Abstract

BACKGROUND

Endometrial cancer is common and usually occurs after menopause, but the number of women diagnosed during reproductive age is increasing. The standard treatment including hysterectomy is effective but causes absolute uterine factor infertility. In order to avoid or postpone surgery, conservative management of endometrial cancer (CMEC) has been proposed for younger women who want to retain their fertility.

OBJECTIVE AND RATIONALE

The main objective of this study was to estimate the chances of pregnancy and live birth for women with early-stage endometrial cancer (EEC) who are managed conservatively for fertility preservation.

SEARCH METHODS

The PRISMA recommendations for systematic reviews and meta-analyses were followed. Structured searches were performed in PubMed, Embase and the Cochrane Library, from inception until 13 June 2021. Inclusion was based on the following criteria: group or subgroup of women with Clinical Stage IA, well-differentiated, endometrioid endometrial cancer (from now on, EEC); CMEC for fertility preservation; and reported frequencies of women achieving pregnancy and/or live birth after CMEC. The following exclusion criteria applied: impossibility to isolate/extract outcome data of interest; second-line CMEC for persistent/recurrent disease; CMEC in the presence of synchronous tumours; case reports; non-original or duplicated data; and articles not in English. Qualitative synthesis was performed by means of tabulation and narrative review of the study characteristics. Study quality was assessed with an ad hoc instrument and several moderator and sensitivity analyses were performed.

OUTCOMES

Out of 1275 unique records, 133 were assessed in full-text and 46 studies were included in the review. Data from 861 women with EEC undergoing CMEC were available. Progestin-based treatment was reported in all but three studies (93.5%; 836 women). Complete response to treatment was achieved in 79.7% of women, with 35.3% of them having a disease recurrence during follow-up. Of 286 pregnancies obtained after CMEC; 69.4% led to live birth (9% of them multiple births) and 66.7% were achieved through fertility treatment. Based on random-effects meta-analyses, women treated with progestin-based CMEC have a 26.7% chance of achieving pregnancy (95% CI 21.3–32.3; I² = 53.7%; 42 studies, 826 women) and a 20.5% chance to achieve a live birth (95% CI 15.7–25.8; I² = 40.2%; 39 studies, 650 women). Sample size, average age, publication year, study design and quality score were not associated with the outcomes of progestin-based CMEC in moderator analyses with meta-regression. However, mean follow-up length (in months) was positively associated with the chances of pregnancy (regression coefficient [B] = 0.003; 95% CI 0.001–0.005; P = 0.006) and live birth (B = 0.005; 95% CI 0.003–0.007; P < 0.001). In sensitivity analyses, the highest chances of live birth were estimated in subsets of studies including only women of age 35 or younger (30.7%), the combination of progestins with hysteroscopic resection (30.7%), or at least 3 years of follow-up (42.4%).

WIDER IMPLICATIONS

Progestin-based CMEC is viable for women with well-differentiated, Clinical Stage 1A, endometrioid endometrial cancer who want to preserve their fertility, but there is room for improvement as only one-fifth of them are estimated to achieve live birth according to this meta-analysis. Further investigations on prognosis-driven selection, hysteroscopic resection and long-term surveillance are arguably needed to improve the reproductive outcomes of CMEC.

中文翻译：

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接受保守治疗的早期子宫内膜癌妇女的妊娠和活产几率：一项系统评价和荟萃分析

摘要

背景

子宫内膜癌很常见，通常发生在绝经后，但在育龄期确诊的女性人数正在增加。包括子宫切除术在内的标准治疗是有效的，但会导致绝对子宫因素不孕。为了避免或推迟手术，已建议对希望保留生育能力的年轻女性进行子宫内膜癌保守治疗 (CMEC)。

目标和理由

本研究的主要目的是评估为保留生育力而采取保守治疗的早期子宫内膜癌 (EEC) 女性怀孕和活产的几率。

搜索方法

遵循了 PRISMA 对系统评价和荟萃分析的建议。从开始到 2021 年 6 月 13 日，在 PubMed、Embase 和 Cochrane 图书馆进行了结构化搜索。纳入基于以下标准：具有临床 IA 期、分化良好的子宫内膜样子宫内膜癌的女性组或亚组（从现在开始，欧洲经济共同体）; CMEC生育力保存；并报告了 CMEC 后妇女怀孕和/或活产的频率。应用以下排除标准：不可能分离/提取感兴趣的结果数据；用于持续性/复发性疾病的二线 CMEC；存在同步肿瘤的 CMEC；病例报告；非原始或重复数据；和非英文文章。通过对研究特征进行制表和叙述性回顾来进行定性综合。研究质量通过以下方式评估进行了临时仪器和一些调节剂和敏感性分析。

结果

在 1275 条独特的记录中，有 133 条进行了全文评估，46 项研究被纳入审查。来自 861 名接受 CMEC 的 EEC 女性的数据可用。除三项研究（93.5%；836 名女性）外，所有研究均报告了基于孕激素的治疗​​。79.7% 的女性对治疗有完全反应，其中 35.3% 的女性在随访期间疾病复发。CMEC 后获得的 286 例妊娠；69.4% 导致活产（其中 9% 为多胞胎），66.7% 通过生育治疗实现。根据随机效应荟萃分析，接受基于孕激素的 CMEC 治疗的女性有 26.7% 的机会怀孕（95% CI 21.3–32.3；I ²  = 53.7%；42 项研究，826 名女性）和 20.5% 的机会实现活产（95% CI 15.7–25.8；I ² = 40.2%；39 项研究，650 名女性）。样本量、平均年龄、发表年份、研究设计和质量评分与基于孕激素的 CMEC 在元回归调节分析中的结果无关。然而，平均随访时间（以月为单位）与怀孕几率（回归系数 [ B ] = 0.003；95% CI 0.001–0.005；P  = 0.006）和活产率（B  = 0.005；95% CI ）呈正相关0.003–0.007；P  < 0.001）。在敏感性分析中，估计活产几率最高的研究子集仅包括 35 岁或以下的女性 (30.7%)、孕激素联合宫腔镜切除术 (30.7%) 或至少 3 年的随访(42.4%)。

更广泛的影响

基于孕激素的 CMEC 对于患有高分化、临床 1A 期、子宫内膜样子宫内膜癌并希望保留生育能力的女性是可行的，但仍有改进的空间，因为根据该元数据，估计其中只有五分之一的女性能够活产-分析。可以说需要进一步研究预后驱动的选择、宫腔镜切除术和长期监测，以改善 CMEC 的生殖结果。