Abstract：
Conventional G-banded karyotype is an essential tool for detecting chromosomal variants in patients undergoing fertility evaluation. In Australia, 15 cells are traditionally analysed or counted, to enhance detection of mosaic chromosomal variants. However, this protocol is not backed by clinical evidence. This study aims to assess the test performance of an abbreviated 5-cell karyotype analysis protocol in adult patients undergoing fertility evaluation. A retrospective review of 53,293 blood karyotype tests, performed between 2019 and 2023, was conducted on a patient cohort primarily referred by reproductive endocrinology specialists. There were 513 variants reported in this cohort. Low level mosaic variants, where the variant was observed in less than 40% of cells, were reported in 13 cases, or one in 4,100 patients. Due to reduced sensitivity for low level mosaic variants, a 5-cell protocol is estimated to have a test sensitivity of 97.3% and a negative predictive value of 99.97%. A decision-making flowchart is proposed and we show that additional chromosome analysis and/or counts would be triggered in fewer than one in 10 cases using a 5-cell protocol, whilst remaining appropriate for detecting clinically significant mosaicism. A 5-cell karyotype analysis protocol therefore maintains analytical and clinical validity in adult patients undergoing fertility-related blood karyotyping. Future research is recommended to validate these findings across laboratories and to explore their application to other clinical contexts.
摘要：
常规G带核型是检测接受生育力评估的患者染色体变异的重要工具。在澳大利亚,传统上对15个细胞进行分析或计数，增强马赛克染色体变异的检测。然而,该方案没有临床证据支持.这项研究旨在评估在接受生育力评估的成年患者中简化的5细胞核型分析方案的测试性能。53,293个血液核型测试的回顾性回顾，在2019年至2023年期间,对主要由生殖内分泌学专家转诊的患者队列进行了研究.在该队列中报告了513个变体。低级马赛克变体，在不到40%的细胞中观察到变异，报告了13例，或4100名患者中的1名。由于低水平马赛克变体的灵敏度降低，5细胞方案估计具有97.3%的测试灵敏度和99.97%的阴性预测值。提出了一个决策流程图，我们表明，使用5细胞协议，在不到10例病例中，将触发额外的染色体分析和/或计数。同时仍然适用于检测临床上显著的镶嵌性。因此，5细胞核型分析方案在接受生育相关血液核型分析的成年患者中保持分析和临床有效性。建议未来的研究在实验室中验证这些发现，并探索它们在其他临床环境中的应用。
