About this trial
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells in case of imminent gonadotoxic treatment during childhood. In case of total azoospermia or absence of spermatozoa that can be used for intra-cytoplasmic injection (ICSI) in adulthood, the investigators intend to perform the first in men autologous testicular tissue transplantation to restore fertility.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
At least 18 years old
In case of female partner, age < 43 year
Absence of spermatozoa that can be used for ICSI on 2 semen analyses
Normal standardised preliminary and preoperative bloodsampling results
Disqualifiers
Risk for presence of malignant cells in the testicular tissue
Contra-indication for surgery
Contra-indication for pregnancy in the female partner
BMI > 32
Trial design
Single group
Treatments tested in this trial
Autologous testicular tissue transplantation of prepubertal frozen testicular tissue
Procedure/SurgeryFreezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells. If no spermatozoa suitable for ICSI are detected in the ejaculate, the investigators will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.
Treatment groups
Trial outcomes
Primary outcomes
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. If the patient has no spermatozoa suitable for ICSI in the ejaculate in adulthood, the investigators 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 outcomes
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.
Sponsors and contacts
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Universitair Ziekenhuis Brussel
Lead sponsor
Vrije Universiteit Brussel
Collaborator