Abstract

Abstract Study question To examine the influence of patient- and cancer treatment-related factors on the quality of semen and testicular tissue samples collected 2004-2019 in our centre. Summary answer Semen quality was reduced before cancer treatment in patients with a testicular or haematological malignancy and following any gonadotoxic-risk treatment when compared to no-risk treatment. What is known already Young men with cancer are at increased risk of fertility impairment. Therefore, cryopreservation of semen or testicular tissue is recommended. Usually, these steps are taken before cancer treatment. However, in some cases it may be necessary to undergo fertility protection following gonadotoxic treatment. The cancer diagnosis itself may have a negative impact on semen quality. Fertility impairment may occur especially following treatment with alkylating agents, radiotherapy to the pelvis/testes and high dose treatment as used in stem cell transplantation regimen. Risk groups have been defined according to the gonadotoxicity of cancer treatment in previous guidelines. Study design, size, duration In our centre, patients have been cryopreserving semen and/or testicular tissue samples for more than 15 years now. We conducted a retrospective cohort study between 01/2020 and 09/2021 in the subgroup of 506 cancer patients that had collected samples in our department between 03/2004 and 05/2019 and for whom cancer treatment data was available. In total, we included information on 601 samples (semen and testicular tissue) from these patients. Participants/materials, setting, methods Cancer treatment data and results from semen/testicular tissue analyses were collected from medical records. Cancer diagnoses were classified as brain, testicular or solid tumors in other locations or haematological malignancies. Samples were categorized as collected before or after the start of a gonadotoxic treatment (high/medium/low/no, defined according to existing guidelines). Descriptive analyses and multiple linear and logistic regression were conducted to determine influencing factors on the quality of cryopreservation in adolescent and adult cancer patients. Main results and the role of chance Over the period of 15 years, we observed an overall increase in sperm concentration and progressive motility in adolescent cancer samples, whereas concentrations remained stable during this period in adult samples. However, before cancer treatment, semen quality was already reduced in both adolescent (median sperm concentration 8x106/ml, IQR:6-116.8) and adult testicular cancer patients (median sperm concentration 18x106/ml, IQR:7-45) as well as in adolescents with a haematological malignancy (median sperm concentration: 10x106/ml, IQR:2.93±51.53; mean vitality: 55.19%, SD ± 22.85%; median progressive motility: 20%, IQR:7-50). Almost half (17/45, 38.7%) of adolescent and 18.5% (70/380) of adult samples showed oligoasthenoteratozoospermia prior to cancer treatment. Before start of treatment, adolescents who collected testicular tissue opted to cryopreserve their samples despite azoospermia to a higher rate than adults (50% vs. 20%). Not only high-risk gonadotoxic treatment, but also moderate- and low-risk treatment resulted in significant reduction of semen quality compared to cancer patients who did not receive a gonadotoxic treatment. When compared to patient samples collected before cancer treatment, sperm concentration and progressive motility significantly decreased in samples following high risk treatment in 60-70% of patients. Number of samples diagnosed with azoospermia was significantly higher in samples collected following high-risk treatment compared to samples collected before treatment. Limitations, reasons for caution We analysed retrospective data from our hospital records. We could not oversee how many cancer patients were treated during this time-period and who might have been eligible for cryopreservation. We were able to compare samples from before and after treatment only in a subgroup of patients. Wider implications of the findings Surveillance of fertility parameters, including regular spermiograms, following cancer treatment should be standard follow-up care to detect impairment, especially in men who have not cryopreserved samples previously. Even after moderate/low-risk gonadotoxic treatment, semen quality may be reduced. Simultaneously, these patients might be less likely to cryopreserve and therefore require attention. Trial registration number not applicable

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