Gonadal Dysgenesis Tissue Cryopreservation for Fertility Preservation

Overview

The "Gonadal Dysgenesis Tissue Cryopreservation for Fertility Preservation" study is open to a subset of patients with disorders of sex development (DSD) which is associated with the risk of malignancy and a high risk of infertility or sterility. For these patients, experimental gonadal tissue cryopreservation is the only fertility preservation option available. The overall objective of this study is to determine the safety and efficacy of gonadal tissue cryopreservation as a method of preserving fertility and/or restoring hormonal function in patients with gonadal dysgenesis who are at risk of decreased fertility potential or malignancy.

Detailed description

Unlike the oncology population, in which patients have inherently normal fertility potential and reproductive function, individuals with DSD may have infertility caused by 1) abnormal gonadal development, 2) gonadectomy performed for risk of malignancy, 3) abnormal hormone production or, 4) discordance, or difference, between gonadal type and gender identity. Fertility potential differs according to the specific DSD diagnosis and can also be influenced by age, genetic mosaicism, and/or risk of developing a gonadal malignancy.

Abnormal gonadal development can result in gonadal failure, either in infancy or progressively, such that individuals may not undergo spontaneous puberty, menarche or spermarche. Progressive germ cell loss may occur throughout childhood. In addition, abnormal gonadal development in certain cellular environments leads to an increased risk of germ cell cancer. Traditionally, it was recommended to perform gonadectomy at the time of diagnosis in all DSD conditions with a risk of gonadal tumor formation. The estimated tumor risk ranges from 2% in complete androgen insensitivity syndrome to 40% in partial androgen insensitivity syndrome. Advances in stratification of tumor risk have led to a more diagnosis-specific assessment of risk, but tumor risk remains a major concern.

Thus, the investigators are conducting a pilot study to assess the safety and efficacy of gonadal tissue cryopreservation as a method of preserving fertility and/or restoring hormonal function in patients with gonadal dysgenesis who are at risk of decreased fertility potential or malignancy.

Interventions

• Other Cryopreservation of gonadal tissue
  Patients at risk for primary gonadal tumors will undergo unilateral or bilateral gonadectomy for clinical purposes as a standard of care, and a portion of the surgically removed tissue will be cryopreserved for fertility preservation. The pathologist will assess the tissue using sterile technique and every other section will undergo histologic analysis, including evaluation for the presence of tumor or viable germ cell elements. The sections of the tissue for fertility preservation will be refri

Primary outcome measures

• Efficacy, as Assessed via the Proportion of total samples containing viable gonadal tissue and/or the presence of germ cells, and the Proportion of total samples that were successfully cryopreserved for the patient's future use. [Time frame: Up to 48 hours after obtaining gonadal tissue samples.]
• Safety, as Assessed via the Proportion of adverse events [Time frame: within 72 hours of gonadal tissue removal]
• Acceptability as a fertility preservation method, as Assessed via the survey responses by eligible patients and/or their guardians. [Time frame: Through study completion, up to ten years.]
• Level of demand [Time frame: Through study completion, up to ten years.]

Secondary outcome measures (2)

• Create a recruitment database of patients/caregivers that consent to future contact to consider participating in other research studies pertaining to fertility preservation. [Time frame: Through study completion, up to ten years.]
• Determine if there are disparities in the type of patients consenting to future contact for research studies pertaining to fertility preservation [Time frame: Through study completion, up to ten years.]

Eligibility criteria

Inclusion criteria

• < 30 years of age
• Individuals diagnosed with a disorder of sex development who have any risk for malignancy in their gonadal tissue and will have their gonads removed for a clinical indication
• Individuals diagnosed with a disorder of sex development who are at risk of primary ovarian insufficiency (POI) due to an underlying genetic condition

Exclusion criteria

• Pregnancy
• Patients likely to retain inherent fertility and reproductive function
• Patients deemed high risk for perioperative complications
• Patients 7-17 years of age unable to provide assent (i.e. significant psychiatric problems/cognitive delay)
• Patients 18 and older unable to provide consent (i.e. significant psychiatric problems/cognitive delay)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• University of Colorado — Aurora

Identifiers

NCT: NCT06518746 · 21-3159

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗