STUDY QUESTION Should women with X chromosome abnormalities (XCAs) be recommended to have embryos selected by both morphological and cytogenetic assessment through preimplantation genetic testing (PGT) rather than morphological assessment only in conventional IVF/ICSI treatment? SUMMARY ANSWER PGT is not a preferred recommendation for women with XCAs in the absence of other PGT indications. WHAT IS KNOWN ALREADY XCAs are the most frequent sort of chromosomal aberrations in infertile women. Patients with a complete or partial absence of one X chromosome, diagnosed as Turner Syndrome (TS), demonstrate low spontaneous pregnancy rates (5–7%) and high miscarriage rates (22.8–30.8%), as well as high chances of birth defects (20%). PGT is known to improve pregnancy rates and decrease the incidence of miscarriage in couples with chromosomal aberrations such as Robertsonian and reciprocal translocations and Klinefelter Syndrome. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was conducted with 394 women with XCAs and undergoing their first oocyte retrieval and first embryo transfer cycle from June 2011 to August 2019 in the Reproductive Hospital Affiliated to Shandong University. PARTICIPANTS/MATERIALS, SETTING, METHODS Pregnancy outcomes were compared between the conventional IVF/ICSI group (n = 284) and the PGT group (n = 110) in the first fresh or frozen embryo transfer cycle for each woman with XCAs. Three platforms were applied in PGT: fluorescence in situ hybridisation (FISH, n = 34), array comparative genomic hybridisation (aCGH, n = 24) and next-generation sequencing (NGS, n = 51). The embryo aneuploidy rate and distribution of embryonic chromosomal aberrations revealed by aCGH or NGS were analysed and stratified by maternal age and type of XCAs to assess the effect of maternal XCAs on embryo karyotypes. MAIN RESULT AND THE ROLE OF CHANCE The live birth rate (LBR) per embryo transfer was similar between the PGT group and IVF/ICSI group both in the first cycle of fresh or frozen embryo transfer respectively (39.13% in PGTFISH vs 42.58% in IVF/ICSI, Padj=0.558; 66.67% in PGTFISH vs 52.08% in PGTaCGH/NGS vs 53.06% in IVF/ICSI, Padj=0.756), as was the clinical pregnancy rate (60.87% in PGTFISH vs 50.97% in IVF/ICSI, Padj =0.672; 88.89% in PGTFISH vs 58.33% in PGTaCGH/NGS vs 69.39% in IVF/ICSI, Padj =0.480) and the pregnancy loss rate (35.71% in PGTFISH vs 16.46% in IVF/ICSI, Padj =0.136; 12.50% in PGTFISH vs 10.71% in PGTaCGH/NGS vs 23.53% in IVF/ICSI, Padj =0.352). The rates of maternal and neonatal complications were also comparable between the PGT and IVF/ICSI groups with fresh and frozen transfers respectively (10.00% vs 8.85%, P = 1.000; 21.74% vs 14.55%, P = 0.272). Intriguingly, the distribution of embryonic chromosome abnormalities was more frequent on autosomes 22 (20.39%), 21 (18.45%) and 16 (17.47%), compared with the X chromosome (8.73%). LIMITATIONS, REASONS FOR CAUTION Selection bias is an inherent drawback of a retrospective study. First, our participants hosted 4.84% X chromosome mosaicism with few typical somatic anomalies of TS. Second, the incidences of history of recurrent miscarriage and abnormal offspring in the PGT group were higher than in IVF/ICSI group although binary logistic regression analysis was performed to attenuate the modifying effect of confounding factors. Third, FISH performed in this study only used X/Y probes and lacked the reference of autosome, which might have resulted in misdiagnosis and bias. Finally, intrinsic disadvantages could not be totally avoided due to the retrospective nature of this study. WIDER IMPLICATION OF THE FINDINGS In the current study, comparable pregnancy outcomes were revealed among a large cohort of women with XCAs undergoing their first cycles of PGT or conventional IVF/ICSI treatment. Moreover, the X chromosome abnormality was illustrated to cause no higher frequency of aberrations in embryos. Our data provided perspectives for genetic and reproductive counselling to XCAs individuals and their families. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by National Research and Development Plan (2016YFC1000604 and 2017YFC1001100), the National Natural Science Foundation of China (81701406), Shandong Science Fund for Distinguished Young Scholars (JQ201720), Taishan Scholars Program for Young Experts of Shandong Province (tsqn20161069) and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523 and 2016WS0368). There is no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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植入前基因检测不是 X 染色体异常患者的首选建议

研究问题 是否应建议患有 X 染色体异常 (XCA) 的女性通过植入前基因检测 (PGT) 进行形态学和细胞遗传学评估来选择胚胎，而不是仅在常规 IVF/ICSI 治疗中进行形态学评估？总结 答案 对于没有其他 PGT 适应症的 XCA 女性，PGT 不是首选建议。已知情况 XCA 是不孕女性中最常见的染色体畸变类型。一条 X 染色体完全或部分缺失的患者，被诊断为特纳综合征 (TS)，表现出低自然妊娠率 (5-7%) 和高流产率 (22.8-30.8%)，以及出生缺陷的高几率（20%）。众所周知，PGT 可以提高妊娠率并降低患有染色体畸变（例如罗伯逊易位和相互易位以及克氏综合征）的夫妇的流产率。研究设 参与者/材料、设置、方法 在每位患有 XCA 的女性的第一个新鲜或冷冻胚胎移植周期中，比较了传统 IVF/ICSI 组 (n = 284) 和 PGT 组 (n = 110) 的妊娠结局。PGT 中应用了三个平台：荧光原位杂交（FISH，n = 34），阵列比较基因组杂交（aCGH，n = 24）和下一代测序（NGS，n = 51）。分析aCGH或NGS揭示的胚胎非整倍体率和胚胎染色体畸变分布，并按母体年龄和XCA类型分层，以评估母体XCA对胚胎核型的影响。主要结果和机会的作用 PGT 组和 IVF/ICSI 组在新鲜或冷冻胚胎移植的第一个周期中每次胚胎移植的活产率 (LBR) 分别相似（PGTFISH 为 39.13%，IVF 为 42.58% /ICSI，Padj=0.558；PGTFISH 为 66.67%，PGTaCGH/NGS 为 52.08%，IVF/ICSI 为 53.06%，Padj=0.756），临床妊娠率也是如此（PGTFISH 为 60.87%，IVF/ICSI 为 50.97%， Padj =0.672；PGTFISH 88.89% vs PGTaCGH/NGS 58.33% vs IVF/ICSI 69.39%，Padj =0.480）和流产率（PGTFISH 35.71% vs IVF/ICSI 16.46%，帕杰=0.136；PGTFISH 为 12.50%，PGTaCGH/NGS 为 10.71%，IVF/ICSI 为 23.53%，Padj = 0.352）。孕产妇和新生儿并发症的发生率在 PGT 和 IVF/ICSI 组之间也分别具有可比性（10.00% vs 8.85%，P = 1.000；21.74% vs 14.55%，P = 0.272）。有趣的是，与 X 染色体 (8.73%) 相比，胚胎染色体异常的分布在常染色体 22 (20.39%)、21 (18.45%) 和 16 (17.47%) 上更为频繁。局限性、谨慎的原因 选择偏倚是回顾性研究的固有缺陷。首先，我们的参与者有 4.84% 的 X 染色体嵌合体，很少有典型的 TS 体细胞异常。第二，尽管进行二元逻辑回归分析以减弱混杂因素的修正作用，但 PGT 组的反复流产史和异常后代的发生率高于 IVF/ICSI 组。第三，本研究中进行的FISH仅使用X/Y探针，缺乏常染色体的参考，可能导致误诊和偏倚。最后，由于本研究的回顾性，无法完全避免内在缺点。研究结果的更广泛意义 在目前的研究中，在接受第一个周期的 PGT 或常规 IVF/ICSI 治疗的一大群 XCA 女性中揭示了类似的妊娠结局。此外，X 染色体异常被证明不会导致胚胎中出现更高频率的畸变。我们的数据为 XCA 个人及其家庭的遗传和生殖咨询提供了视角。研究资助/竞争兴趣（S） 这项工作得到了国家研究发展计划（2016YFC1000604 和 2017YFC1001100）、国家自然科学基金（81701406）、山东省杰出青年科学基金（JQ201720）、泰山学者计划山东省青年专家（tsqn20161069）和山东省医疗卫生技术发展计划项目（202005010520、202005010523和2016WS0368）。没有利益冲突需要申报。试用注册号 不适用。研究资助/竞争兴趣（S） 这项工作得到了国家研究发展计划（2016YFC1000604 和 2017YFC1001100）、国家自然科学基金（81701406）、山东省杰出青年科学基金（JQ201720）、泰山学者计划山东省青年专家（tsqn20161069）和山东省医疗卫生技术发展计划项目（202005010520、202005010523和2016WS0368）。没有利益冲突需要申报。试用注册号 不适用。研究资助/竞争兴趣（S） 这项工作得到了国家研究发展计划（2016YFC1000604 和 2017YFC1001100）、国家自然科学基金（81701406）、山东省杰出青年科学基金（JQ201720）、泰山学者计划山东省青年专家（tsqn20161069）和山东省医疗卫生技术发展计划项目（202005010520、202005010523和2016WS0368）。没有利益冲突需要申报。试用注册号 不适用。山东省泰山学者青年专家计划（tsqn20161069）和山东省医疗卫生技术发展计划项目（202005010520、202005010523和2016WS0368）。没有利益冲突需要申报。试用注册号 不适用。山东省泰山学者青年专家计划（tsqn20161069）和山东省医疗卫生技术发展计划项目（202005010520、202005010523和2016WS0368）。没有利益冲突需要申报。试用注册号 不适用。