Noninvasive assessment of embryo implantation potential using 1H NMR metabonomics

描述（由申请人提供）：多胞胎是儿童发病和长期健康受损的重要原因。体外受精（IVF）治疗通过在单个周期中移植多个胚胎显着增加了多胞胎的数量。目前的形态学标准不足以精确识别那些将成功植入的胚胎。我们基于质子核磁共振光谱（1H-NMR）的初步研究表明，对100%和0%植入病例的培养基样品记录的NMR光谱的多变量分析显示两组的统计学分离（p=0.009）。此外，将NMR光谱解卷积为培养基中存在的单个化合物的贡献表明，100%和0%植入类别之间几种化合物的浓度显著不同。基于这些全面的初步研究，我们假设可植入胚胎具有代谢特征，可以使用1D 1H-NMR在条件培养基中鉴定。为了验证我们的假设，我们建议建立基于NMR的分析用过的培养基作为一种工具，以非侵入性地预测胚胎植入成功。在具体目标1中，我们将开发统计模型，以根据记录的0%与100%植入病例的介质的1D 1H NMR光谱预测胚胎植入成功率。在具体目标2中，我们将通过将我们的基于NMR的分析方案应用于部分胚胎植入成功病例的新培养基标本来测试这些预测模型的稳健性。这将使我们能够评估模型的灵敏度，特异性和预测价值。这项研究的意义在于：（i）建立基于NMR的IVF培养基分析，作为非侵入性预测胚胎植入成功的工具，以减少多次IVF妊娠的可能性，以及（ii）获得对早期胚胎发育生物学的新见解。公共卫生相关性：体外受精（IVF）治疗导致多胞胎数量大幅增加，严重损害了孕产妇和围产期健康，并增加了社会的医疗保健费用。开发非侵入性工具，允许在每个IVF周期中选择和转移单个胚胎是至关重要的。我们提出了一个试点研究，以表征从条件培养基中的可植入胚胎的代谢谱使用质子核磁共振光谱（1H-NMR）。

DESCRIPTION (provided by applicant): Multiple births represent a significant cause of childhood morbidity and long-term compromised health. In vitro fertilization (IVF) treatment has significantly increased the number of multiple births by the transfer multiple embryos in a single cycle. Current morphological criteria are not sufficient to precisely identify those embryos that will implant successfully. Our preliminary studies based on proton nuclear magnetic resonance spectroscopy (1H-NMR) show that multivariate analysis of the NMR spectra recorded for culture media samples from 100% and 0% implantation cases revealed a statistical separation of the two groups (p=0.009). In addition, deconvolution of the NMR spectra into the contributions from individual compounds present in the culture media suggested that the concentrations of several compounds were significantly different between the 100% and 0% implantation classes. Based on these comprehensive preliminary studies, we thus hypothesize that implantable embryos have metabolic characteristics that can be identified in conditioned culture media using 1D 1H-NMR. To test our hypothesis, we propose to establish NMR-based profiling of spent culture media as a tool to non-invasively predict embryo implantation success. In Specific Aim 1 we will develop statistical models to predict embryo implantation success based on 1D 1H NMR spectra recorded for media from 0% versus 100% implantation cases. In Specific Aim 2, we will test the robustness of these predictive models by applying our protocol for NMR-based profiling to new media specimens from cases with partial embryo implantation success. This will enable us to evaluate the models' sensitivity, specificity, and predictive value. The significance of the proposed research arises from (i) establishing NMR-base profiling of IVF media as a tool to non-invasively predict embryo implantation success to reduce the likelihood of multiple IVF pregnancies, and (ii) gaining new insights into the biology of early embryo development. PUBLIC HEALTH RELEVANCE: Treatment with in vitro fertilization (IVF) has resulted in a significant increase in the number of multiple births, significantly compromising both maternal and perinatal health, and increasing health care costs to society. It is imperative to develop non-invasive tools which will allow the selection and transfer of a single embryo in each IVF cycle. We propose a pilot study to characterize the metabolic profile of implantable embryos from conditioned culture media using proton nuclear magnetic resonance spectroscopy (1H-NMR).