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Autologous Testicular Tissue Transplantation

Primary Purpose

Cancer, Sickle Cell Thalassemia, Hematologic Diseases

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Autologous testicular tissue transplantation of prepubertal frozen testicular tissue
Sponsored by
Universitair Ziekenhuis Brussel
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

The eligible patients opted as a prepubertal boy to enroll in the fertility preservation pro-gram and on the moment of cancer diagnosis or hematological disorder, their parents have agreed to cryopreserve testicular tissue for later autologous transplantation.

Inclusion Criteria:

  • At least 18 years old
  • Desire to become a parent at the moment of intake
  • Stable relationship with a female partner and minimal one year cohabiting
  • Age of female partner < 43 year
  • Azoospermia on 2 semen analyses
  • Normal standardised preliminary and preoperative bloodsampling results
  • Complete remission of the oncological or hematological disease
  • Approval of the treating oncologist or other specialist in case of non-oncological disease as reason for the testicular tissue preservation as a child
  • Risk for presence of malignant cells in testicular tissue is negligible (according to multidisciplinary assessment)
  • Presence of SSCs (positive MAGE staining) in one or two of the thawed fragments (If absence of SSCs in two of the thawed fragments, the case will be discussed multidisciplinary)
  • Written informed consent for the transplantation of cryopreserved testicular tissue and follow-up after the procedure and of children born eventually after this procedure

Exclusion criteria:

  • Risk for presence of malignant cells in the testicular tissue
  • Contra-indication for surgery
  • Contra-indication for pregnancy in the female partner
  • BMI > 32
  • Heavy smoking (≥10 cigarettes/day)
  • Instable psychological condition

Sites / Locations

  • UZ Brussel Centre for Reproductive MedicineRecruiting

Outcomes

Primary Outcome Measures

Restoration of spermatogenesis and fertility by performing an autologous testicular tissue transplantation. Primary endpoint is the presence of spermatozoa in the graft.
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs). If patient has a childwish on adult age and in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), we will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility. Grafting will be performed intra-testicular and intrascrotal for each patient. Grafts will be removed 12 months after grafting. Primary endpoint is the presence of spermatozoa in the grafted tissue.In the IVF laboratory mechanical mincing and enzymatic digestion will be performed on the tissue to find spermatozoa. If spermatozoa are present concentration and motility will be available.

Secondary Outcome Measures

Histological study to define the optimal transplantation site
The presence of sperm-generating stem cells, as well as their possible maturation to sperm cells will be evaluated through available and validated microscopic staining techniques applied to the testicular tissue. The maturity of other, non-sperm-generating testicular cells (Sertoli cells and Leydig cells) will also be evaluated. The results from tissue fragments transplanted to the testicle will be compared to the results from the tissue fragments transplanted to the scrotum. During the removal procedure of the transplanted fragments, a control biopsy (TESE) will be performed on the contra-lateral testicle (the one on which no transplantation was performed).
Imaging study
The investigators will study the possibility of analyzing the growth of the transplanted fragments and the development of sperm cell production in these fragments by using ultrasound and Doppler techniques in a non-invasive way. Ultrasound will be performed 3, 6, 9 and 12 months after grafting. These findings will be compared to the findings of the semen and blood analysis and the clinical examination.
Endocrinological (hormonal) study
The investigators plan a follow-up of the functionality of the transplanted tissue by performing blood analyses with LH (IU/L), FSH (IU/L), testosterone (ng/L), Inhibine B (ng/L) and Insulin-like factor 3 (INSL3, ng/ml). Blood analyses will be repeated 3, 6, 9 and 12 months after the transplantation procedure.
Biomarker Study
As an exploratory part of this study, the investigators will study the possibility to predict the presence of testicular spermatogenesis in a non-invasive way (by semen and/or urine samples). If different biomarkers could be identified specificaly for the different stages of spermatogenesis, the development of the transplanted biopsies could be monitored this way. For this study, a urine and semen sample will be needed 3, 6, 9 and 12 months after the transplantation procedure.
Complications
Each patient in the study will be followed-up during a period of 15 months after initial grafting or 3 months after graft-removal to report any complication(s) of the procedures.

Full Information

First Posted
February 17, 2022
Last Updated
June 7, 2022
Sponsor
Universitair Ziekenhuis Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT05414045
Brief Title
Autologous Testicular Tissue Transplantation
Official Title
Autologous Testicular Tissue Transplantation for Fertility Restoration
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2020 (Actual)
Primary Completion Date
July 29, 2030 (Anticipated)
Study Completion Date
October 29, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitair Ziekenhuis Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs) in case of imminent gonadotoxic treatment during childhood. In case of total azoospermia in adulthood and presence of a childwish, the investigators intend to perform the first in men autologous testicular tissue transplantation to restore fertility.
Detailed Description
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs). In 2002, the University hospital in Brussels (UZB) was the first hospital worldwide to offer testicular tissue cryobanking for fertility preservation in boys and ado-lescents. Since then, several other centers in Europe and USA have implemented similar fertility preservation programs. However, up till now, autologous transplantations of cryopreserved testicular tissue have not been performed yet. As soon as a patient returns to the Centre for Reproductive Medicine at UZB with the request to transplant the preserved testicular tissue, the investigators will first analyse semen and blood. If spermatozoa are found in their semen, men can immediately enroll in standard care for natural conception, intra-uterine insemination (IUI), in-vitro fertilization (IVF) or intra-cytoplasmic injection (ICSI). However, in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), the investigators intend to propose and eventually perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Sickle Cell Thalassemia, Hematologic Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
All eligible patients for the study will have the same treatment: autologous testicular tissue transplantation with testicular tissue containing spermatogonial stemcells frozen at pre-pubertal age. Transplantation will be performed subcutaneously in the scrotum and intra-testicular.
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Procedure
Intervention Name(s)
Autologous testicular tissue transplantation of prepubertal frozen testicular tissue
Intervention Description
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs). If patient has a childwish on adult age and in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), we will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.
Primary Outcome Measure Information:
Title
Restoration of spermatogenesis and fertility by performing an autologous testicular tissue transplantation. Primary endpoint is the presence of spermatozoa in the graft.
Description
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs). If patient has a childwish on adult age and in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), we will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility. Grafting will be performed intra-testicular and intrascrotal for each patient. Grafts will be removed 12 months after grafting. Primary endpoint is the presence of spermatozoa in the grafted tissue.In the IVF laboratory mechanical mincing and enzymatic digestion will be performed on the tissue to find spermatozoa. If spermatozoa are present concentration and motility will be available.
Time Frame
Graft-removal of intratesticular and intrascrotal grafts is planned 12 months after grafting.
Secondary Outcome Measure Information:
Title
Histological study to define the optimal transplantation site
Description
The presence of sperm-generating stem cells, as well as their possible maturation to sperm cells will be evaluated through available and validated microscopic staining techniques applied to the testicular tissue. The maturity of other, non-sperm-generating testicular cells (Sertoli cells and Leydig cells) will also be evaluated. The results from tissue fragments transplanted to the testicle will be compared to the results from the tissue fragments transplanted to the scrotum. During the removal procedure of the transplanted fragments, a control biopsy (TESE) will be performed on the contra-lateral testicle (the one on which no transplantation was performed).
Time Frame
Graft-removal of intratesticular grafts and intrascrotal grafts are planned 12 months after initial grafting. Histological study will be performed 12 months after initial grafting
Title
Imaging study
Description
The investigators will study the possibility of analyzing the growth of the transplanted fragments and the development of sperm cell production in these fragments by using ultrasound and Doppler techniques in a non-invasive way. Ultrasound will be performed 3, 6, 9 and 12 months after grafting. These findings will be compared to the findings of the semen and blood analysis and the clinical examination.
Time Frame
Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting.
Title
Endocrinological (hormonal) study
Description
The investigators plan a follow-up of the functionality of the transplanted tissue by performing blood analyses with LH (IU/L), FSH (IU/L), testosterone (ng/L), Inhibine B (ng/L) and Insulin-like factor 3 (INSL3, ng/ml). Blood analyses will be repeated 3, 6, 9 and 12 months after the transplantation procedure.
Time Frame
Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting.
Title
Biomarker Study
Description
As an exploratory part of this study, the investigators will study the possibility to predict the presence of testicular spermatogenesis in a non-invasive way (by semen and/or urine samples). If different biomarkers could be identified specificaly for the different stages of spermatogenesis, the development of the transplanted biopsies could be monitored this way. For this study, a urine and semen sample will be needed 3, 6, 9 and 12 months after the transplantation procedure.
Time Frame
Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting.
Title
Complications
Description
Each patient in the study will be followed-up during a period of 15 months after initial grafting or 3 months after graft-removal to report any complication(s) of the procedures.
Time Frame
Each patient in the study will be follow-up after screening during a period of 15 months post-grafting.

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Male infertile survivors of childhood cancer or a hematological disease who underwent prepubertal testicular tissue cryopreservation in case of gonadotoxic treatment.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
The eligible patients opted as a prepubertal boy to enroll in the fertility preservation pro-gram and on the moment of cancer diagnosis or hematological disorder, their parents have agreed to cryopreserve testicular tissue for later autologous transplantation. Inclusion Criteria: At least 18 years old Desire to become a parent at the moment of intake Stable relationship with a female partner and minimal one year cohabiting Age of female partner < 43 year Azoospermia on 2 semen analyses Normal standardised preliminary and preoperative bloodsampling results Complete remission of the oncological or hematological disease Approval of the treating oncologist or other specialist in case of non-oncological disease as reason for the testicular tissue preservation as a child Risk for presence of malignant cells in testicular tissue is negligible (according to multidisciplinary assessment) Presence of SSCs (positive MAGE staining) in one or two of the thawed fragments (If absence of SSCs in two of the thawed fragments, the case will be discussed multidisciplinary) Written informed consent for the transplantation of cryopreserved testicular tissue and follow-up after the procedure and of children born eventually after this procedure Exclusion criteria: Risk for presence of malignant cells in the testicular tissue Contra-indication for surgery Contra-indication for pregnancy in the female partner BMI > 32 Heavy smoking (≥10 cigarettes/day) Instable psychological condition
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Veerle Vloeberghs, MD
Phone
003224776699
Email
veerle.vloeberghs@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Herman Tournaye, MD PhD
Phone
003224776699
Email
herman.tournaye@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veerle Vloeberghs, MD
Organizational Affiliation
CRG UZ Brussel
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Brussel Centre for Reproductive Medicine
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Autologous Testicular Tissue Transplantation

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