Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients

Abstract

Study question: What is the long-term impact of presumed gonadotoxic treatment during childhood on the patient's testicular function at adulthood?

Summary answer: Although most patients showed low testicular volumes and some degree of reproductive hormone disruption 12.3 (2.3-21.0) years after gonadotoxic childhood therapy, active spermatogenesis was demonstrated in the semen sample of 8 out of the 12 patients.

What is known already: In recent decades, experimental testicular tissue banking programmes have been set up to safeguard the future fertility of young boys requiring chemo- and/or radiotherapy with significant gonadotoxicity. Although the risk of azoospermia following such therapies is estimated to be high, only limited long-term data are available on the reproductive potential at adulthood.

Study design size duration: This single-centre prospective cohort study was conducted between September 2020 and February 2023 and involved 12 adult patients.

Participants/materials setting methods: This study was carried out in a tertiary care centre and included 12 young adults (18.1-28.3 years old) who had been offered testicular tissue banking prior to gonadotoxic treatment during childhood. All patients had a consultation and physical examination with a fertility specialist, a scrotal ultrasound to measure the testicular volumes and evaluate the testicular parenchyma, a blood test for assessment of reproductive hormones, and a semen analysis.

Main results and the role of chance: Testicular tissue was banked prior to the gonadotoxic treatment for 10 out of the 12 included patients. Testicular volumes were low for 9 patients, and 10 patients showed some degree of reproductive hormone disruption. Remarkably, ongoing spermatogenesis was demonstrated in 8 patients at a median 12.3 (range 2.3-21.0) years post-treatment.

Limitations reasons for caution: This study had a limited sample size, making additional research with a larger study population necessary to verify these preliminary findings.

Wider implications of the findings: These findings highlight the need for multicentric research with a larger study population to establish universal inclusion criteria for immature testicular tissue banking.

Study funding/competing interests: This study was conducted with financial support from the Research Programme of the Research Foundation-Flanders (G010918N), Kom Op Tegen Kanker, and Scientific Fund Willy Gepts (WFWG19-03). The authors declare no competing interests.

Trial registration number: NCT04202094; https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 This study was registered on 6 December 2019, and the first patient was enrolled on 8 September 2020.

Keywords: cancer; fertility preservation; gonadotoxic treatment; male infertility; testicular tissue banking.

Figure 1.

Schematic overview of the study design to investigate the testicular function after gonadotoxic childhood treatment. T: testosterone; INHB: inhibin B.