Clinical trial NCT05414045: Autologous Testicular Tissue Transplantation
Official title: Autologous Testicular Tissue Transplantation for Fertility Restoration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cancer
Sickle Cell Thalassemia
Hematologic Diseases
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: Vrije Universiteit Brussel
First posted: 2022-06-10
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All eligible patients for the study will have the same treatment: autologous testicular tissue transplantation with testicular tissue containing spermatogonial stem cells frozen at pre-pubertal age. Transplantation will be performed subcutaneously in the scrotum and intra-testicular.
Primary purpose: TREATMENT

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 the investigators intend to propose and eventually perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.

Eligibility criteria: The eligible patients opted as a prepubertal boy to enroll in the fertility preservation program 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

Primary outcomes:
measure: Restoration of spermatogenesis and fertility by performing an autologous testicular tissue transplantation. Primary endpoint is the presence of spermatozoa in the graft.
timeFrame: Graft-removal of intratesticular and intrascrotal grafts is planned 12 months after grafting.
Secondary outcomes:
measure: Histological study to define the optimal transplantation site
timeFrame: 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
measure: Imaging study
timeFrame: 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.
measure: Endocrinological (hormonal) study
timeFrame: 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.
measure: Biomarker Study
timeFrame: 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.
measure: Complications
timeFrame: Each patient in the study will be follow-up after screening during a period of 15 months post-grafting.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussel Centre for Reproductive Medicine
Study officials:
affiliation: CRG UZ Brussel
name: Veerle Vloeberghs, MD
role: PRINCIPAL_INVESTIGATOR
References: