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Abstract：
BACKGROUND: To identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping.
METHODS: 167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups.
RESULTS: The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar.
CONCLUSIONS: Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.
METHODS: 167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups.
RESULTS: The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar.
CONCLUSIONS: Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.
摘要：
背景：鉴于其对生活质量的影响，确定处于过早卵巢功能不全（POI）和生育力受损风险的儿童癌症幸存者（CCS）很重要。这项研究的目的是评估成年女性CCS的卵巢标志物和生育结果。我们使用瑞典语和PanCareLIFE分类进行不孕症风险分组。
方法：167个CCS，中位年龄为34.6岁（19.3-57.8），中位随访时间为25.4年（11.6-41.3），本横断面研究包括164名健康匹配对照.我们评估了抗苗勒管激素（AMH）水平，窦卵泡计数（AFC），卵巢体积(OV),和生育结果。根据给予的性腺毒性治疗，CCS被分为不孕风险组。
结果：AMH的中位数水平，CCS中的AFC和OV较低（1.9与2.1ng/ml,12.0vs.13.0,6.8vs.8.0cm3)与对照相比，尽管仅对OV具有统计学意义（p=0.021）。对于那些被归类为不孕症的高风险（p=0.034）和非常高风险（p<0.001）的患者，<40年的CCS中的AMH水平较低，根据瑞典的风险分类。同样，高风险组（p<0.001）和极高风险组（p=0.003）的AFC降低。所有年龄段的CCS都显示出生育率下降的趋势，尤其是高危人群。POI在22/167CCS中被诊断出，其中14人属于高危和极高危人群。根据PanCareLIFE分类的结果相似。
结论：瑞典和PanCareLIFE不孕症风险分类是识别卵巢标志物和生育能力降低风险的可靠工具，以及POI。我们建议对接受高度性腺毒性治疗的患者进行生育力保留咨询(即，环磷酰胺等效剂量≥6g/m2，放疗暴露于卵巢或干细胞移植），由于生殖窗口缩短的风险，在年轻的生育年龄进行随访。
方法：167个CCS，中位年龄为34.6岁（19.3-57.8），中位随访时间为25.4年（11.6-41.3），本横断面研究包括164名健康匹配对照.我们评估了抗苗勒管激素（AMH）水平，窦卵泡计数（AFC），卵巢体积(OV),和生育结果。根据给予的性腺毒性治疗，CCS被分为不孕风险组。
结果：AMH的中位数水平，CCS中的AFC和OV较低（1.9与2.1ng/ml,12.0vs.13.0,6.8vs.8.0cm3)与对照相比，尽管仅对OV具有统计学意义（p=0.021）。对于那些被归类为不孕症的高风险（p=0.034）和非常高风险（p<0.001）的患者，<40年的CCS中的AMH水平较低，根据瑞典的风险分类。同样，高风险组（p<0.001）和极高风险组（p=0.003）的AFC降低。所有年龄段的CCS都显示出生育率下降的趋势，尤其是高危人群。POI在22/167CCS中被诊断出，其中14人属于高危和极高危人群。根据PanCareLIFE分类的结果相似。
结论：瑞典和PanCareLIFE不孕症风险分类是识别卵巢标志物和生育能力降低风险的可靠工具，以及POI。我们建议对接受高度性腺毒性治疗的患者进行生育力保留咨询(即，环磷酰胺等效剂量≥6g/m2，放疗暴露于卵巢或干细胞移植），由于生殖窗口缩短的风险，在年轻的生育年龄进行随访。
