Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy

NCT04948658 | Recruiting

• 2 other identifiers: 10000106000106-CH
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Turner 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. Objective: To 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. Eligibility: Individuals 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 Design: Participants will be screened with a medical history. Participants 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. Participants 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. Participants 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. A piece of the gonads (no more than 20%) will be used for research Travel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed. Participants 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. Participation will last 30 years.

Conditions

Ovarian Disfunction; Variations in Sex Characteristics; Differences in Sex Development; Turner Syndrome; Post-menarcheal Adolescents; Galactosemia

Keywords

OVARIAN FUNCTION; Natural History; follicle loss; Variations in Sex Characteristics; Differences in Sex Development

Outcome Measures

Primary Outcomes (2)

• Single cell/nucleus RNA sequencing

  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.

  before and after cryopreservation

• Tissue for research

  initial evaluation of number and quality of follicles before and after cryopreservation

  before and after cryopreservation

Secondary Outcomes (5)

• Evaluate gonadal tissue

  before and after cryopreservation

• Evaluate changes in single cell/nucleus RNA sequencing

  before and after cryopreservation

• Compare hormone levels

  before and after cryopreservation

• density and quality of follicles in the ovaries

  before and after cryopreservation

• Correlation of follicle density and quality with markers such as age, AMH, condition.

  before and after cryopreservation

Study Arms (6)

Adolescents with DOR

Adolescents with diminished ovarian reserve (DOR) who respond poorly to ovarian stimulation for egg freezing.

Adolescents with POI

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.

Individuals receiving high-risk gonadotoxic therapy

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.

Individuals with variations in sex characteristics (or differences in sex development, DSD)

Individuals with variations in sex characteristics (or differences in sex development, DSD) who undergo gonadectomy for clinical indications.

Turner Syndrome and galactosemia

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).

Turner Syndrome with Y material

Children and adolescents who have Turner syndrome with Y material and undergo prophylactic gonadectomy.

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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 (2-24) 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.

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years whose families seek to store ovarian tissue for possible future use.
• Individuals with galactosemia (age 2-21)
• Adolescent 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.
• Children or adolescents aged 2-24 years old who have diminished ovarian reserve based on laboratory findings or who respond poorly to ovarian stimulation for egg freezing.
• Individuals 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.
• 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.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability of subject, parents, or guardian to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Individuals older than 7 years with psychological, psychiatric, or other conditions which prevent giving fully informed consent or assent.
• 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.
• Individuals whose underlying medical condition significantly increases their risk of complications from anesthesia and surgery.
• Females with POI due to chemotherapy or radiation treatment
• Pregnancy or lactation
• Individuals with VSC who choose to retain gonads after clinical consulting.
• Individuals with Turner Syndrome who have an undetectable AMH based on testing laboratory reference range.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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: 30098684 BACKGROUND

• 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: 28739117 BACKGROUND

• 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.

  PMID: 31594631 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Turner Syndrome; Galactosemias

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Veronica Gomez-Lobo, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veronica Gomez-Lobo, M.D.

CONTACT

(301) 435-7567; veronica.gomez-lobo@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 2, 2021
• Study Start: September 13, 2021
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04-29

Locations

US (1)