Gonadal development and function after high-risk gonadotoxic treatment and immature testicular tissue banking

Study question What is the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function of pre- and pubertal boys? Summary answer There is a risk for impaired reproductive hormone levels after high-risk gonadotoxic treatment protocols, especially after conditioning therapy before hematopoietic stem cell transplantation. What is known already Experimental fertility preservation programs have been started to safeguard the future fertility of pre- and pubertal boys requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies on their gonadal development and function are rather limited. Study design, size, duration A two-center follow-up study, conducted between 2002 and 2020, evaluated the gonadal development and function of pre- and pubertal boys who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of a high-risk gonadotoxic treatment and the testicular biopsy procedure. Participants/materials, setting, methods A cohort of 60 pre- and pubertal boys without ongoing spermatogenesis and requiring HR-C/R or CT-HSCT were included. Exclusion criteria were testicular cancer diagnosis and hormonal substitution treatment. Testicular growth measured with a Prader orchidometer and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and inhibin B (INHB) were analyzed after treatment completion and compared between HR-C/R and CT-HSCT treatment protocols as well as between boys accepting TTB and those refusing TTB. Main results and the role of chance Of the 60 pre- and pubertal boys included, 26 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted by 39 boys and refused by 21 boys. Most boys were prepubertal at diagnosis (87%), at treatment completion (78%) and at TTB (79%). After 5.0 (1.0-11.0) years post-treatment, most patients had normal testicular volumes (86%) and normal LH (81%), FSH (81%), testosterone (70%) and INHB (65%) serum levels. Testicular growth (P = 0.3773), LH (P = 0.4844), FSH (P = 0.1613) and INHB (P = 0.2553) were not significantly different between the treatment groups, but significantly more abnormal testosterone serum levels (P = 0.0138) were recorded after CT-HSCT (43%) compared to HR-C/R (10%). TTB had no effect on testicular growth (P > 0.9999), LH (P = 0.7186), FSH (P > 0.9999) and INHB (P = 0.7074). A significant difference for testosterone was observed between the TTB groups (P = 0.0210), but no significant difference for testosterone or the other hormones was observed when comparing the effect of the biopsy procedure within each treatment group separately. The Spearman’s correlation test reveals a significant positive correlation between patients treated by CT-HSCT and patients having chosen for TTB (P < 0.001). In boys who underwent a hemi-orchiectomy or small biopsy, the volumes of the biopsied and contralateral non-biopsied testes were not significantly different (P > 0.9999). Limitations, reasons for caution This clinical follow-up study included a low patient number and the follow-up period was rather limited. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings. Wider implications of the findings A more accurate understanding of the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function will allow better counseling of patients interested in fertility preservation and optimize selection of patients eligible for fertility preservation. Trial registration number not applicable Issue Section: Male and female fertility preservation PDF