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儿童性腺毒性治疗后的精子发生:12例患者的随访

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

作者信息

Delgouffe E, Braye A, Vloeberghs V, Mateizel I, Ernst C, Ferster A, Devalck C, Tournaye H, Gies I, Goossens E

机构信息

Department of Reproduction, Genetics and Regenerative Medicine (RGRG), Biology of the Testis (BITE), Vrije Universiteit Brussel (VUB), Brussels, Belgium.

Brussels IVF, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

出版信息

Hum Reprod Open. 2023 Jul 31;2023(3):hoad029. doi: 10.1093/hropen/hoad029. eCollection 2023.

DOI:10.1093/hropen/hoad029
PMID:37547664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10403430/
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.

摘要

研究问题

儿童期假定的性腺毒性治疗对成年患者睾丸功能的长期影响是什么?

总结答案

尽管大多数患者在儿童期接受性腺毒性治疗12.3(2.3 - 21.0)年后睾丸体积较小且存在一定程度的生殖激素紊乱,但12例患者中有8例的精液样本中显示有活跃的精子发生。

已知信息

近几十年来,已建立了实验性睾丸组织库项目,以保护需要进行具有显著性腺毒性的化疗和/或放疗的年轻男孩未来的生育能力。尽管估计此类治疗后无精子症的风险很高,但关于成年期生殖潜能的长期数据有限。

研究设计、规模、持续时间:这项单中心前瞻性队列研究于2020年9月至2023年2月进行,涉及12名成年患者。

研究对象/材料、环境、方法:本研究在一家三级医疗中心开展,纳入了12名年轻成年人(18.1 - 28.3岁),他们在儿童期接受性腺毒性治疗前曾接受过睾丸组织库保存。所有患者均接受了生育专家的咨询和体格检查、阴囊超声以测量睾丸体积并评估睾丸实质、血液检查以评估生殖激素,以及精液分析。

主要结果及机遇的作用

12例纳入患者中有10例在性腺毒性治疗前保存了睾丸组织。9例患者睾丸体积较小,10例患者存在一定程度的生殖激素紊乱。值得注意的是,8例患者在治疗后中位时间12.3(范围2.3 - 21.0)年时显示有持续的精子发生。

局限性、谨慎的原因:本研究样本量有限,需要更大规模的研究人群进行进一步研究以验证这些初步发现。

研究结果的更广泛影响

这些发现凸显了需要开展更大规模研究人群的多中心研究,以建立未成熟睾丸组织库的通用纳入标准。

研究资金/利益冲突:本研究由弗拉芒研究基金会(G010918N)、抗癌行动和威利·格普茨科学基金(WFWG19 - 03)的研究项目提供资金支持。作者声明无利益冲突。

试验注册号

NCT04202094;https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 本研究于2019年12月6日注册,首例患者于2020年9月8日入组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acec/10403430/11c0fa7603d1/hoad029f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acec/10403430/11c0fa7603d1/hoad029f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acec/10403430/11c0fa7603d1/hoad029f1.jpg

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Eur J Cancer. 2022 Sep;173:146-166. doi: 10.1016/j.ejca.2022.05.013. Epub 2022 Aug 3.
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Immune infertility in men.男性免疫性不育
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Testicular Tissue Banking for Fertility Preservation in Young Boys: Which Patients Should Be Included?睾丸组织库用于保存年轻男孩的生育能力:哪些患者应包括在内?
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