Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Transplant Cell Ther. 2022 Aug;28(8):503.e1-503.e15. doi: 10.1016/j.jtct.2022.05.036. Epub 2022 May 26.
Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development, sexual dysfunction, and infertility. However, no systematic review exists regarding prevalence and risk factors in relation to different treatment regimens. We aimed to systematically evaluate the current evidence regarding the prevalence of male gonadal dysfunction after pediatric HSCT, related risk factors, and the diagnostic value of surrogate markers of spermatogenesis in this patient group. We searched PubMed and Embase using a combination of text words and subject terms. The eligibility screening was conducted using predefined criteria. Data were extracted corresponding to the Leydig cell compartment involved in testosterone production and the germ cell compartment involved in spermatogenesis, respectively. Subsequently, data synthesis was performed. Of 2369 identified records, 25 studies were eligible. The studies were heterogeneous in terms of included diagnoses, gonadotoxic therapy, follow-up time, and definitions of gonadal dysfunction. The data synthesis revealed a preserved Leydig cell function in patients treated with non-total body irradiation (TBI) regimens, whereas the evidence regarding the impact of TBI conditioning on Leydig cell function was conflicting. Based on surrogate markers of spermatogenesis and only limited data on semen quality, the germ cell compartment was affected in half of the patients treated with non-TBI regimens and in nearly all patients treated with TBI conditioning. Testicular irradiation as part of front-line therapy before referral to HSCT led to complete Leydig cell failure and germ cell failure. Evidence regarding the impact of diagnosis, pubertal stage at HSCT, and chronic graft-versus-host disease is limited, as is the evidence of the diagnostic value of surrogate markers of spermatogenesis. Testicular irradiation as part of front-line therapy and TBI conditioning are the main risk factors associated with male gonadal dysfunction after pediatric HSCT; however, impaired spermatogenesis is also observed in half of the patients treated with non-TBI regimens. Methodological shortcomings limit existing evidence, and future studies should include semen quality analyses, follow-up into late adulthood, and evaluation of the cumulative exposure to gonadotoxic therapy.
男性性腺功能障碍是儿科造血干细胞移植（HSCT）后的常见晚期效应，可导致青春期发育紊乱、性功能障碍和不育。然而，目前尚无关于不同治疗方案与男性性腺功能障碍的患病率和相关危险因素的系统评价。我们旨在系统评估儿科 HSCT 后男性性腺功能障碍的患病率、相关危险因素以及该患者群体中精子发生的替代标志物的诊断价值。我们使用文本词和主题词的组合在 PubMed 和 Embase 上进行了搜索。使用预设标准进行了资格筛选。分别提取了涉及睾酮产生的睾丸间质细胞区室和涉及精子发生的生精细胞区室的相关数据。随后进行了数据综合。在 2369 条鉴定记录中，有 25 项研究符合条件。这些研究在纳入的诊断、性腺毒性治疗、随访时间和性腺功能障碍的定义方面存在异质性。数据综合表明，在接受非全身照射（TBI）方案治疗的患者中，睾丸间质细胞功能得到保留，而关于 TBI 调理对睾丸间质细胞功能影响的证据则存在矛盾。基于精子发生的替代标志物，且仅有关于精液质量的有限数据，在接受非 TBI 方案治疗的患者中，有一半的患者生精细胞区室受到影响，而在接受 TBI 调理的患者中，几乎所有患者的生精细胞区室都受到影响。在转至 HSCT 前的一线治疗中进行睾丸照射会导致睾丸间质细胞完全衰竭和生精细胞衰竭。关于诊断、HSCT 时的青春期阶段和慢性移植物抗宿主病的影响的证据有限，精子发生的替代标志物的诊断价值的证据也有限。作为一线治疗的一部分进行睾丸照射和 TBI 调理是儿科 HSCT 后男性性腺功能障碍的主要危险因素；然而，在接受非 TBI 方案治疗的患者中，也有一半患者存在精子发生受损。方法学上的缺陷限制了现有证据，未来的研究应包括精液质量分析、随访至成年后期以及评估对性腺毒性治疗的累积暴露。
