Ignite Creation Date:
2025-12-25 @ 1:38 AM
Ignite Modification Date:
2025-12-25 @ 11:54 PM
Study NCT ID:
NCT05370794
Status:
UNKNOWN
Last Update Posted:
2022-11-07
First Post:
2022-04-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Is in Vitro Maturation of Oocytes Influenced by the Origin of Gonadotropins Used in Maturation Medium: is There a Difference in Efficiency When Using Urinary Versus Recombinant Produced Follicle Stimulating Hormone and Human Chorionic Gonadotropin
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'spent medium after IVM, cumulus cells after IVM'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 35}, 'targetDuration': '18 Months', 'patientRegistry': True}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-04-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-05', 'completionDateStruct': {'date': '2023-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-11-04', 'studyFirstSubmitDate': '2022-04-04', 'studyFirstSubmitQcDate': '2022-05-06', 'lastUpdatePostDateStruct': {'date': '2022-11-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-05-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'oocyte maturation', 'timeFrame': 'oocyte maturation is assessed after 30 hours of in vitro maturation', 'description': 'the ability of the oocyte to extrude the first polar body'}], 'secondaryOutcomes': [{'measure': 'Fertilization rate', 'timeFrame': 'the presence of 2 pronuclei is assessed between 18-20 hours after ICSI', 'description': 'the ability of the oocyte to ba activated and form pronuclei'}, {'measure': 'morphologic parameters describing embryo quality per fertilized oocyte', 'timeFrame': 'embryo developmental assessment is performed 3 days after ICSI', 'description': "embryo developmental potential as estimated by morphological characteristics: embryos with 6 cells or more, less than 20% fragmentation, cell size according to division pattern and the absence of multinucleated blastomeres are considered as good quality embryos. As secondary parameters, the presence of vacuoles or granulation in the majority of blastomeres will exclude the embryo from the 'good quality' group regardless of the earlier mentioned parameters."}, {'measure': 'utilization rate', 'timeFrame': 'utilization rate will be established 3 days after ICSI', 'description': 'the embryos of sufficient quality to be vitrified for a deferred embryo transfer'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['In Vitro Maturation of Oocytes']}, 'referencesModule': {'references': [{'pmid': '31111879', 'type': 'BACKGROUND', 'citation': 'Ho VNA, Braam SC, Pham TD, Mol BW, Vuong LN. The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count. Hum Reprod. 2019 Jun 4;34(6):1055-1064. doi: 10.1093/humrep/dez060.'}, {'pmid': '34050448', 'type': 'BACKGROUND', 'citation': 'Cadenas J, Nikiforov D, Pors SE, Zuniga LA, Wakimoto Y, Ghezelayagh Z, Mamsen LS, Kristensen SG, Andersen CY. A threshold concentration of FSH is needed during IVM of ex vivo collected human oocytes. J Assist Reprod Genet. 2021 Jun;38(6):1341-1348. doi: 10.1007/s10815-021-02244-8. Epub 2021 May 28.'}, {'pmid': '17524398', 'type': 'BACKGROUND', 'citation': 'Ge HS, Huang XF, Zhang W, Zhao JZ, Lin JJ, Zhou W. Exposure to human chorionic gonadotropin during in vitro maturation does not improve the maturation rate and developmental potential of immature oocytes from patients with polycystic ovary syndrome. Fertil Steril. 2008 Jan;89(1):98-103. doi: 10.1016/j.fertnstert.2007.02.021. Epub 2007 May 24.'}, {'pmid': '21072289', 'type': 'BACKGROUND', 'citation': 'Nahuis M, van der Veen F, Oosterhuis J, Mol BW, Hompes P, van Wely M. Review of the safety, efficacy, costs and patient acceptability of recombinant follicle-stimulating hormone for injection in assisting ovulation induction in infertile women. Int J Womens Health. 2010 Aug 9;1:205-11. doi: 10.2147/ijwh.s4729.'}, {'pmid': '19778474', 'type': 'BACKGROUND', 'citation': 'Bassett R, Lispi M, Ceccarelli D, Grimaldi L, Mancinelli M, Martelli F, Van Dorsselaer A. Analytical identification of additional impurities in urinary-derived gonadotrophins. Reprod Biomed Online. 2009 Sep;19(3):300-13. doi: 10.1016/s1472-6483(10)60163-0.'}, {'pmid': '29044421', 'type': 'BACKGROUND', 'citation': 'Riccetti L, Klett D, Ayoub MA, Boulo T, Pignatti E, Tagliavini S, Varani M, Trenti T, Nicoli A, Capodanno F, La Sala GB, Reiter E, Simoni M, Casarini L. Heterogeneous hCG and hMG commercial preparations result in different intracellular signalling but induce a similar long-term progesterone response in vitro. Mol Hum Reprod. 2017 Oct 1;23(10):685-697. doi: 10.1093/molehr/gax047.'}]}, 'descriptionModule': {'briefSummary': 'Standard IVM currently contains urinary purified hormones which might contain contaminants possibly affecting maturation of embryo development. The investigators will test if the efficiency in terms of oocyte maturation after IVM of recombinant (without contaminants) is equivalent to urinary gonadotropins. Urinary and recombinant FSH and hCG will be used in equivalent bioactivity as measured in IU/ml and specified by the manufacturer. Sibling oocytes of the patient will be subjected to IVM medium containing urinary or recombinant gonadotropins. Oocyte maturation is the primary outcome, however, fertilization rate and preimplantation embryo development will be investigated.', 'detailedDescription': 'In vitro maturation is a valid option for PCO(S) patients in the daily ART clinic, however maturation and embryologic development are not yet matching the efficiency levels obtained by standard COS treatment (Ho et al. 2019). To further enhance embryo quality after IVM, media and supplements should be efficient, safe and pure. It has been described that a threshold of FSH activity is necessary for maturation in human IVM (Cadenas et al. 2021), but hCG might be redundant (Ge et al 2008).\n\nUntil now, the investigators have been using highly purified urinary derived gonadotropins to supplement IVM media. However in the last decades more recombinant products are available and thoroughly characterized. In ART, both urinary derived and recombinant produced hormones are used to induce multiple follicle growth and ovulation in an ovarian stimulation cycle. Due to the fear of transmis-sion of pathogens (though not yet documented) and of intolerance caused by contaminants, recombinant products are often preferred in the clinic, with no indications of differences in effectiveness and safety (Nahuis 2009). In an in vitro bioassay, contaminating proteins may alter biological re-sponses with undesired effects. uFSH is documented to contain e.g. Insulin-like growth factor binding protein 1 (IGFBP7), that may inhibit oestrogen production, and Eosinophil Derived Neurotoxin (EDN), with known inhibitory effects on mouse oocyte maturation (Bassett 2009). Hence it is important in an in vitro system to use products with the highest purity available.\n\nMoreover the oligosaccharide sialylation is different depending on the production method, altering the acidity and hereby the half-life in the body, but more importantly for an in vitro system, also the receptor binding potency (Bassett 2009, Riccetti 2017).\n\nHence, before changing our standard system for a theoretically better alternative, The investigators need to test the efficiency of recombinant hormones compared to the routinely used urinary hormones in terms of oocyte maturation efficiency in the in vitro maturation system.\n\nPCOS patients eligible for an IVM cycle to treat infertility will be included. Patients will receive a mild ovarian stimulation protocol, identical to our standard IVM care program.\n\nThe investigators will conduct a non-inferiority study for oocyte maturation efficiency with a limit of 10%, significance level of 5% and power of 80%, leading to a sample size of 618 oocytes. The investigators estimate this will be obtained if 35 patients are included in the study.\n\nAfter OR follicle fluids containing COC are filtered over a 70µm mesh filter to eliminate contaminating blood cells and hereby visualizing the COC. The first detected COC will be transferred into a wash droplet of a 4-well dish, the second COC will be kept in the second wash droplet of the 4-well dish, … According to the randomization list, the COC in the first droplet of the 4-well dish will be allocated to the standard or experimental IVM. The randomization list is generated with www.sealedenvelope.com.\n\nMature oocytes will be ferilized by Intracytoplasmic Sperm Injection (ICSI) and fertilization and embryological development will be recorded. Embryos of sufficient quality on day 3 will be vitrified for a deferred vitrified/warmed embryo transfer.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '36 Years', 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'infertility patients', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* PCO(S) patients\n* Anti-Mullerian Hormone ≥ 3.6 ng/mL\n* Basal Antral Follicle Count ≥ 20\n* All ranks of trial\n\nExclusion Criteria:\n\n* Surgically obtained semen sample\n* Grade 3 or 4 endometriosis, minor or major uterine abnormalities\n* Preimplantation Genetic Testing\n* Priming with Letrozole'}, 'identificationModule': {'nctId': 'NCT05370794', 'acronym': 'IVM-FSHhCG', 'briefTitle': 'Is in Vitro Maturation of Oocytes Influenced by the Origin of Gonadotropins Used in Maturation Medium: is There a Difference in Efficiency When Using Urinary Versus Recombinant Produced Follicle Stimulating Hormone and Human Chorionic Gonadotropin', 'organization': {'class': 'OTHER', 'fullName': 'Universitair Ziekenhuis Brussel'}, 'officialTitle': 'Is in Vitro Maturation of Oocytes Influenced by the Origin of Gonadotropins Used in Maturation Medium: is There a Difference in Efficiency When Using Urinary Versus Recombinant Produced Follicle Stimulating Hormone and Human Chorionic Gonadotropin', 'orgStudyIdInfo': {'id': '2021-IVM-FSHhCG'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'standard IVM: urinary purified gonadotropins (uFSH and uhCG)', 'description': 'uhCG = Pregnyl®, 5000IU/ vial, Organon-Merck: final concentration 100mIU/ml + uFSH = Menopur® 75mIU/ml, Ferring: final concentration 75mIU/ml.\n\nAdministered during 30h of in vitro maturation culture'}, {'label': 'Experimental IVM: recombinant gonadotropins (rFSH and rhCG)', 'description': 'rhCG= Ovitrelle®, 250g/0.5ml = 26000IU/ml, Merck-Serono : final concentration 100mIU/ml + rFSH = Gonal F®, 300IU/0.5ml, Merck-Serono: final concentration 75mIU/ml.\n\nAdministered during 30h of in vitro maturation culture', 'interventionNames': ['Drug: rhCG= Ovitrelle®, 250g/0.5ml = 26000IU/ml, Merck-Serono', 'Drug: rFSH = Gonal F®, 300IU/0.5ml, Merck-Serono']}], 'interventions': [{'name': 'rhCG= Ovitrelle®, 250g/0.5ml = 26000IU/ml, Merck-Serono', 'type': 'DRUG', 'description': 'recombinant hCG', 'armGroupLabels': ['Experimental IVM: recombinant gonadotropins (rFSH and rhCG)']}, {'name': 'rFSH = Gonal F®, 300IU/0.5ml, Merck-Serono', 'type': 'DRUG', 'description': 'recombinant FSH', 'armGroupLabels': ['Experimental IVM: recombinant gonadotropins (rFSH and rhCG)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1090', 'city': 'Brussels', 'status': 'RECRUITING', 'country': 'Belgium', 'contacts': [{'name': 'Ingrid Segers, PhD', 'role': 'CONTACT', 'email': 'ingrid.segers@uzbrussel.be', 'phone': '+3224749020'}], 'facility': 'UZ Brussel', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}], 'centralContacts': [{'name': 'Ingrid Segers, PhD', 'role': 'CONTACT', 'email': 'ingrid.segers@uzbrussel.be', 'phone': '+3224776690'}, {'name': 'Elsie Nulens', 'role': 'CONTACT', 'email': 'elsie.nulens@uzbrussel.be', 'phone': '+3224776690'}], 'overallOfficials': [{'name': 'Michel De Vos, MD,PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Universitair Ziekenhuis Brussel'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universitair Ziekenhuis Brussel', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}