Korhonen Melanie, Jahnukainen Kirsi, Koskela Mikael
New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
NORDFERTIL Research Lab Stockholm, Karolinska Institute and University Hospital, Stockholm, Sweden.
Cancer. 2025 Jan 1;131(1):e35623. doi: 10.1002/cncr.35623. Epub 2024 Oct 29.
Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood.
The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964-2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n = 38), 14 years (n = 57), 16 years (n = 63), 18 years (n = 105), and in adulthood (n = 43; median age, 27 years). Testicular volumes were converted to age-specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; n = 252).
Compared with age-specific reference values, CCS generally exhibited low testicular volume z scores at ages 12-18 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation ≥1 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥12 g/m were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥4 g/m had lower paternity rates.
Testicular volume growth after prolonged follow-up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High-dose testicular radiation causes long-term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity.
儿童癌症治疗可能导致生育力低下。本研究将癌症治疗暴露情况与从青春期到成年期的睾丸体积、精子发生以及成年期的生育结果相关联。
研究人群包括255名男性儿童癌症幸存者（CCS）（存活≥5年，于1964年至2000年在赫尔辛基儿童医院确诊），他们在12岁（n = 38）、14岁（n = 57）、16岁（n = 63）、18岁（n = 105）以及成年期（n = 43；中位年龄27岁）测量了睾丸体积。将睾丸体积转换为特定年龄的z分数。此外，92名CCS在成年期（中位年龄25.2岁）提供了精液样本；并通过国家登记数据评估生育情况（评估时的平均年龄37.6岁；n = 252）。
与特定年龄的参考值相比，CCS在12至18岁时睾丸体积z分数普遍较低。仅接受化疗的CCS的睾丸体积z分数在成年期恢复到参考范围。相比之下，接受≥1格雷（Gy）睾丸辐射（中位剂量12 Gy）的患者睾丸大小未见后期恢复。睾丸辐射≥1 Gy和环磷酰胺等效剂量≥12 g/m²被确定为成年期无精子症的危险因素。接受睾丸辐射≥1 Gy且环磷酰胺等效剂量≥4 g/m²的患者生育率较低。
长期随访后的睾丸体积增长表明，仅接受化疗的CCS的精子发生可能有潜在的后期恢复。然而，烷化剂增加了长期无精子症和不育的风险。高剂量睾丸辐射导致精原细胞长期耗竭，是无精子症和不育的最强危险因素。
