Fertility in Young Adults Who Did (Not) Store Testicular Tissue Before a Treatment Leading to Fertility Problems

Follow-up of Fertility in Young Adults Who Did or Did Not Store Testicular Tissue Before Gonadotoxic Treatment for Fertility Preservation

The goal of this prospective comparative interventional cohort study is to assess the fertility status of young adult men (≥18 years) who received gonadotoxic treatment during childhood for the treatment of cancer or hematological disorders. These treatment protocols are highly gonadotoxic (i.e. they may cause later fertility problems) and therefore these patients have been proposed to store some testicular tissue during childhood as an option to preserve their fertility.

The main questions this study aims to answer are (1) the impact of the received gonadotoxic treatment on the later fertility status and (2) the additional impact of a testicular biopsy procedure (performed at a young age to harvest testicular tissue for storage) on the future fertility.

Participants will be asked to undergo a physical examination by a fertility specialist, to undergo a scrotal ultrasound, to give a blood sample, and to provide a semen sample.

Researchers will compare the patients fertility status between the different received gonadotoxic treatment protocols, between patients who underwent a testicular biopsy procedure at a young age and those who did not, and compare the patients fertility status with the reproductive health of spontaneously conceived young adults.

Study Overview

• Status: Enrolling by invitation
• Conditions: Childhood Cancer; Hematological Disorders
• Intervention / Treatment: Diagnostic test: Physical examination; Diagnostic test: Scrotum ultrasound; Diagnostic test: Semen analysis; Diagnostic test: Blood sample

Detailed Description

See the subsequent protocol sections.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Universitair Ziekenhuis Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• young adult men (≥18 years)
• diagnosis of cancer or hematological disorder during childhood (<18 years)
• high-risk gonadotoxic treatment received during childhood
• at least one year after the last received genotoxic treatment
• did/did not undergo a testicular biopsy procedure at a young age for fertility preservation

Exclusion criteria

- prepubertal patients and adolescents (<18 years)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Spontaneously conceived young adults whose data on reproductive health have already been published (Belva F et al., 2016/2017/2019).
Experimental: Biopsy group; Young adult men (≥18 years) cured of childhood cancer or hematological disorders for which they received high-risk gonadotoxic treatment during childhood and who have chosen to undergo a testicular biopsy procedure at a young age as a fertility preservation strategy.	Diagnostic test: Physical examination; A physical examination to measure the patients' weight, height, body mass index, blood pressure and testicular volume using a Prader orchidometer and to determine the patients' Tanner stage (secondary sexual development).; Diagnostic test: Scrotum ultrasound; A scrotum ultrasound to measure the patients' testicular volume and to investigate potential abnormalities in the testicular parenchyma.; Diagnostic test: Semen analysis; A semen analysis to evaluate ejaculate volume, sperm concentration, sperm motility, and sperm morphology. If sperm is found in the semen sample, an anti-sperm antibody test and a sperm DNA fragmentation test will be performed. Upon approval by the patient himself, the surplus of the semen sample will be retained for 5 years for subsequent research purposes limited to the context of the present study.; Diagnostic test: Blood sample; A morning blood sample to evaluate the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), inhibin B (INHB) and insulin-like peptide 3 (INSL3). Upon approval by the patient himself, a spare blood sample will be collected and retained for 5 years for subsequent research purposes limited to the context of the present study.
Experimental: No biopsy group; Young adult men (≥18 years) cured of childhood cancer or hematological disorders for which they received high-risk gonadotoxic treatment during childhood and who have refused to undergo a testicular biopsy procedure at a young age as a fertility preservation strategy.	Diagnostic test: Physical examination; A physical examination to measure the patients' weight, height, body mass index, blood pressure and testicular volume using a Prader orchidometer and to determine the patients' Tanner stage (secondary sexual development).; Diagnostic test: Scrotum ultrasound; A scrotum ultrasound to measure the patients' testicular volume and to investigate potential abnormalities in the testicular parenchyma.; Diagnostic test: Semen analysis; A semen analysis to evaluate ejaculate volume, sperm concentration, sperm motility, and sperm morphology. If sperm is found in the semen sample, an anti-sperm antibody test and a sperm DNA fragmentation test will be performed. Upon approval by the patient himself, the surplus of the semen sample will be retained for 5 years for subsequent research purposes limited to the context of the present study.; Diagnostic test: Blood sample; A morning blood sample to evaluate the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), inhibin B (INHB) and insulin-like peptide 3 (INSL3). Upon approval by the patient himself, a spare blood sample will be collected and retained for 5 years for subsequent research purposes limited to the context of the present study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of childhood gonadotoxic treatment on fertility status	The patients' fertility status (physical examination, scrotum ultrasound, blood sample, semen analysis) will be evaluated once a year after cessation of the gonadotoxic treatment. Only in case of infertility (azoospermia) or subfertility (oligo-, astheno- or teratozoospermia), the different interventions will be repeated one year later as the recovery of spermatogenesis with return of sperm production may occur several years after gonadotoxic treatment.	at baseline and in 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of testicular biopsy procedure (performed at a young age) on fertility status	The patients' fertility status (physical examination, scrotum ultrasound, blood sample, semen analysis) will be evaluated once a year after cessation of the gonadotoxic treatment. Only in case of infertility (azoospermia) or subfertility (oligo-, astheno- or teratozoospermia), the different interventions will be repeated one year later as the recovery of spermatogenesis with return of sperm production may occur several years after gonadotoxic treatment.	at baseline and in 1 year

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Collaborators: Vrije Universiteit Brussel
• Investigators: Principal Investigator: Ellen Goossens, Prof. Dr., Vrije Universiteit Brussel

Publications and helpful links

General Publications

• Belva F, Bonduelle M, Roelants M, Michielsen D, Van Steirteghem A, Verheyen G, Tournaye H. Semen quality of young adult ICSI offspring: the first results. Hum Reprod. 2016 Dec;31(12):2811-2820. doi: 10.1093/humrep/dew245. Epub 2016 Oct 5.
• Belva F, Roelants M, De Schepper J, Van Steirteghem A, Tournaye H, Bonduelle M. Reproductive hormones of ICSI-conceived young adult men: the first results. Hum Reprod. 2017 Feb;32(2):439-446. doi: 10.1093/humrep/dew324. Epub 2016 Dec 21.
• Belva F, Bonduelle M, Tournaye H. Endocrine and reproductive profile of boys and young adults conceived after ICSI. Curr Opin Obstet Gynecol. 2019 Jun;31(3):163-169. doi: 10.1097/GCO.0000000000000538.
• Delgouffe E, Braye A, Vloeberghs V, Mateizel I, Ernst C, Ferster A, Devalck C, Tournaye H, Gies I, Goossens E. Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients. Hum Reprod Open. 2023 Jul 31;2023(3):hoad029. doi: 10.1093/hropen/hoad029. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hormones; Semen analysis; Male fertility preservation; Testicular tissue biopsy; Male fertility status; Tanner stage; Testicular volume
• Additional Relevant MeSH Terms: Hemic and Lymphatic Diseases; Neoplasms; Hematologic Diseases; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection; Physical Examination; Semen Analysis
• Other Study ID Numbers: 2019-342

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No