Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC, USA.
Hum Reprod. 2023 Jan 5;38(1):30-45. doi: 10.1093/humrep/deac235.
What are the associations between a history of cancer and outcomes after ART?
Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART.
Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes.
STUDY DESIGN, SIZE, DURATION: We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry.
Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage.
LIMITATIONS, REASONS FOR CAUTION: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes.
Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis.
STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests.
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癌症病史与 ART 后的结局有何关联？
与没有癌症的女性相比，平均而言，患有癌症的女性胚胎移植的成功率较低，ART 后临床妊娠和活产的可能性较低。
一些小型的单机构研究表明，癌症及其治疗可能会对 ART 结局产生负面影响。
研究设计、规模、持续时间：我们对比较癌症病史女性与无癌症病史女性接受控制性卵巢刺激（COS）后 ART 结局的研究进行了系统回顾和荟萃分析。检索了 PubMed、Embase 和 Scopus 数据库，以获取截至 2021 年 6 月发表的英文原始研究。
需要报告癌症病史女性与无癌症病史女性在接受任何适应症的 ART 时接受 COS 的结果。感兴趣的结局范围从 COS 的持续时间到胚胎移植后活产的可能性。使用随机效应荟萃分析计算平均值差异和优势比（OR）及其 95%置信区间（CI）和 95%预测区间（PI）。我们通过年龄调整、ART 参考组适应症、研究地点以及乳腺癌女性和癌症治疗前开始 ART 的女性来评估异质性。我们使用视觉检查、Egger 检验和填充法来评估漏斗图的不对称性。
从 6094 条独特的记录中，有 42 项研究符合纳入标准，中位数每个研究纳入 58 名癌症女性（四分位距（IQR）= 159）和 114 名无癌症女性（IQR = 348）。与没有癌症的女性相比，平均而言，患有癌症的女性胚胎移植的成功率较低（OR：0.22；95%CI：0.07，0.74；95%PI：0.00，64.98）；临床妊娠的可能性较低（OR：0.51；95%CI：0.35，0.73；95%PI：0.19，1.35）；活产的可能性较低（OR：0.56；95%CI：0.38，0.83；95%PI：0.19，1.69）。对于 COS 持续时间、促性腺激素剂量、周期取消、总卵子和成熟卵子，观察到研究间存在大量异质性。受精率的异质性较小，但研究特异性估计不太准确。同样，胚胎数量的异质性较小，大多数研究估计癌症病史的差异较小。观察到雌二醇峰值和卵子成熟率的漏斗图不对称性。
局限性、谨慎的原因：在 11 项研究中，由于缺乏年龄组差异的充分控制，可能存在明显的混杂，并且对于大多数结局，研究间存在异质性。缺乏数据限制了我们评估癌症临床因素（例如，除乳腺癌以外的癌症、癌症分期和治疗）和 ART 周期特征（例如，新鲜与冷冻胚胎移植以及使用代孕）如何影响结局的能力。
患有癌症的女性可能不太可能在胚胎移植后怀孕和活产。需要进一步研究生殖结局和研究间异质性的来源，以提高癌症诊断后 ART 预期成功率的证据。
研究资金/竞争利益：这项研究部分得到了 R01 CA211093 和 P30 ES010126 的支持。C.M. 得到了北卡罗来纳大学林伯根癌症控制教育计划（T32 CA057726）和国家癌症研究所（F31 CA260787）的支持。J.A.R.-H. 得到了国家癌症研究所（K08 CA234333、P30 CA016672）的资助。J.A.R.-H. 报告收取 Schlesinger Group 和 Guidepoint 的咨询费。其余作者均声明不存在竞争利益。
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