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

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

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age2-35

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

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years whose families seek to store ovarian tissue for possible future use.

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.

Disqualifiers

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

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

200 Participants

are grouped into 6 trial groups

Trial groups

See each trial group below.

Group A: Adolescents with DOR

Group B: Adolescents with POI

Group C: Individuals receiving high-risk gonadotoxic therapy

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

Group E: Turner Syndrome and galactosemia

Group F: Turner Syndrome with Y material

Trial outcomes

Primary outcomes

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.

Time frame