{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:09:06Z","timestamp":1792022946378,"version":"4.4.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Salus Sanguinis Foundation and the Belgian Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n What is the long-term reproductive health outcome of patients who have undergone testicular sampling for fertility preservation (FP) before and during the pubertal transition period?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n In long-term follow-up after testicular sampling for FP, hormonal data showed that 33% of patients had primary seminiferous tubule insufficiency (high FSH) while semen analyses showed 52% of patients having a severe reduction in total sperm counts or complete absence of ejaculated sperm.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n During childhood and adolescence, both treatments for cancer and benign haematological diseases that require a bone marrow transplantation, can be detrimental to spermatogenesis by depleting the spermatogonial stem cell population. A testicular biopsy prior to chemotherapy or radiotherapy, even though still an experimental procedure, is now recommended for FP by European and USA oncofertility societies if performed within an institutional research setting. While short-term follow-up studies showed little to no post-operative complications and a normal testicular development after 1 year, data regarding the long-term follow-up of boys who have undergone this procedure are still lacking.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n This is a longitudinal retrospective cohort study that reports on the long-term follow-up of pre- and peri-pubertal boys who have undergone a testicular biopsy for FP between May 2005 and May 2020. All the patients included in this study were referred to our programme by haematologists-oncologists who are part of a regional multi-centric collaborative care pathway.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n Of the 151 boys referred to our FP programme, 139 parents\/legal guardians accepted that their child undergo a testicular biopsy. Patient characteristics (i.e. age at biopsy, urogenital history, pubertal status at diagnosis), indications (disease type and dosage of gonadotoxic treatments), operative and post-operative data (biopsy volume, surgical complications), anatomopathological analyses (presence\/absence of spermatogonia, Johnsen score) and reproductive data (semen analyses, FSH, LH, testosterone levels) were collected from the institutions\u2019 FP database and medical records or from the \u2018Brussels Health Network\u2019. Cumulative alkylating agent treatment was quantified using the cyclophosphamide equivalent dose (CED). Patients who were 14\u2009years or older at the time of the follow-up and in whom the testicular tissue was shown to contain spermatogonia were included in the reproductive outcome analysis. Comparison of the sperm count findings (absence\/presence of spermatozoa) and FSH levels (high (\u226510\u2009IU\/l)\/normal) between patients who were either pre- (Tanner 1) or peri-pubertal (Tanner &gt;1) at the time of the biopsy was done using the Mann\u2013Whitney U or Fisher\u2019s tests. A multiple logistic regression was used to study the relationship between the hormone reproductive outcome (high versus normal FSH), as a proxy marker for fertility, and both the pubertal status (Tanner 1 versus Tanner &gt;1) and Johnsen score at the time of the biopsy, while adjusting for CED.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n A testicular biopsy was performed in 139 patients either before (129\/139) or after (10\/139) the start of a gonadotoxic treatment. Post-operative complications occurred in 2.1% (3\/139). At the time of the procedure, 88% (122\/139) of patients were pre-pubertal and 12% (17\/139) were peri-pubertal. The presence of spermatogonia was documented in 92% (128\/139) of cases. Follow-up data were available for 114 patients after excluding 23 deceased and two patients lost to follow-up. A paediatric endocrinologist\u2019s follow-up including clinical examination and data on reproductive hormones was available for 57 patients (age \u226514) and 19 (33%) of these were found to have high FSH levels (20\u2009\u00b1\u20098.8\u2009IU\/l). There were 37 patients who had returned to the reproductive specialist\u2019s consultation for post-treatment fertility counselling and results on semen analysis were available in 27 of these cases; 14\/27 (52%) had severely impaired semen parameters including 8 who were azoospermic. Among patients who received an alkylating agent-based treatment (n\u2009=\u200942), a peri-pubertal status (Tanner &gt;1) at the time of diagnosis\/biopsy was found to be associated with a higher risk of having primary testicular failure (defined by an FSH\u2009\u2265\u200910\u2009IU\/l) after treatment completion with an OR of 6.4 (95% CI 1.22\u201333.9; P\u2009=\u20090.03). Of all the patients, 2.6% had already fulfilled their wish to build a family or were actively seeking parenthood.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n Although this is the largest cohort with follow-up data providing proxy markers of the reproductive potential of boys in whom a testicular biopsy for FP was performed before puberty or during the pubertal transition period, the amount of data provided is limited, and originating from a single programme. Further data collection to confirm the observations in other settings is therefore awaited.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n Testicular sampling for FP should be offered to boys at risk of losing their fertility (and is recommended for those at high risk) as part of ethically approved research programmes. Long-term follow-up data on increasing numbers of boys who have undergone an FP procedure will help improve patient care in the future as patient-specific factors (e.g. urogenital history, age at gonadotoxic therapy) appear to influence their reproductive potential after gonadotoxic therapies.<\/jats:p>\n <\/jats:sec>\n \n STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n FNRS-T\u00e9l\u00e9vie, the Salus Sanguinis Foundation and the Belgian Foundation against Cancer supported the studies required to launch the FP programme. The authors declare that they have no conflict of interest.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/deaa281","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T19:15:54Z","timestamp":1602011754000},"source":"Crossref","is-referenced-by-count":17,"title":["Long-term follow-up of boys who have undergone a testicular biopsy for fertility preservation"],"prefix":"10.1093","author":[{"given":"M","family":"Kanbar","sequence":"first","affiliation":[{"name":"Andrology Lab, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Brussels 1200, Belgium"},{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"de Michele","sequence":"additional","affiliation":[{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M G","family":"Giudice","sequence":"additional","affiliation":[{"name":"Andrology Lab, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Brussels 1200, Belgium"},{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Desmet","sequence":"additional","affiliation":[{"name":"Louvain Institute of Data Analysis and Modeling in economics and statistics (LIDAM), Louvain-la-Neuve 1348, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Poels","sequence":"additional","affiliation":[{"name":"Andrology Lab, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Brussels 1200, Belgium"},{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Wyns","sequence":"additional","affiliation":[{"name":"Andrology Lab, Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Brussels 1200, Belgium"},{"name":"Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2020120111465170900_deaa281-B1","doi-asserted-by":"crossref","first-page":"R209","DOI":"10.1530\/REP-18-0221","article-title":"How does chemotherapy treatment damage the prepubertal testis?","volume":"156","author":"Allen","year":"2018","journal-title":"Reproduction"},{"key":"2020120111465170900_deaa281-B2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biomaterials.2017.03.025","article-title":"Testicular organoid generation by a novel in vitro three-layer gradient system","volume":"130","author":"Alves-Lopes","year":"2017","journal-title":"Biomaterials"},{"key":"2020120111465170900_deaa281-B3","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S2213-8587(15)00039-X","article-title":"Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults","volume":"3","author":"Anderson","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2020120111465170900_deaa281-B4","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S1470-2045(18)30498-4","article-title":"Increasing incidence of cancer in children and competing risks","volume":"19","author":"Autier","year":"2018","journal-title":"Lancet Oncol"},{"key":"2020120111465170900_deaa281-B5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10815-012-9909-5","article-title":"Evaluation of ovarian and testicular tissue cryopreservation in children undergoing gonadotoxic therapies","volume":"30","author":"Babayev","year":"2013","journal-title":"J Assist Reprod Genet"},{"key":"2020120111465170900_deaa281-B6","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1093\/humrep\/15.6.1416","article-title":"Testicular tissue cryopreservation in boys. 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