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曾接受小儿恶性肿瘤治疗的青春期女性及年轻女性:评估卵巢储备及性腺毒性风险分层,以早期识别不孕风险增加的患者。

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk.

作者信息

Parissone Francesca, Di Paola Rossana, Balter Rita, Garzon Simone, Zaffagnini Stefano, Neri Maria, Vitale Virginia, Tridello Gloria, Cesaro Simone

机构信息

Obstetrics and Gynecology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

出版信息

J Pediatr Endocrinol Metab. 2020 Oct 19;34(1):25-33. doi: 10.1515/jpem-2020-0272. Print 2021 Jan 27.

DOI:10.1515/jpem-2020-0272
PMID:33068384
Abstract

OBJECTIVES

Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs.

METHODS

A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile).

RESULTS

Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001).

CONCLUSIONS

In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

摘要

目的

儿童和青少年癌症幸存者(CACSs)存在不良生殖结局的风险。促卵泡生成素(FSH)水平评估是诊断卵巢早衰(POI)最常用的检测方法,而抗苗勒管激素(AMH)和窦卵泡计数(AFC)已被提议作为卵巢储备标志物。我们评估了这些标志物与CACSs治疗性腺毒性风险(GR)之间的相关性。

方法

共纳入55例女性CACSs。根据基于疾病和治疗以及环磷酰胺等效剂量评分的分类,将GR分为低、中、高三个等级。测定FSH、AMH和AFC。POI定义为闭经且FSH>30 IU/L。对于其余患者,卵巢储备功能减退(DOR)定义为AMH<第5百分位数。还考虑了文献中作为DOR标志物提出的FSH和AFC临界值(FSH>10 IU/L或>第95百分位数;AFC<8或<第5百分位数)。

结果

23例(41.8%)患者的卵巢储备功能受损:14例为DOR,9例为确诊POI。结果显示GR分类是卵巢储备功能良好预测指标,高危组AMH和AFC显著降低。AFC与AMH直接相关(r = 0.75,p<0.001)。

结论

在CACSs中,GR分类与治疗后AMH和AFC相关。这些是早期识别可能从生殖和生育力保存咨询中受益的DOR年轻患者的有用工具。需要进一步研究以确定该人群中从DOR进展为POI发生率和时间。

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