Embryo QUAlity in Ovarian Stimulation With hMG.

Official title

The Impact of Ovarian Stimulation With hMG on Embryo Quality in Advanced Age Women. A Randomized Controlled Trial

Overview

Ovarian stimulation (OS) is a key component of IVF, aimed at increasing oocyte yield and improving embryo development potential. While early protocols relied solely on FSH, newer approaches incorporate hMG and LH-based stimulation, allowing more individualized treatments for specific patient populations. Evidence suggests that hMG and recombinant FSH (rFSH) have comparable effectiveness in stimulation outcomes, and current guidelines support the use of both. However, the impact of different gonadotropins on embryo quality remains unclear, with mixed findings across protocols. Given the increasing use of combined rFSH and hMG and the limited data in PPOS protocols, this study proposes a randomized controlled trial to compare embryo quality between two different rFSH-hMG dosing strategies.

Interventions

• Drug 10 mcg of follitropin-delta + 150 of hMG
  On day 2 or 3 of the menstrual cycle, daily injections of 10 mcg of Rekovelle + 150 IU of Menopur (Stimulation Day 1) will be administered. Scan controls and blood exams will be performed on stimulation days 6, 8 and on trigger day. Further blood exams will add according to clinical needs. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.
• Drug 5 mcg of follitropin-delta + 225 of hMG
  On day 2 or 3 of the menstrual cycle, daily injections of 5 mcg of Rekovelle + 225 IU of Menopur (Stimulation Day 1) will be administered. Scan controls and blood exams will be performed on stimulation days 6, 8 and on trigger day. Further blood exams will add according to clinical needs. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.

Primary outcome measures

• Good quality blastocysts [Time frame: From Day 5 to Day 7 after insemination]

Secondary outcome measures (12)

• Total Gonadotropin Dose Administered [Time frame: From initiation of ovarian stimulation until day of trigger (up to 15 days)]
• Duration of Ovarian Stimulation [Time frame: From first day of stimulation until trigger day (up to 15days)]
• Total Number of Oocytes Retrieved [Time frame: At oocyte retrieval]
• Number of mature oocytes (MII) retrieved [Time frame: At oocyte retrieval]
• Serum levels of estradiol (E2) [Time frame: At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days)]
• Serum levels of progesterone (P4) [Time frame: At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days)]
• Serum levels of follicle-stimulating hormone (FSH) [Time frame: At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days)]
• Serum levels of luteinizing hormone (LH) [Time frame: At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days)]
• Follicle-to-Oocyte Index (FOI) [Time frame: From baseline AFC assessment to oocyte retrieval]
• Follicular Output RaTe (FORT) [Time frame: From baseline AFC assessment to trigger day]
• Cycle cancellation rate [Time frame: From start of stimulation to planned oocyte retrieval]
• Reason for cycle cancellation [Time frame: At time of cycle cancellation]

Eligibility criteria

Inclusion criteria

• Undergoing preimplantation genetic screening cycles
• AMH 0.5 - 3.5 ng/ml or AFC 5-20 (results of up to one year will be valid)
• BMI 18.5 - 30 Kg/m2
• Normal karyotypes in both partners

Exclusion criteria

• Previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol), according to Bologna criteria
• Severe male factor requiring TESE (testicular sperm extraction)
• Administration of any other drug potentially interfering with the treatment
• Contraindication for hormonal treatment
• Recent history of severe disease requiring regular treatment (clinically significant concurrent medical condition that could compromise subject safety or interfere with the trial assessment)
• Monogenic disease to be detected with PGT-M
• Biochemical and/or ultrasonographic evidence of polycystic ovarian syndrome
• Endocrinological and/or autoimmune disorders

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 4 centers

• Dexeus Mujer Sabadell — Sabadell
• Dexeus Mujer Sant Cugat — Sant Cugat del Vallès
• Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus — Barcelona
• Dexeus Mujer Tarragona — Tarragona

Publications

• 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
• Racca A, Rodriguez I, Garcia S, Arroyo G, Polyzos NP. Double versus single stimulation in young low prognosis patients followed by a fresh embryo transfer: a randomized controlled trial (DUOSTIM-fresh). Hum Reprod. 2024 Jun 6:deae104. doi: 10.1093/humrep/deae104. Online ahead of print. PMID 38845190
• Veiga A, Sandalinas M, Benkhalifa M, Boada M, Carrera M, Santalo J, Barri PN, Menezo Y. Laser blastocyst biopsy for preimplantation diagnosis in the human. Zygote. 1997 Nov;5(4):351-4. doi: 10.1017/s0967199400003920. PMID 9563682
• 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):321-33 PMID 32416978
• Ziebe S, Lundin K, Janssens R, Helmgaard L, Arce JC; MERIT (Menotrophin vs Recombinant FSH in vitro Fertilisation Trial) Group. Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF. Hum Reprod. 2007 Sep;22(9):2404-13. doi: 10.1093/humrep/dem221. Epub 2007 Jul 19. PMID 17640944
• Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006 Dec;21(12):3217-27. doi: 10.1093/humrep/del284. Epub 2006 Jul 27. PMID 16873892
• Boada M, Carrera M, De La Iglesia C, Sandalinas M, Barri PN, Veiga A. Successful use of a laser for human embryo biopsy in preimplantation genetic diagnosis: report of two cases. J Assist Reprod Genet. 1998 May;15(5):302-7. doi: 10.1023/a:1022548612107. PMID 9604764
• Chapon RCB, Genro VK, Souza CAB, Cunha-Filho JS. Randomized controlled trial comparing embryonic quality in rFSH versus hMG in the IVF protocol with GnRH Antagonist. JBRA Assist Reprod. 2021 Feb 2;25(1):131-135. doi: 10.5935/1518-0557.20200064. PMID 33118716

Identifiers

NCT: NCT07691073 · FSD-QUA-2025-27 · 2025-524761-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗