Testicular Tissue Cryopreservation in the Setting of Gender-Affirming Therapy

The goal of this study is to learn about fertility preservation in the gender-diverse community. The main objectives it aims to understand are to:

1. Optimize techniques for processing and cryopreserving testicular tissue.
2. Determine presence and number of germ cells (sperm precursors) in the patients' testicular tissue.
3. Develop next generation cell- and tissue-based therapies for preserving fertility and treating infertility.

Study Overview

• Status: Recruiting
• Conditions: Gender Dysphoria; Transgender
• Intervention / Treatment: Diagnostic test: Infectious Disease Testing; Procedure: Gonadal Tissue Removal

Detailed Description

Fertility preservation is an important aspect of care for all patients who may have their fertility compromised secondary to disease, medical treatments, age or other circumstances, including treatments for gender dysphoria. An increasing number of gender diverse patients are presenting to fertility clinics for fertility preservation. Studies indicate that parenthood is important for this patient population. Therefore, both the Endocrine Society and the World Professional Association for Transgender Health (WPATH) recommend that fertility preservation be discussed with all patients prior to initiation of medical treatments for gender dysphoria.

For gender diverse patients, medical treatment is primarily comprised of estradiol, which is often preceded by GnRH agonists (such as leuprolide acetate, histrelin) to reduce endogenous testosterone production. There are theoretical concerns about the effects of long-standing hormonal treatment on the gonads and future fertility potential. Regardless of the timing of initiation of hormone suppression and/or estradiol therapy, fertility preservation counseling is an essential aspect of their care. Sperm preservation does require the individual to undergo their natal puberty, and for many transgender patients, this is undesirable and even contra-indicated from mental health standpoint, as the suicide rate for transgender youth is 10-times the national average. Testicular tissue cryopreservation is an alternative option for transgender patients who desire pubertal blockade and estradiol but have not yet initiated sperm production (spermarche) to preserve their fertility. Spermarche typically occurs at sexual maturity rating (SMR) 4 and pubertal blockade is offered as early as SMR 2.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Rachel Neelley, BA; Phone Number: 1 4126417475; Email: fertilitypreservation@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Magee-Womens Hospital
      • Contact: Rachel Neelley, BA; Phone Number: 1 412-641-7475; Email: fertilitypreservation@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients who will undergo gender-affirming treatments and for whom standard of care fertility preservation procedures are not available.

Description

Inclusion Criteria:

Category 1 participants must have all criteria listed below:

• Patient with testes over the age of 9
• Diagnosed with gender dysphoria; currently on or imminently planning to start gender affirming treatment (hormone blockers or gender-affirming hormones)
• Have a clinical referral for fertility preservation from their primary care physician
• Unwilling to undergo natal puberty or, for patients who have gone through puberty, unwilling to discontinue hormone suppression and/or hormone replacement therapy.

Category 2 participants only fall into this category if they are undergoing gender-affirming surgery. They must have all criteria listed below:

• Patient is 18+ years old
• Diagnosed with gender dysphoria
• Unwilling to undergo natal puberty, or for patients who have gone through puberty, be unwilling to discontinue hormone suppression and/or sex steroid (estrogen) therapy.
• Will be undergoing gender affirming surgery that involves removal of the testes.

Exclusion Criteria:

• Diagnosed with psychological, psychiatric, or other conditions which prevent giving fully informed consent.
• Diagnosed with an underlying medical condition that significantly increases their risk of complications from anesthesia and surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cryopreservation; Participants will have gonadal tissue removed and cryopreserved for future fertility applications.	Diagnostic test: Infectious Disease Testing; Participants will undergo infectious disease testing.; Procedure: Gonadal Tissue Removal; Removal of gonadal tissue will be done through a surgical procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimization of testicular tissue/cell cryopreservation techniques	Testicular tissue will be used to isolate a suspension of testicular cells using a series of enzymatic digestions, washes, and filtrations. Testicular cells donated to the research pool will be frozen using varying cryopreservation methods and thawed to determine the efficacy of the freeze/thaw techniques. The concentration and number of recovered spermatogonial stem cells in the thawed cells will be determined using a human-to-nude mouse xenotransplantation assay. Recovery of spermatogonial stem cells will be compared to the concentration and number prior to cryopreservation using the same assay. Data gathered from this research will assist in identifying and overcoming some of the challenges to successful freezing and thawing of cells for future use by the patient.	[10 years]
To determine presence and number of germ cells (sperm precursors) in the patients' testicular tissue	The number of stem cells in the developing testis in the humans is currently not established. Therefore, a small piece of testicular tissue from each patient (from the research portion) will be fixed in 4% of paraformaldehyde (PFA) and stained for known germ cell markers in order to count the number of stem cells in the patient tissue.	[10 years]

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Kyle Orwig, PhD, University of Pittsburgh/ University of Pittsburgh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Infertility; Fertility; Fertility Preservation; Gender Diverse; Gender Affirming; Non-Binary
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Gender Dysphoria
• Other Study ID Numbers: STUDY19070264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will publish individual participant data. The investigators will also report each individual participant's data back to them. Participants will be identified with unique ID numbers. No identifiable information will be shared.
• IPD Sharing Time Frame: We will share IPD with the patients (and only the patient) within one year of enrollment. We share study protocol and ICF with collaborating sites upon request. De-identified IDP is shared with collaborating sites annually.
• IPD Sharing Access Criteria: De-identified research data will be shared with collaborators via e-mail, and with the broader scientific community via publication and presentations at national/international meetings.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No