Silva Cristina, Caramelo Olga, Almeida-Santos Teresa, Ribeiro Rama Ana Cristina
Centre for 20th Century Interdisciplinary Studies-CEIS20, Faculty of Pharmacy of the University of Coimbra, Rua Filipe Simões n° 33, 3000-186 Coimbra, Portugal
Gynecology Department, Coimbra Hospital and University Centre (CHUC), EPE, Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal.
Hum Reprod. 2016 Dec;31(12):2737-2749. doi: 10.1093/humrep/dew224. Epub 2016 Sep 22.
Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer?
Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes.
To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer.
STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990-2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model.
Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Müllerian hormone (patient-related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (≤40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found.
LIMITATIONS, REASONS FOR CAUTION: A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed.
The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered.
STUDY FUNDING/COMPETING INTERESTS: No external funding was received. There are no conflicts of interest to declare.
This review was registered at PROSPERO (CRD42015013494).
对于绝经前乳腺癌女性，哪些与患者、治疗或疾病相关的因素与化疗后卵巢功能恢复有关？
年龄较小以及化疗期间使用促性腺激素释放激素激动剂（GnRHa）与月经恢复显著相关，但接受紫杉烷类药物治疗的患者月经恢复的可能性较小。
迄今为止，已发表的荟萃分析仅评估了使用GnRHa作为卵巢功能恢复的一个可能因素，且结果相互矛盾。当前指南对于乳腺癌女性使用GnRHa进行生育力保护（FP）给出了不同的建议。
研究设计、规模、持续时间：对发表于英文、葡萄牙文、法文或西班牙文的研究（1990 - 2015年）、正在进行的试验或已完成的试验（1990 - 2015年）以及会议论文集（2000 - 2015年）进行系统评价和荟萃分析。
参与者/材料、环境、方法：我们检索了MEDLINE、Embase、LILACS、Scielo、Toxline和DART数据库、在线试验注册库以及会议论文集。纳入标准为研究对象为接受化疗的绝经前早期乳腺癌女性，报告了卵巢功能恢复数据并确定了与恢复相关的因素。两名作者独立筛选研究、提取数据并评估偏倚风险。从恢复事件数量估计比值比（OR）。使用随机效应模型进行荟萃分析。
纳入15篇文章。分析了五个不同因素：年龄较小和抗苗勒管激素基线水平（与患者相关的因素）、GnRHa的联合使用、在以蒽环类为基础的化疗中添加紫杉烷类以及在化疗中添加内分泌治疗（与治疗相关的因素）。月经恢复是最常用的指标。年龄较小（≤40岁）和使用GnRHa与月经恢复呈正相关（OR分别为6.07和2.03），但使用紫杉烷类药物对恢复有不利影响（OR为0.49）。研究间存在显著异质性。
局限性、需谨慎的原因：纳入研究的一个普遍局限性是使用月经作为主要恢复指标。关于GnRHa，巨大的异质性和相互矛盾的结果限制了对我们结果的解释。需要使用其他指标且随访时间更长的研究。
决定使用含紫杉烷类的化疗方案时必须考虑其对女性生育力的潜在不利影响。鉴于关于使用GnRHa激动剂的结果相互矛盾，也应考虑其他生育力保护策略。
研究资金/利益冲突：未接受外部资金。无利益冲突声明。
PROSPERO注册号：本综述已在PROSPERO注册（CRD42015013494）。
