.

  PMID: 21328276 BACKGROUND

• Fatemi HM. Assessment of the luteal phase in stimulated and substituted cycles. Facts Views Vis Obgyn. 2009;1(1):30-46. No abstract available.

  PMID: 25478069 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood, cumulus cells and trophectoderm

Study Officials

• Barbara Lawrenz, PhD

  ART Fertility Clinics LLC

  STUDY DIRECTOR

Central Study Contacts

Daniela Nogueira

CONTACT

971504374961; daniela.nogueira@artfertilityclinics.com

Jonalyn DV Edades

CONTACT

+971526408688; jonalyn.ededas@artfertilityclinics.com

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Target Duration: 60 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 13, 2024
• Study Start: July 23, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Locations

AE (1)