Real-world Evidence on Follitropin Delta Individual Dosing

NCT05173597 | Recruiting

• 1 other identifier: Aktenzeichen 21-385
• Study Type: observational
• Target: 850
• Locations: 1 country
• Sites: 1

Brief Summary

As part of the in vitro fertilisation treatment, ovarian stimulation is routinely performed. For this purpose, FSH preparations are used. Follitropin delta is a FSH preparation that is approved for a wide range of applications and is dosed individually according to body weight and serum anti-Müllerian hormone (AMH). Body weight is used to estimate the distribution volume of the glycoprotein FD in the patient and is thus a proxy of exposure. The AMH is used to estimate the ovarian reserve and thus the number of follicles in the ovaries that can be recruited by Follitropin delta stimulation. An algorithm is used for individual dosing. The aim of individual dosing is to reduce the probability of an under or overreaction of the ovaries to FSH therapy. In contrast to phase III registration studies, patients with severe overweight and underweight, as well as very high and very low AMH values and associated disorders of the menstrual cycle and oocyte maturation, are also found in the reality of care. The performance of the dosing algorithm and thus the results of ovarian stimulation in these subgroups of patients have so far been insufficiently investigated in the phase III registration trials. In the present study no statistical hypothesis will be tested. The study is descriptive by design and the analyses are descriptive and exploratory. NIS is chosen in order to explore how the individualized dosing regimen of REKOVELLE® performs in routine clinical practice and to investigate the effectiveness and safety of REKOVELLE® under real-world conditions. This is a monocentric, prospective, non-interventional cohort study conducted in normal care setting in a fertility clinic that will collect information from 850 women undergoing up to two cycles of IVF or ICSI treatment with controlled ovarian stimulation with REKOVELLE®.

Conditions

Infertility; Sterility

Keywords

In-Vitro-Fertilisation; Assisted reproduction; Ovarian Stimulation; Ovarian Hyperstimulation Syndrome

Outcome Measures

Primary Outcomes (1)

• Ovarian response

  Number of cumulus-oocyte-complexes of the individual dosing regimen of follitropin delta for controlled ovarian stimulation for in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) in a cohort of patients from a real-world setting with focus on high body weight.

  2021-2022

Secondary Outcomes (8)

• Overall treatment outcome

  2021-2022

• Change in body weight

  2021-2022

• Incidence of dose changes

  2021-2022

• Intra-individual variation of ovarian response

  2021-2022

• Measurement of correlation of variance of body weight and AMH

  2021-2022

Study Arms (1)

Patients receiving treatment with Follitropin-delta

The included patients are adult women from the routine clinical care settings with indication for ovarian stimulation with follitropin delta in a GnRH-antagonist protocol who are making a first treatment attempt IVF or ICSI. This study is intended to be conducted in non-vulnerable population. No vulnerable subjects will be enrolled in the study.

Drug: Follitropin delta

Interventions

Follitropin delta DRUG

REKOVELLE® (follitropin delta), solution for injection - delivered with an injection pen, ATC code G03GA10, is a recombinant human FSH approved for the controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies such as an in vitro fertilisation or intracytoplasmic sperm injection cycle.

Also known as: REKOVELLE® (follitropin delta)

Patients receiving treatment with Follitropin-delta

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The included patients are adult women from the routine clinical care settings with indication for ovarian stimulation with follitropin delta in a GnRH-antagonist protocol who are making a first treatment attempt IVF or ICSI. This study is intended to be conducted in non-vulnerable population. No vulnerable subjects will be enrolled in the study.

You may qualify if:

• Age ≥18 to ≤ 44 years at enrolment
• Planned stimulation in a fixed or flexible GnRH antagonist protocol
• Planned use of follitropin delta for ovarian stimulation as per SmPC
• Planned IVF or ICSI treatment with ejaculated or cryopreserved male germ cells, autologous or heterologous, with or without planned genetic testing of the oocytes or embryos
• Planned preservation of MII oocytes (fertility preservation)
• Planned triggering of final oocyte maturation with hCG or a GnRH agonist
• Willingness and consent to participate

You may not qualify if:

• Serum AMH within 12 months prior to treatment ≤0.3 ng/ml
• Most recent serum AMH value before start of stimulation older than 12 months
• Serum AMH value not determined in Roche Elecsys immunoassays
• Pre-treatment with a combined oral contraceptive "pill" consisting of ethinyl estradiol and a synthetic progestogen

Sponsors & Collaborators

• University of Luebeck: lead

Study Sites (1)

University of Luebeck

Lübeck, Schleswig-Holstein, 23562, Germany

RECRUITING

Related Publications (18)

• Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Vanderpoel S; International Committee for Monitoring Assisted Reproductive Technology; World Health Organization. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009 Nov;92(5):1520-4. doi: 10.1016/j.fertnstert.2009.09.009. Epub 2009 Oct 14.

  PMID: 19828144 BACKGROUND

• Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015 Mar;103(3):e18-25. doi: 10.1016/j.fertnstert.2014.12.103. Epub 2015 Jan 15.

  PMID: 25597249 BACKGROUND

• Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2012 Aug;98(2):302-7. doi: 10.1016/j.fertnstert.2012.05.032. Epub 2012 Jun 13.

  PMID: 22698637 BACKGROUND

• Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007 Jun;22(6):1506-12. doi: 10.1093/humrep/dem046. Epub 2007 Mar 21.

  PMID: 17376819 BACKGROUND

• Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356. doi: 10.1371/journal.pmed.1001356. Epub 2012 Dec 18.

  PMID: 23271957 BACKGROUND

• Arce JC, Andersen AN, Fernandez-Sanchez M, Visnova H, Bosch E, Garcia-Velasco JA, Barri P, de Sutter P, Klein BM, Fauser BC. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimullerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014 Dec;102(6):1633-40.e5. doi: 10.1016/j.fertnstert.2014.08.013. Epub 2014 Sep 23.

  PMID: 25256937 BACKGROUND

• Practice Committee of American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil Steril. 2008 Nov;90(5 Suppl):S188-93. doi: 10.1016/j.fertnstert.2008.08.034.

  PMID: 19007627 BACKGROUND

• Kupka MS, Ferraretti AP, de Mouzon J, Erb K, D'Hooghe T, Castilla JA, Calhaz-Jorge C, De Geyter C, Goossens V; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014 Oct 10;29(10):2099-113. doi: 10.1093/humrep/deu175. Epub 2014 Jul 27.

  PMID: 25069504 BACKGROUND

• Klemetti R, Sevon T, Gissler M, Hemminki E. Complications of IVF and ovulation induction. Hum Reprod. 2005 Dec;20(12):3293-300. doi: 10.1093/humrep/dei253. Epub 2005 Aug 26.

  PMID: 16126753 BACKGROUND

• La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2014 Jan-Feb;20(1):124-40. doi: 10.1093/humupd/dmt037. Epub 2013 Sep 29.

  PMID: 24077980 BACKGROUND

• Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006 Nov-Dec;12(6):685-718. doi: 10.1093/humupd/dml034. Epub 2006 Aug 4.

  PMID: 16891297 BACKGROUND

• Nelson SM. Biomarkers of ovarian response: current and future applications. Fertil Steril. 2013 Mar 15;99(4):963-9. doi: 10.1016/j.fertnstert.2012.11.051. Epub 2013 Jan 8.

  PMID: 23312225 BACKGROUND

• La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30.

  PMID: 19793843 BACKGROUND

• Anckaert E, Smitz J, Schiettecatte J, Klein BM, Arce JC. The value of anti-Mullerian hormone measurement in the long GnRH agonist protocol: association with ovarian response and gonadotrophin-dose adjustments. Hum Reprod. 2012 Jun;27(6):1829-39. doi: 10.1093/humrep/des101. Epub 2012 Apr 3.

  PMID: 22473395 BACKGROUND

• Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014 Sep-Oct;20(5):688-701. doi: 10.1093/humupd/dmu020. Epub 2014 May 12.

  PMID: 24821925 BACKGROUND

• La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-Mullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006 Dec;21(12):3103-7. doi: 10.1093/humrep/del291. Epub 2006 Aug 21.

  PMID: 16923748 BACKGROUND

• Gassner D, Jung R. First fully automated immunoassay for anti-Mullerian hormone. Clin Chem Lab Med. 2014 Aug;52(8):1143-52. doi: 10.1515/cclm-2014-0022.

  PMID: 24622790 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Infertility; Ovarian Hyperstimulation Syndrome

Interventions

follitropin delta

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gonadal Disorders; Endocrine System Diseases

Central Study Contacts

Georg Griesinger, MD

CONTACT

+49 451-500-41950; georg.griesinger@uni-luebeck.de

Tanja Eggersmann, MD

CONTACT

+49 451-500-41950; TanjaKristina.Eggersmann@uksh.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: December 30, 2021
• Study Start: December 8, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Locations

DE (1)