Cumulative Pregnancy Rate With Lower and Higher Gonadotropin Dose During IVF Among Poor Responders

NCT05103228 | Completed Results

• 1 other identifier: 52007-13/2021
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Controlled ovarian hyperstimulation (COH) is an important step during in vitro fertilization (IVF). Its aim optimally is to recruit 10-15 oocytes. When deciding on the actual treatment, different stimulation protocols, various stimulating agents and wide range of gonadotropin dose can one choose from. Prior to the decision on the actual stimulation protocol and gonadotropin (Gn) dose the patient's expected response to stimulation is assessed primarily using ovarian reserve markers. Most medications used during stimulation exert their effect in a dose-dependent manner hence with a higher Gn dose one would expect a better response, more oocytes. More oocytes could translate into more embryos and potentially a higher pregnancy rate. The currently available evidence however does not support this practice as randomized controlled trials (RCT) have failed to show that the use of higher Gn dose results in higher pregnancy, live-birth rates. These studies however identified patients based on different criteria, compared different stimulation protocols and various Gn doses. There are only two RCTs that compared cumulative live birth rates (fresh + frozen embryo transfers) and they identified poor responders based on different criteria and used different drug regimens. Therefore, the aim of our study is to compare cumulative IVF clinical pregnancy rates using a lower and a higher gonadotropin dose among poor responders identified based on universally accepted criteria.

Conditions

Infertility; Ovarian Dysfunction

Keywords

gonadotropin; follitropin alpha; follitropin delta; high-dose gonadotropin; clinical pregnancy; cumulative pregnancy rate

Outcome Measures

Primary Outcomes (1)

• Cumulative Clinical Pregnancy Rate

  an ultrasound confirmation of an intrauterine gestational sac with an embryo with detectable heartbeat in it after the fresh + if available frozen embryo transfer treatments

  18 months

Secondary Outcomes (2)

• Live Birth Rate

  12 months

• Cumulative Live Birth Rate

  12 months

Study Arms (2)

Lower gonadotropin dose stimulation

EXPERIMENTAL

Low-dose group: * 150 IU follitropin alpha + 75 IU highly purified human menopausal gonadotropin (hpHMG) * 10 mcg follitropin delta + 75 IU hpHMG

Drug: Follitropin Alfa; Drug: Follitropin delta; Drug: human menopausal gonadotropin

Higher gonadotropin dose stimulation

EXPERIMENTAL

High-dose group: * 225 IU follitropin alpha + 150 IU highly purified human menopausal gonadotropin (hpHMG) * 15 mcg follitropin delta + 150 IU hpHMG

Drug: Follitropin Alfa; Drug: Follitropin delta; Drug: human menopausal gonadotropin

Interventions

Follitropin Alfa DRUG

lower dose gonadotropin (follitropin alpha/ follitropin delta + hpHMG) vs. higher dose stimulation (Follitropin alpha/delta + hpHMG)

Also known as: Ovaleap (Theramex Ireland Limited), Bemfola (Richter Gedeon Nyrt., Hungary), Gonal F (Merck Europe B.V.)

Higher gonadotropin dose stimulation; Lower gonadotropin dose stimulation

Follitropin delta DRUG

lower dose gonadotropin (follitropin alpha/ follitropin delta + hpHMG) vs. higher dose stimulation (Follitropin alpha/delta + hpHMG)

Also known as: Rekovelle (Ferring Pharmaceuticals A/S, Denmark)

Higher gonadotropin dose stimulation; Lower gonadotropin dose stimulation

human menopausal gonadotropin DRUG

lower dose gonadotropin (follitropin alpha/ follitropin delta + hpHMG) vs. higher dose stimulation (Follitropin alpha/delta + hpHMG)

Also known as: Menopur (Ferring Pharmaceuticals A/S, Denmark)

Higher gonadotropin dose stimulation; Lower gonadotropin dose stimulation

Eligibility Criteria

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

You may qualify if:

• Expected poor responder based on:
• AMH: 0.3-1.2 ng/ml or AFC \<5,
• AMH\>1.2 ng/ml or AFC≥5 but the retrieval of ≤ 4 oocytes during previous IVF treatment.
• motile sperm with normal morphology obtained from the ejaculate of testicular biopsy
• no more than 3 previous failed IVF cycles (if the patient had 2 or more previous cycles cancelled for poor response she cannot be included)
• BMI: 18-35 kg/m2
• regular 24-35 day cycles
• intact uterine cavity
• indication for in vitro fertilisation treatment (tubal factor, male factor, low ovarian reserve, endometriosis, unexplained infertility)
• age 18-421 yrs

You may not qualify if:

• presence of hydrosalpinx
• positive HIV, hepatitis B, C screening tests
• planned preimplantation genetic testing of the embryos
• planned elective cryopreservation
• lack of consent

Sponsors & Collaborators

• Peter Kovacs MD: lead

Study Sites (1)

Dunamenti REK Reprodukciós Központ

Budapest, 1125, Hungary

Location

Related Publications (20)

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  PMID: 24077980 RESULT

• Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org; Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2020 Dec;114(6):1151-1157. doi: 10.1016/j.fertnstert.2020.09.134.

  PMID: 33280722 RESULT

• Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.

  PMID: 21505041 RESULT

• Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number); Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, Esteves SC, Fischer R, Galliano D, Polyzos NP, Sunkara SK, Ubaldi FM, Humaidan P. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016 Jun;105(6):1452-3. doi: 10.1016/j.fertnstert.2016.02.005. Epub 2016 Feb 26. No abstract available.

  PMID: 26921622 RESULT

• Leijdekkers JA, Torrance HL, Schouten NE, van Tilborg TC, Oudshoorn SC, Mol BWJ, Eijkemans MJC, Broekmans FJM. Individualized ovarian stimulation in IVF/ICSI treatment: it is time to stop using high FSH doses in predicted low responders. Hum Reprod. 2020 Sep 1;35(9):1954-1963. doi: 10.1093/humrep/dez184.

  PMID: 31838515 RESULT

• van Tilborg TC, Torrance HL, Oudshoorn SC, Eijkemans MJC, Koks CAM, Verhoeve HR, Nap AW, Scheffer GJ, Manger AP, Schoot BC, Sluijmer AV, Verhoeff A, Groen H, Laven JSE, Mol BWJ, Broekmans FJM; OPTIMIST study group. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder. Hum Reprod. 2017 Dec 1;32(12):2496-2505. doi: 10.1093/humrep/dex318.

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• Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org. Comparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline. Fertil Steril. 2018 Jun;109(6):993-999. doi: 10.1016/j.fertnstert.2018.03.019.

  PMID: 29935660 RESULT

• Arce JC, Larsson P, Garcia-Velasco JA. Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa. Reprod Biomed Online. 2020 Oct;41(4):616-622. doi: 10.1016/j.rbmo.2020.07.006. Epub 2020 Jul 15.

  PMID: 32819842 RESULT

• Nyboe Andersen A, Nelson SM, Fauser BC, Garcia-Velasco JA, Klein BM, Arce JC; ESTHER-1 study group. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017 Feb;107(2):387-396.e4. doi: 10.1016/j.fertnstert.2016.10.033. Epub 2016 Nov 29.

  PMID: 27912901 RESULT

• Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, Arce JC; ESTHER-2 Study Group. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial. Reprod Biomed Online. 2019 Feb;38(2):195-205. doi: 10.1016/j.rbmo.2018.10.012. Epub 2018 Dec 14.

  PMID: 30594482 RESULT

• Ishihara O, Klein BM, Arce JC; Japanese Follitropin Delta Phase 2 Trial Group. Randomized, assessor-blind, antimullerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta. Fertil Steril. 2021 Jun;115(6):1478-1486. doi: 10.1016/j.fertnstert.2020.10.059. Epub 2020 Dec 4.

  PMID: 33272623 RESULT

MeSH Terms

Conditions

Infertility

Interventions

follitropin alfa; follitropin delta; Menotropins

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr Peter Kovacs
• Organization: Dunamenti REK IVF Center (former Kaali Institute)

peterkovacs1970@hotmail.com

+3612022802

Study Officials

• Peter Kovacs, MD

  Dunamenti REK Istenhegyi IVF Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 2, 2021
• Study Start: December 2, 2021
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)