BACKGROUND Female patients undergoing anticancer treatment are at elevated risk of adverse ovarian outcomes including infertility and premature ovarian insufficiency (POI), which is associated with short- and long-term health risks. Anti-Müllerian hormone (AMH) is a key biomarker of ovarian reserve, but its role prior to and after cancer treatment is less well understood. OBJECTIVE AND RATIONALE To conduct a systematic review evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment, which has become a pressing clinical issue in reproductive medicine. There are a large number of observational studies, but differences in patient groups, cancer diagnoses and study design make this a confusing field that will benefit from a thorough and robust review. SEARCH METHODS A systematic literature search for AMH in women with cancer was conducted in PubMed, Embase and Cochrane Central Register of Controlled Trials up to 1 April 2021. Bias review was conducted using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) protocol along with qualitative assessment of quality. Exploratory subgroups were established based on age, cancer type and length of follow-up. OUTCOMES Ninety-two publications (N = 9183 patients) were included in this analysis after quality and bias review. Reduced/undetectable AMH was consistently identified in 69/75 studies (92%) following chemotherapy or radiotherapy, with reductions ranging from 42% to concentrations below the limit of detection, and many reporting mean or median declines of ≥90%. Where longitudinal data were analysed (42 studies), a majority (33/42 (79%)) of studies reported at least partial recovery of AMH at follow-up, however, effect estimates were highly variable, reflecting that AMH levels were strongly impacted by anticancer treatment (i.e. the chemotherapy regimen used and the number of treatment cycles need), with recovery and its degree determined by treatment regimen, age and pre-treatment AMH level. In 16/31 (52%) publications, oligo/amenorrhoea was associated with lower post-treatment AMH consistent with impending POI, although menstruation and/or pregnancy were reported in patients with low or undetectable AMH. Long-term (>5 years) follow-up of paediatric patients following cancer treatment also found significantly lower AMH compared with control groups in 14/20 (70%) of studies, with very variable effect sizes from complete loss of AMH to full recovery depending on treatment exposure, as in adult patients. WIDER IMPLICATIONS AMH can be used to identify the damaging effect of cancer treatments on ovarian function. This can be applied to individual women, including pre-pubertal and adolescent girls, as well as comparing different treatment regimens, ages and pre-treatment AMH levels in populations of women. While there was evidence for its value in the diagnosis of POI after cancer treatment, further studies across a range of diagnoses/treatment regimens and patient ages are required to clarify this, and to quantify its predictive value. A major limitation for the use of AMH clinically is the very limited data relating post-treatment AMH levels to fertility, duration of reproductive lifespan or time to POI; analysis of these clinically relevant outcomes will be important in further research.

中文翻译：

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抗苗勒氏管激素作为癌症儿童和妇女卵巢储备和卵巢早衰的标志物：系统评价

背景：接受抗癌治疗的女性患者出现卵巢不良后果的风险较高，包括不孕和卵巢早衰（POI），这与短期和长期健康风险相关。抗苗勒氏管激素 (AMH) 是卵巢储备的关键生物标志物，但其在癌症治疗前后的作用尚不清楚。目的和原理对 AMH 作为抗癌治疗前后卵巢储备和 POI 的生物标志物进行系统评价，这已成为生殖医学中紧迫的临床问题。有大量的观察性研究，但患者群体、癌症诊断和研究设计的差异使这个领域变得令人困惑，而彻底而有力的审查将受益匪浅。检索方法 截至 2021 年 4 月 1 日，在 PubMed、Embase 和 Cochrane 对照试验中央注册库中对癌症女性 AMH 进行了系统性文献检索。使用非随机干预研究中的偏倚风险 (ROBINS- I) 协议以及质量定性评估。根据年龄、癌症类型和随访时间长度建立探索性亚组。结果 经过质量和偏倚审查后，92 篇出版物（N = 9183 名患者）被纳入本分析。69/75 项研究 (92%) 一致发现化疗或放疗后 AMH 降低/无法检测到，降低幅度从 42% 到低于检测限的浓度，许多报告平均或中位下降≥90%。分析纵向数据（42 项研究），大多数（33/42（79%））研究报告随访时 AMH 至少部分恢复，然而，效果估计差异很大，反映出 AMH 水平受到抗癌治疗（即使用的化疗方案和治疗方案）的强烈影响。需要的治疗周期数），恢复及其程度由治疗方案、年龄和治疗前AMH水平决定。在 16/31 (52%) 的出版物中，少经/闭经与治疗后较低的 AMH 相关，与即将发生的 POI 一致，尽管有报道称 AMH 较低或检测不到的患者有月经和/或怀孕。对癌症治疗后儿科患者的长期（> 5 年）随访也发现，在 14/20 (70%) 的研究中，与对照组相比，AMH 显着降低，效果大小差异很大，从 AMH 完全丧失到完全恢复，具体取决于治疗暴露程度，如成年患者。更广泛的影响 AMH 可用于确定癌症治疗对卵巢功能的损害作用。这适用于个体女性，包括青春期前和青春期女孩，以及比较女性群体的不同治疗方案、年龄和治疗前 AMH 水平。虽然有证据表明其在癌症治疗后诊断 POI 方面的价值，但需要对一系列诊断/治疗方案和患者年龄进行进一步研究来澄清这一点，并量化其预测价值。AMH 临床应用的一个主要限制是治疗后 AMH 水平与生育力相关的数据非常有限，生殖寿命的持续时间或达到 POI 的时间；对这些临床相关结果的分析对于进一步的研究非常重要。