Study question Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? Summary answer Our analysis of 36395 blastocyst biopsies across 8 genetic testing laboratories revealed that euploidy rates were significantly higher in providers reporting low rates of mosaicism. What is known already Diagnoses consistent with chromosomal mosaicism have emerged as a third category of possible options for embryo ploidy outcomes in PGT-A. However, diagnosing mosaicism using current PGT-A platforms remains hindered by several biological and technical factors. This has led to substantial variability in mosaicism rates amongst genetic testing laboratories. Furthermore, reservations regarding the clinical value of diagnosing mosaicism have led to varying practices in reporting mosaic calls amongst providers. Critically, it remains unknown whether these differences impact the number of euploid embryos available for transfer. Ultimately, this may significantly affect clinical outcomes, with important implications for PGT-A patients. Study design, size, duration Retrospective, international, multicenter cohort study of 10875 PGT-A cycles conducted between October 2015 and October 2021. A total of 18 IVF centers associated with 8 PGT-A providers, across 5 countries and 3 continents participated in the study, which included 36395 blastocysts, tested using trophectoderm biopsy and next generation sequencing (NGS). Both autologous and donation cycles were assessed. Preimplantation genetic testing for structural rearrangements (PGT-SR) cycles were excluded from the analysis. Participants/materials, setting, methods Ploidy rates were analyzed using multilevel mixed linear regression. Providers were categorized (A to H), with the most frequent provider used as the reference for statistical analysis. Analyses were adjusted for maternal age, paternal age, donor status, number of embryo biopsied and day of biopsy, as appropriate. The overall significance of categorical variables in the regression models was tested using a Chi-squared test. P-values <0.05 were considered significant. Data analysis was performed using STATA, v.15.0. Main results and the role of chance The mean maternal age(+SD) across all providers was 36.9(±5.1). As expected, maternal age and day of biopsy had a significant impact on euploidy rates (p < 0.0001). Mosaicism rates were associated with PGT-A provider and independent of all other parameters (maternal age, paternal age, donor status, number of embryos biopsied and day of biopsy). Out of the 8 providers, 7 reported chromosomal mosaicism. Amongst these 7 providers, the rate of mosaic calls varied from 2.9% to 23.9%. After adjusting for confounders, two providers reported significantly higher mosaicism rates compared to the reference (4.2%): Provider-C 10.4% (OR = 2.43, 95%CI: 1.84-4.25) and Provider-F 23.9% (OR = 4.47, 95%CI: 2.92-6.86), while euploidy and aneuploidy rates did not differ. Conversely, the chance of diagnosing mosaicism was lower in Provider-B (OR = 0.34, 95%CI: 0.22-0.54) and Provider-E (OR = 0.59, 95%CI: 0.38-0.90). Here, aneuploidy rates were comparable to the reference, yet the chance of diagnosing a euploid embryo was significantly higher: Provider-B (OR = 2.38, 95%CI: 1.87-3.03) and Provider-E (OR = 1.62, 95%CI: 1.28-2.05). Compared to the reference, euploidy rates were also higher when mosaicism was not reported: 53.5% vs. 44.2% (OR = 2.04, 95% CI: 1.60-2.59). Moreover, the chance of having at least one euploid blastocyst available for transfer significantly increased when mosaicism was not diagnosed (OR = 1.30, 95%CI: 1.13-1.50). Limitations, reasons for caution Due to the retrospective nature of the study, associations can be ascertained, however causality cannot be established. Certain parameters were not available in the dataset, therefore full elucidation of all potential confounders accounting for the variability may not be possible. Wider implications of the findings Our findings highlight the significant impact of the genetic testing provider on PGT-A results. We demonstrate that reporting mosaicism primarily comes at the expense of euploid diagnoses, raising concerns regarding the accuracy of mosaicism predictions and their impact on clinical outcomes. Moving forward, greater standardization amongst providers will be essential. Trial registration number NA

中文翻译：

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O-075 植入前基因检测提供者诊断嵌合体的隐性偏倚：对 36395 个囊胚进行大型多中心分析的结果

研究问题 嵌合体的诊断是否会影响提供非整倍体植入前基因检测 (PGT-A) 的不同提供者的倍性率？总结答案 我们对 8 个基因检测实验室的 36395 个囊胚活检的分析表明，在报告嵌合率低的提供者中，整倍体率显着更高。已知的与染色体嵌合体一致的诊断已成为 PGT-A 中胚胎倍性结果的第三类可能选择。然而，使用当前的 PGT-A 平台诊断嵌合体仍然受到一些生物学和技术因素的阻碍。这导致基因检测实验室之间嵌合率的巨大差异。此外，对诊断嵌合体的临床价值的保留导致提供者之间报告嵌合体呼叫的不同做法。至关重要的是，这些差异是否会影响可用于移植的整倍体胚胎的数量仍然未知。最终，这可能会显着影响临床结果，对 PGT-A 患者具有重要意义。研究设计、规模、持续时间 2015 年 10 月至 2021 年 10 月期间对 10875 个 PGT-A 周期进行的回顾性、国际性、多中心队列研究。共有 18 个 IVF 中心与 8 个 PGT-A 提供者相关，分布于 5 个国家和 3 个大洲。研究，其中包括 36395 个囊胚，使用滋养外胚层活检和下一代测序 (NGS) 进行了测试。评估了自体和捐赠周期。结构重排（PGT-SR）周期的植入前基因检测被排除在分析之外。参与者/材料、设置、方法使用多级混合线性回归分析倍性率。提供者被分类（A到H），最常见的提供者用作统计分析的参考。酌情根据母亲年龄、父亲年龄、供体状态、胚胎活检数量和活检天数调整分析。回归模型中分类变量的总体显着性使用卡方检验进行测试。P值＜0.05被认为是显着的。使用 STATA, v.15.0 进行数据分析。主要结果和机会的作用 所有提供者的平均孕产妇年龄（+SD）为 36.9（±5.1）。正如预期的那样，产妇年龄和活检天数对整倍体率有显着影响（p < 0.0001）。嵌合率与 PGT-A 提供者相关，并且独立于所有其他参数（母亲年龄、父亲年龄、供体状态、活检胚胎数量和活检天数）。在 8 名提供者中，7 名报告了染色体嵌合现象。在这 7 家提供商中，马赛克呼叫率从 2.9% 到 23.9% 不等。调整混杂因素后，两家供应商报告的嵌合率显着高于参考（4.2%）：Provider-C 10.4%（OR = 2.43, 95%CI: 1.84-4.25）和 Provider-F 23.9%（OR = 4.47, 95%CI：2.92-6.86），而整倍体和非整倍体率没有差异。相反，在 Provider-B (OR = 0.34, 95%CI: 0.22-0.54) 和 Provider-E (OR = 0.59, 95%CI: 0.38-0.90) 中诊断嵌合体的机会较低。这里，非整倍体率与参考值相当，但诊断整倍体胚胎的机会明显更高：Provider-B (OR = 2.38, 95%CI: 1.87-3.03) 和 Provider-E (OR = 1.62, 95%CI: 1.28) -2.05)。与参考相比，当未报告嵌合体时，整倍体率也更高：53.5% vs. 44.2% (OR = 2.04, 95% CI: 1.60-2.59)。此外，当未诊断出嵌合体时，至少有一个整倍体囊胚可供移植的机会显着增加（OR = 1.30，95%CI：1.13-1.50）。限制，谨慎的原因由于研究的回顾性，可以确定关联，但无法确定因果关系。某些参数在数据集中不可用，因此可能无法完全阐明导致变异性的所有潜在混杂因素。研究结果的更广泛意义 我们的研究结果强调了基因检测提供者对 PGT-A 结果的重大影响。我们证明，报告镶嵌现象主要是以牺牲整倍体诊断为代价的，这引起了人们对镶嵌现象预测的准确性及其对临床结果的影响的担忧。展望未来，供应商之间的更大标准化将是必不可少的。试用注册号 NA