Fertility preservation in boys: recent developments and new insights
Fertility preservation in boys: recent developments and new insights
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DOI：
10.1093/hropen/hoaa016
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发表时间：
2020-01-01
影响因子：
8.3
通讯作者：
Stukenborg, J. B.
中科院分区：
文献类型：
--
作者：
Goossens, E.;Jahnukainen, K.;Stukenborg, J. B.
背景：不育是男性癌症和其他非恶性疾病治疗的一个重要副作用。这可能是由于精原干细胞（ssc）的丧失和/或睾丸体细胞（如支持细胞、间质细胞）功能的改变。尽管精子冷冻保存是保存青春期后男性生育能力的一线方法，但这种选择并不适用于青春期前的男孩。对于不能产生精子和有失去生育能力的高风险的患者，睾丸组织冷冻现在被提议作为一种替代的实验选择来保护他们的生育能力。目的和理由：通过这篇综述，我们旨在提供最新的临床实践和实验方法，以及描述用于保存和恢复青春期前男孩生育能力丧失高风险的患者管理纳入策略。检索方法：基于参与中心的专业知识和临床实践进展的文献检索，确定了用于保存和恢复青春期前男孩生育能力丧失高风险的患者管理策略和实验方法。此外，在欧洲和北美的中心/网络中进行了一项调查，这些中心/网络发表了关于其睾丸组织库活动的论文。结果：自1994年首次发表小鼠SSC移植以来，在临床应用方面取得了显着进展：睾丸组织冷冻保存方案已经在动物模型中开发出来，现在作为一种实验性程序提供给临床患者。移植方法已适用于人类睾丸，该技术的效率和安全性正在小鼠和灵长类动物模型中进行评估。然而，重要的实际，医学和伦理问题必须解决之前恢复生育能力可以应用于临床。自2012年进行上次调查以来，实施睾丸组织冷冻保存作为保存青春期前男孩生育能力的手段有所增加。数据是从全球24个协调中心收集的，这些中心积极提供睾丸组织冷冻库，以保障男孩未来的生育能力。超过1033名年轻患者（年龄范围3个月至18岁）已经接受了睾丸组织回收和储存以保持生育能力。局限性和谨慎的原因：本综述不包括全球所有生殖中心的数据。其他中心可能会提供睾丸组织冷冻保存。因此，这些数字可能不能代表全世界生殖医学和生物学的整个领域。关于青春期前男孩生育能力保存的关键伦理问题仍然是干预的实验性质。更广泛的意义：修订后的程序可以由提供和/或开发治疗策略的多学科团队实施，以保护具有生育能力丧失高风险的青春期前男孩的生育能力。
BACKGROUND: Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility.OBJECTIVE AND RATIONALE: With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss.SEARCH METHODS: Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity.OUTCOMES: Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation.LIMITATIONS, REASONS FOR CAUTION: The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention.WIDER IMPLICATIONS: The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss.