Ignite Creation Date:
2025-12-25 @ 12:05 AM
Ignite Modification Date:
2025-12-25 @ 10:04 PM
Study NCT ID:
NCT04948658
Status:
RECRUITING
Last Update Posted:
2025-11-26
First Post:
2021-07-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D014424', 'term': 'Turner Syndrome'}, {'id': 'D005693', 'term': 'Galactosemias'}], 'ancestors': [{'id': 'D006059', 'term': 'Gonadal Dysgenesis'}, {'id': 'D012734', 'term': 'Disorders of Sex Development'}, {'id': 'D014564', 'term': 'Urogenital Abnormalities'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D058533', 'term': 'Sex Chromosome Disorders of Sex Development'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D006330', 'term': 'Heart Defects, Congenital'}, {'id': 'D018376', 'term': 'Cardiovascular Abnormalities'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D025064', 'term': 'Sex Chromosome Disorders'}, {'id': 'D025063', 'term': 'Chromosome Disorders'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D002239', 'term': 'Carbohydrate Metabolism, Inborn Errors'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-09-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11-24', 'completionDateStruct': {'date': '2030-07-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-25', 'studyFirstSubmitDate': '2021-07-01', 'studyFirstSubmitQcDate': '2021-07-01', 'lastUpdatePostDateStruct': {'date': '2025-11-26', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2021-07-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-07-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Single cell/nucleus RNA sequencing', 'timeFrame': 'before and after cryopreservation', 'description': 'Single cell/nucleus RNA sequencing on fresh compared to frozen and thawed tissue. This will assess what transcription changed occur due to the freezing process.'}, {'measure': 'Tissue for research', 'timeFrame': 'before and after cryopreservation', 'description': 'initial evaluation of number and quality of follicles before and after cryopreservation'}], 'secondaryOutcomes': [{'measure': 'Evaluate gonadal tissue', 'timeFrame': 'before and after cryopreservation', 'description': 'The ability to safely offer a fertility preservation option to individuals who are at high risk such as POI, DOR and VSC.'}, {'measure': 'Evaluate changes in single cell/nucleus RNA sequencing', 'timeFrame': 'before and after cryopreservation', 'description': 'Evaluate changes in single cell/nucleus RNA sequencing in tissue before and after treatment with primordial follicle inhibitors and activators.'}, {'measure': 'Compare hormone levels', 'timeFrame': 'before and after cryopreservation', 'description': 'Comparison of hormone levels such as AMH, FSH, LH, and Estradiol between patients and controls.'}, {'measure': 'density and quality of follicles in the ovaries', 'timeFrame': 'before and after cryopreservation', 'description': 'Evaluation of density and quality of follicles in the ovaries of girls with Turner syndrome, galactosemia and post-menarcheal adolescent with premature ovarian insufficiency before and after cryopreservation and thawing'}, {'measure': 'Correlation of follicle density and quality with markers such as age, AMH, condition.', 'timeFrame': 'before and after cryopreservation', 'description': 'Correlation of follicle density and quality with markers such as age, AMH, condition.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['OVARIAN FUNCTION', 'Natural History', 'follicle loss', 'Variations in Sex Characteristics', 'Differences in Sex Development'], 'conditions': ['Turner Syndrome', 'Post-menarcheal Adolescents', 'Ovarian Disfunction', 'Galactosemia', 'Variations in Sex Characteristics', 'Differences in Sex Development']}, 'referencesModule': {'references': [{'pmid': '30098684', 'type': 'BACKGROUND', 'citation': 'Ethics Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org. Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion. Fertil Steril. 2018 Aug;110(3):380-386. doi: 10.1016/j.fertnstert.2018.05.034.'}, {'pmid': '28739117', 'type': 'BACKGROUND', 'citation': 'Martinez F; International Society for Fertility Preservation-ESHRE-ASRM Expert Working Group. Update on fertility preservation from the Barcelona International Society for Fertility Preservation-ESHRE-ASRM 2015 expert meeting: indications, results and future perspectives. Fertil Steril. 2017 Sep;108(3):407-415.e11. doi: 10.1016/j.fertnstert.2017.05.024. Epub 2017 Jul 21.'}, {'pmid': '31594631', 'type': 'BACKGROUND', 'citation': 'Andersen ST, Pors SE, Poulsen LC, Colmorn LB, Macklon KT, Ernst E, Humaidan P, Andersen CY, Kristensen SG. Ovarian stimulation and assisted reproductive technology outcomes in women transplanted with cryopreserved ovarian tissue: a systematic review. Fertil Steril. 2019 Nov;112(5):908-921. doi: 10.1016/j.fertnstert.2019.07.008. Epub 2019 Oct 6.'}], 'seeAlsoLinks': [{'url': 'https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000106-CH.html', 'label': 'NIH Clinical Center Detailed Web Page'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\nTurner Syndrome, galactosemia, and premature ovarian insufficiency are all conditions that may make it very hard or impossible for a person to become pregnant and have their own child. Researchers want to learn more about why this happens and if freezing Gonadal tissue allows for fertility preservation.\n\nObjective:\n\nTo find out why people with certain conditions have can have premature ovarian insufficiency (POI or early menopause) and individuals with variations in sex characteristics have trouble getting pregnant and if freezing the gonads tissue from them will help to have their own child in the future.\n\nEligibility:\n\nIndividuals aged 2-21 who have Turner Syndrome or galactosemia. Also, females aged 13-21 with premature ovarian insufficiency, individuals with variations in sex characteristics, and individuals 2-35 receiving high-risk gonadotoxic therapy\n\nDesign:\n\nParticipants will be screened with a medical history.\n\nParticipants may have a physical exam and blood tests. Their body measurements may be taken. These include weight, height, arm span, skin fold, and sitting height. They may fill out surveys about their quality of life, body image, and health.\n\nParticipants may have a transabdominal pelvic ultrasound. A probe will be placed on their belly and will take pictures of the organs in the pelvis. They may have a transvaginal pelvic ultrasound performed while asleep in the operating room if needed.\n\nParticipants may have surgery to remove an gonads and skin biopsy. The removed tissue will be frozen and stored. The tissue will have to be stored for many years. NIH will pay to store the tissue for 1 year. After that, participants will have to pay for storage.\n\nA piece of the gonads (no more than 20%) will be used for research\n\nTravel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed.\n\nParticipants will have a checkup 6 weeks after surgery one or more follow-up visits 6-18 months after surgery. They may have phone follow-up every 12-24 months after surgery.\n\nParticipation will last 30 years.', 'detailedDescription': 'Study Description:\n\nGonadal tissue cryopreservation will be evaluated in individuals with Turner Syndrome, galactosemia, post-menarcheal adolescents with recent premature ovarian insufficiency, and children/adolescents conditions associated with POI and with diminished ovarian reserve (DOR) who have contraindication to ovarian stimulation as well as those with diminished ovarian reserve who did not respond to ovarian stimulation, and individuals with variations in sex characteristics (VSD or differences in sex development, DSD) including those with Turner syndrome with Y chromosome material and those with conditions that require high risk gonadotoxic therapy.\n\nObjectives:\n\nPrimary Objectives: After initial evaluation of number and quality of follicles/gametes, the remaining tissue will be utilized to perform research regarding mechanisms of follicle/gametes loss in the included conditions.\n\na. We will perform next generation sequencing on the tissue collected from study participants and ovaries from cadaveric organ donors on cardiopulmonary support. Additionally, some ovarian tissue from patients undergoing gonadotoxic therapy will function as controls.\n\nHypothesis: next generation sequencing from tissue obtained from gonads in individuals with these conditions will differ significantly from that of controls. Such differences may allow for further hypothesis development regarding the underlying mechanism of follicle loss and/or dysfunction in individuals with these conditions.\n\nSecondary Objective: This protocol is designed to evaluate the feasibility (meaning a reasonable expectation of future fertility based on the anatomy, histology, and physiology of fresh gonadal tissue as well as the effects after freezing and thawing) of gonadal tissue cryopreservation (GTC) for fertility preservation in children with increased risk of loss of gonadal function due to underlying genetic conditions including Turner syndrome or galactosemia and post-menarcheal adolescents with a recent development of premature ovarian insufficiency (POI) or children/adolescents with conditions associated with POI and presenting with diminished ovarian reserve (based on laboratory findings of low AMH (\\<1.0 ng/mL) and/or mildly elevated FSH (\\>10 U/L) or those who do not respond to ovarian stimulation for oocyte cryopreservation due to lower follicle counts) or individuals with variations in sex characteristics.\n\n1. The feasibility GTC as a fertility preservation option in these individuals will be evaluated through evaluation of number and quality of follicles/gametes found in the tissue prior to freezing and after thawing.\n2. Lack of follicles/gametes in the gonadal tissue will confirm that GTC is not a viable option for fertility preservation for these populations.\n3. An attempt to correlate laboratory and imaging markers with follicle/gamete presence and number will be made.\n\nb. Hypothesis: Young individuals with Turner syndrome, variations of sex characteristics, classic galactosemia and adolescents with recent POI, and children/adolescents with underlying conditions associated with POI presenting with DOR harbor populations of follicles/gametes which may be preserved through gonadal tissue cryopreservation for future fertility. There will be a variety of follicular findings which will correlate with patient s anti-Mullerian hormone (AMH), age and underlying condition.\n\nc. Depending on their underlying condition, individuals with VSC will have gametes (follicles and/or spermatogonia).\n\nd. Loss of follicles with cryopreservation and thawing will be similar to that of non-affected individuals.\n\nTertiary Objectives:\n\nResearch regarding inhibition and activation of follicles within the tissue will be undertaken.\n\n1\\. Tissue will be treated with known inhibitors and activators and next generation sequencing will be performed in order to assess gene expression before and after treatment.\n\nHypothesis: Primordial follicles within gonadal tissue in individuals with these conditions may be inhibited from activating. Such techniques may allow for a decrease in follicle loss with freezing and thawing as well as possible future development of novel treatments to prevent accelerated follicle loss in individuals and adolescent affected by these conditions. Promoting follicle activation prior to re-implantation of the tissue may improve the possibility of achieving pregnancy after tissue re-implantation\n\nEndpoints:\n\nPrimary Endpoints:\n\n1. Tissue for research: Next generation sequencing will be performed on tissues of affected individuals and compared to age matched controls: patients who undergo GTC for solid organ tumors far from the reproductive system or cadaveric organ donors on cardiopulmonary support. This will allow for specific cellular type comparisons within the ovary and exploratory research regarding possible mechanisms of follicle loss in these populations.\n2. Next generation sequencing on fresh compared to frozen and thawed tissue. This will assess what transcription changed occur due to the freezing process.\n\nSecondary Endpoint:\n\n1. Evaluation of density and quality of follicles/gametes in the gonads of individuals with increased risk of loss of gonadal function due to underlying genetic conditions including Turner syndrome or galactosemia and post-menarcheal adolescents with a recent development of premature ovarian insufficiency (POI) or children/adolescents with conditions associated with POI and presenting with diminished ovarian reserve (based on laboratory findings of low AMH (\\<1.1 ng/mL) and mildly elevated FSH (10-25 U/L) or those who do not respond to ovarian stimulation for oocyte cryopreservation due to lower follicle counts) or individuals with variations in sex characteristics.\n2. Correlation of follicle/gamete density and quality with markers such as age, AMH, condition.\n3. Comparison of hormone levels such as AMH, FSH, LH, and Estradiol between patients and controls.\n4. Long term data regarding surgical complications\n\nTertiary Endpoint:\n\n-Evaluate changes in single next generation sequencing in tissue before and after treatment with primordial follicle inhibitors and activators. The remaining tissue will be cryopreserved for future experiments.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '35 Years', 'minimumAge': '2 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years, who have not previously demonstrated signs of premature ovarian insufficiency (FSH\\>25 IU/L) and have detectable anti-Mullerian hormone (AMH). Individuals with classic galactosemia age 2-21. Individuals with Turner Syndrome with Y chromosome material who undergo prophylactic gonadectomy. Adolescent females aged 13 to 21 years old who have undergone menarche and are subsequently diagnosed with premature ovarian insufficiency with their last menstrual period having occurred within 2 years of presentation. Children and Adolescents (2-21) with diminished ovarian reserve who have contraindication to ovarian stimulation as well as those with diminished ovarian reserve who did not respond to ovarian stimulation. Individuals with variations in sex characteristics (or differences in sex development, DSD) who undergo gonadectomy for clinical indications.', 'healthyVolunteers': False, 'eligibilityCriteria': '* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n-Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years whose families seek to store ovarian tissue for possible future use.\n\nOr\n\nIndividuals with galactosemia (age 2-21)\n\nOr\n\nAdolescent females up to age 21 years old, who have undergone menarche and are subsequently diagnosed with premature ovarian insufficiency and their last menstrual period occurred within 2 years of presentation. Diagnosis of POI is based on 2 elevated FSH concentrations obtained over 1 month apart.\n\nOr\n\nChildren or adolescents who have diminished ovarian reserve based on laboratory findings or who respond poorly to ovarian stimulation for egg freezing.\n\nOr\n\nIndividuals with variations in sex characteristics (or differences in sex development, DSD) including Turner syndrome with Y chromosome material who undergo prophylactic gonadectomy for clinical indications.\n\nOr\n\nIndividuals (2-35 years) receiving high-risk gonadotoxic therapy at the NIH Clinical Center who are at high risk for developing premature ovarian insufficiency and infertility.\n\n* Stated willingness to comply with all study procedures and availability for the duration of the study.\n* Ability of subject, parents, or guardian to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Individuals older than 7 years with psychological, psychiatric, or other conditions which prevent giving fully informed consent or assent.\n* Individuals with a pelvic mass tumor noted on pre-operative ultrasound, will undergo usual care for the underlying condition and will not undergo oophorectomy for ovarian tissue cryopreservation.\n* Individuals whose underlying medical condition significantly increases their risk of complications from anesthesia and surgery.\n* Females with POI due to chemotherapy or radiation treatment\n* Pregnancy or lactation\n* Individuals with VSC who choose to retain gonads after clinical consulting.\n* Individuals with Turner Syndrome who have an undetectable AMH based on testing laboratory reference range.'}, 'identificationModule': {'nctId': 'NCT04948658', 'briefTitle': 'Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy', 'orgStudyIdInfo': {'id': '10000106'}, 'secondaryIdInfos': [{'id': '000106-CH'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Adolescents with DOR', 'description': 'Adolescents with diminished ovarian reserve (DOR) who respond poorly to ovarian stimulation for egg freezing.'}, {'label': 'Adolescents with POI', 'description': 'Adolescent females up to age 21 years old, who have undergone menarche and are subsequently diagnosed with POI and their last menstrual period occurred within 2 years of presentation.'}, {'label': 'Individuals receiving high-risk gonadotoxic therapy', 'description': 'Individuals (2-35 years) receiving high-risk gonadotoxic therapy at the NIH Clinical Center who are at high risk for developing premature ovarian insufficiency and infertility.'}, {'label': 'Individuals with variations in sex characteristics (or differences in sex development, DSD)', 'description': 'Individuals with variations in sex characteristics (or differences in sex development, DSD) who undergo gonadectomy for clinical indications.'}, {'label': 'Turner Syndrome and galactosemia', 'description': 'Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years, who have not previously demonstrated signs of premature ovarian insufficiency (FSH\\>25 IU/L).'}, {'label': 'Turner Syndrome with Y material', 'description': 'Children and adolescents who have Turner syndrome with Y material and undergo prophylactic gonadectomy.'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)', 'role': 'CONTACT', 'email': 'prpl@cc.nih.gov', 'phone': '800-411-1222', 'phoneExt': 'TTY8664111010'}], 'facility': 'National Institutes of Health Clinical Center', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'centralContacts': [{'name': 'Veronica Gomez-Lobo, M.D.', 'role': 'CONTACT', 'email': 'veronica.gomez-lobo@nih.gov', 'phone': '(301) 435-7567'}], 'overallOfficials': [{'name': 'Veronica Gomez-Lobo, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'We are trying to figure out if we want to share IPD.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}