Autologous Testicular Tissue Transplantation

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-50
SponsorUniversitair Ziekenhuis Brussel

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 volunteers

Qualifiers

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

Design model

Single group

Treatments tested in this trial

  • Autologous testicular tissue transplantation of prepubertal frozen testicular tissue

    Procedure/Surgery

    Freezing 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

5 Participants
are divided into 1 treatment group
Group A: PatientsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
Graft-removal of intratesticular and intrascrotal grafts is planned 12 months after grafting.

Secondary outcomes

1

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).

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
2

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.

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.
3

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.

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.
4

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.

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.

Other outcomes

Sponsors and contacts

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Universitair Ziekenhuis Brussel

Lead sponsor

Vrije Universiteit Brussel

Collaborator