BACKGROUND In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41–1.38)) or NC (aOR 1.29 (95% CI 0.69–2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09–1.85)) and NC (OR 2.46 (95% CI 1.52–3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07–3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.

中文翻译：

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ICSI与染色体异常关系的系统评价和荟萃分析

背景 在引入 ICSI 后的十年中，与自然受孕 (NC) 的儿童和通过标准体外​​受精受孕的孩子。对所观察到的患病率增加的解释尚不清楚，有人认为这反映了父母因素（例如年龄或精子质量）或者是 ICSI 程序本身的结果。多年来，ICSI 治疗的程序、患者组和适应症都发生了变化。目的和理由 本系统评价和荟萃分析的目的是评估 ICSI 妊娠和儿童染色体异常的患病率，并检查与标准 IVF 和 NC 相比可能增加的风险。搜索方法 搜索了截至 2020 年 10 月的 Pubmed、Embase、Cochrane 图书馆和 Web of Science。主要结果测量是整体染色体异常和从头异常（包括性染色体异常和常染色体异常）。次要结果是遗传异常。我们遵循 PRISMA 指南并进行了相关的荟萃分析。结果 搜索包括 4648 篇文章，其中 27 篇符合纳入标准，19 篇被纳入定量综合（荟萃分析）。研究之间染色体异常的患病率差异很大，这可能是由于样本量和患者人口统计数据的巨大差异所致。只有五项研究有资格对调整后的数据进行汇总分析。所有研究都存在严重的偏倚风险。汇总调整数据的结果显示，在将 ICSI 与标准 IVF（aOR 0.75（95% CI 0.41-1.38））或 NC（aOR 1.29（95% CI 0.69-2.43））进行比较时，没有证据表明整体染色体异常的风险增加。相比之下，对未调整数据的荟萃分析显示，与标准 IVF（OR 1.42（95% CI 1.09–1.85））和 NC（OR 2.46（95% CI 1.52–3.99））相比，ICSI 中总体染色体异常的风险增加与 NC 相比，ICSI 从头异常的风险增加（OR 2.62 (95% CI 2.07–3.31)）。然而，基于非常低确定性的证据，结论仍然是，没有迹象表明 ICSI 后代染色体异常的风险增加。如果在选定的 ICSI 后代中存在染色体异常风险增加，则绝对风险仍然很小。更广泛的影响 本综述提供了关于 ICSI 与后代染色体异常之间关系的现有证据的广泛概述。我们强调需要通过系统的细胞遗传学检测进行精心设计的大型、前瞻性、对照研究。现有数据是有限的，而且在许多情况下，受到严重程度的偏见的影响。绝对风险仍然很小。更广泛的影响 本综述提供了关于 ICSI 与后代染色体异常之间关系的现有证据的广泛概述。我们强调需要通过系统的细胞遗传学检测进行精心设计的大型、前瞻性、对照研究。现有数据是有限的，而且在许多情况下，受到严重程度的偏见的影响。绝对风险仍然很小。更广泛的影响 本综述提供了关于 ICSI 与后代染色体异常之间关系的现有证据的广泛概述。我们强调需要通过系统的细胞遗传学检测进行精心设计的大型、前瞻性、对照研究。现有数据是有限的，而且在许多情况下，受到严重程度的偏见的影响。