BACKGROUND

Successful embryo implantation is a complex process that requires the coordination of a series of events, involving both the embryo and the maternal endometrium. Key to this process is the intricate cascade of molecular mechanisms regulated by endocrine, paracrine and autocrine modulators of embryonic and maternal origin. Despite significant progress in ART, implantation failure still affects numerous infertile couples worldwide and fewer than 10% of embryos successfully implant. Improved selection of both the viable embryos and the optimal endometrial phenotype for transfer remains crucial to enhancing implantation chances. However, both classical morphological embryo selection and new strategies incorporated into clinical practice, such as embryonic genetic analysis, morphokinetics or ultrasound endometrial dating, remain insufficient to predict successful implantation. Additionally, no techniques are widely applied to analyse molecular signals involved in the embryo–uterine interaction. More reliable biological markers to predict embryo and uterine reproductive competence are needed to improve pregnancy outcomes. Recent years have seen a trend towards ‘omics’ methods, which enable the assessment of complete endometrial and embryonic molecular profiles during implantation. Omics have advanced our knowledge of the implantation process, identifying potential but rarely implemented biomarkers of successful implantation.

OBJECTIVE AND RATIONALE

Differences between the findings of published omics studies, and perhaps because embryonic and endometrial molecular signatures were often not investigated jointly, have prevented firm conclusions being reached. A timely review summarizing omics studies on the molecular determinants of human implantation in both the embryo and the endometrium will help facilitate integrative and reliable omics approaches to enhance ART outcomes.

SEARCH METHODS

In order to provide a comprehensive review of the literature published up to September 2019, Medline databases were searched using keywords pertaining to omics, including ‘transcriptome’, ‘proteome’, ‘secretome’, ‘metabolome’ and ‘expression profiles’, combined with terms related to implantation, such as ‘endometrial receptivity’, ‘embryo viability’ and ‘embryo implantation’. No language restrictions were imposed. References from articles were also used for additional literature.

OUTCOMES

Here we provide a complete summary of the major achievements in human implantation research supplied by omics approaches, highlighting their potential to improve reproductive outcomes while fully elucidating the implantation mechanism. The review highlights the existence of discrepancies among the postulated biomarkers from studies on embryo viability or endometrial receptivity, even using the same omic analysis.

WIDER IMPLICATIONS

Despite the huge amount of biomarker information provided by omics, we still do not have enough evidence to link data from all omics with an implantation outcome. However, in the foreseeable future, application of minimally or non-invasive omics tools, together with a more integrative interpretation of uniformly collected data, will help to overcome the difficulties for clinical implementation of omics tools. Omics assays of the embryo and endometrium are being proposed or already being used as diagnostic tools for personalised single-embryo transfer in the most favourable endometrial environment, avoiding the risk of multiple pregnancies and ensuring better pregnancy rates.

中文翻译：

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鉴定可预测成功胚胎植入的生物标记物：将单个OMIC应用于多个OMIC以改善生殖结果

背景

成功的胚胎植入是一个复杂的过程，需要协调一系列事件，涉及胚胎和母体子宫内膜。该过程的关键是复杂的分子机制级联，这些分子机制受胚胎和母亲起源的内分泌，旁分泌和自分泌调节剂调控。尽管抗逆转录病毒疗法取得了重大进展，但植入失败仍然影响着全世界的许多不育夫妇，成功植入的胚胎不到10％。活胚和最佳子宫内膜表型转移的更好选择对于提高植入机率仍然至关重要。但是，经典的形态学胚胎选择和临床实践中采用的新策略，例如胚胎遗传分析，形态动力学或超声内膜约会，仍然不足以预测成功的植入。此外，没有任何技术被广泛应用于分析与胚胎-子宫相互作用有关的分子信号。需要更可靠的生物学标记来预测胚胎和子宫的生殖能力，以改善妊娠结局。近年来，已经出现了“组学”方法的趋势，该方法能够在植入过程中评估完整的子宫内膜和胚胎分子特征。Omics进一步提高了我们对植入过程的了解，确定了成功植入的潜在但很少实施的生物标志物。需要更可靠的生物学标记来预测胚胎和子宫的生殖能力，以改善妊娠结局。近年来，已经出现了“组学”方法的趋势，该方法能够在植入过程中评估完整的子宫内膜和胚胎分子特征。Omics进一步提高了我们对植入过程的了解，确定了成功植入的潜在但很少实施的生物标志物。需要更可靠的生物学标记来预测胚胎和子宫的生殖能力，以改善妊娠结局。近年来，已经出现了“组学”方法的趋势，该方法能够在植入过程中评估完整的子宫内膜和胚胎分子特征。Omics进一步提高了我们对植入过程的了解，确定了成功植入的潜在但很少实施的生物标志物。

目的和理由

已发表的组学研究结果之间的差异，可能是因为通常没有共同研究胚胎和子宫内膜的分子特征，因此无法得出明确的结论。对有关胚胎和子宫内膜中人类植入的分子决定因素的组学研究进行及时的综述，将有助于促进综合可靠的组学方法，以提高抗逆转录病毒疗法的疗效。

搜索方法

为了全面审查截至2019年9月发表的文献，Medline数据库使用与组学相关的关键词进行搜索，包括``转录组''，``蛋白质组''，``秘密组''，``代谢组''和``表达谱''，以及与植入有关的术语，例如“子宫内膜容受性”，“胚胎生存力”和“胚胎植入”。没有语言限制。文章的参考文献也用于其他文献。

结果

在这里，我们提供了由组学方法提供的人类植入研究的主要成就的完整摘要，着重介绍了它们在充分阐明植入机制的同时改善生殖结果的潜力。这篇综述强调了关于胚胎生存力或子宫内膜容受性研究的假设生物标志之间存在差异，即使使用相同的组学分析也是如此。

暗示

尽管组学提供了大量的生物标志物信息，但我们仍然没有足够的证据将所有组学的数据与植入结果联系起来。然而，在可预见的将来，最小化或非侵入性的组学工具的应用，以及对统一收集的数据的更综合的解释，将有助于克服组学工具在临床上的实施困难。胚胎和子宫内膜的Omics检测已被提议或已被用作诊断工具，用于在最有利的子宫内膜环境中进行个性化单胚转移，从而避免了多次怀孕的风险并确保更高的怀孕率。