Department of Clinical Sciences Lund, Paediatrics, Lund University, Lund, Sweden.
Paediatric Cardiology, Skåne University Hospital, Lund, Sweden.
PLoS One. 2024 Aug 12;19(8):e0308827. doi: 10.1371/journal.pone.0308827. eCollection 2024.
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.
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.
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.
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.
由于其对生活质量的影响，识别有发生卵巢早衰（POI）和生育力受损风险的儿童癌症幸存者（CCS）非常重要。本研究旨在评估成年女性 CCS 的卵巢标志物和生育结局。我们使用瑞典和 PanCareLIFE 分类来进行不孕风险分组。
纳入了 167 名 CCS 患者（中位年龄 34.6 岁，19.3-57.8 岁），中位随访时间为 25.4 年（11.6-41.3 年），并纳入了 164 名健康匹配的对照。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）和生育结局。根据给予的性腺毒性治疗，CCS 被分为不孕风险组。
CCS 的 AMH、AFC 和 OV 中位数水平较低（1.9 与 2.1ng/ml，12.0 与 13.0，6.8 与 8.0cm3），尽管仅 OV 具有统计学意义（p=0.021）。根据瑞典风险分类，40 岁以下被归类为高风险（p=0.034）和极高风险（p<0.001）的 CCS 的 AMH 水平较低。同样，AFC 在高风险（p<0.001）和极高风险组（p=0.003）中降低。所有年龄段的 CCS 生育力都呈下降趋势，尤其是极高风险组。在 167 名 CCS 中诊断出 22 例 POI，其中 14 例为高风险和极高风险组。根据 PanCareLIFE 分类的结果相似。
瑞典和 PanCareLIFE 不孕风险分类都是识别那些卵巢标志物和生育力下降以及 POI 风险增加的可靠工具。我们建议对接受高性腺毒性治疗（即环磷酰胺等效剂量≥6g/m2、卵巢放疗或干细胞移植）的患者进行生育力保存咨询，并在年轻的生殖年龄进行随访，因为存在生殖窗缩短的风险。
