Immature testicular tissue banking for fertility preservation in (pre) pubertal boys: patient enrolment and follow-up

Onderzoeksoutput: PhD Thesis

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Endocrine and gonadal dysfunction causing transient or permanent infertility are recognised side effects of gonadotoxic treatment protocols and certain genetic conditions. The patient’s future fertility, especially the ability to father his own children, is important for his quality of life. Therefore, a considerable research effort was dedicated to the development of fertility preservation methods for adult men and later also for prepubertal boys at significant risk for later fertility problems. Adult men have the option to cryopreserve mature spermatozoa before initiation of gonadotoxic treatment, unlike prepubertal boys who do not yet produce mature spermatozoa. Spermatogonial stem cells are present in the testes of prepubertal boys and can be collected and cryopreserved by harvesting some testicular tissue. At present, this experimental method of immature testicular tissue banking represents the only fertility preservation option for prepubertal boys. Its acceptance is reflected by an ever-increasing number of fertility centres across the world offering immature testicular tissue banking to prepubertal boys facing later infertility. Despite its worldwide acceptance, the patients eligible for immature testicular tissue banking remain vague as the exact impact of gonadotoxic treatment protocols on the patient’s gonadal development and reproductive capacity are still under investigation. This is especially true for boys who receive such treatments before or during puberty, a period marked by testicular maturation regulated by changes in reproductive hormone levels. The surgical removal of immature testicular tissue is performed without exactly knowing the potential adverse effects on pubertal development and later fertility. The general aim of this PhD thesis was to investigate the impact of the testicular biopsy procedure and the long-term impact of gonadotoxic treatment protocols on the patient’s gonadal development and reproductive health.
The first part of this PhD thesis describes the clinical fertility preservation programmes launched at the UZ Brussel and in other European and North American centres/networks for prepubertal boys at high risk of treatment- or condition-related infertility. A proper and efficient management of fertility preservation programmes relies on a multidisciplinary and closely cooperating team of physicians, nurses, and psychologists with expertise in oncology, genetics and reproductive medicine. The acceptance of immature testicular tissue banking is reflected by the constantly increasing number of prepubertal boys undergoing a testicular biopsy for fertility preservation: worldwide over 1033 boys (age range 3 months to 18 years) in 2019.
The second part of this PhD thesis investigates the impact of a testicular biopsy procedure and high-risk gonadotoxic treatment protocols on the gonadal development and function of young patients diagnosed with malignant or non-malignant disorders as well as early-diagnosed Klinefelter patients. Based on the clinical data retrospectively collected over a long period after immature testicular tissue banking and treatment completion, we conclude that a testicular biopsy procedure does not have an additional negative impact on testicular growth and reproductive hormone levels throughout puberty. In young boys treated with gonadotoxic treatment protocols, however, the treatment constitutes a substantial risk for small postpubertal testicular volumes and impaired reproductive hormone levels. Especially in patients treated with myeloablative conditioning therapies prior to haematopoietic stem cell transplantation. Follow-up of early-diagnosed Klinefelter patients at the UZ Brussel revealed behavioural, cognitive and/or psychological problems of which the psychological problems influence the parents’ decision towards fertility preservation for their son. However, before the safety of a testicular biopsy procedure as part of immature testicular tissue banking can be concluded, its impact on the later reproductive potential needs to be studied.
Originele taal-2English
KwalificatieDoctor in Medical Sciences
Toekennende instantie
  • Vrije Universiteit Brussel
Begeleider(s)/adviseur
  • Goossens, Ellen, Promotor
  • Gies, Inge, Co-Promotor
Datum van toekenning26 jan 2023
Plaats van publicatieBrussel
Uitgever
Gedrukte ISBN's9789464443493
StatusPublished - 2023

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