Preimplantation genetic testing for aneuploidy

非整倍性的植入前遗传检测
  • 文章类型: Meta-Analysis
    非整倍体的植入前遗传测试(PGT-A)是一项新兴技术,旨在鉴定用于移植的整倍体胚胎,降低胚胎染色体异常的风险。然而,PGT-A在复发性妊娠失败(RPF)患者中的临床益处,特别是在年轻的RPF患者中,仍然不确定。
    这项荟萃分析旨在确定接受PGT-A的RPF患者与未接受PGT-A的患者相比是否具有更好的临床结果,从而评估PGT-A在临床实践中的价值。
    我们系统地搜索了PubMed,Cochrane图书馆,中国国家知识基础设施(CNKI),万方数据,和2002年至2022年的中国技术期刊(VIP)VIP数据库。该荟萃分析包括13项已发表的研究,涉及使用PGT-A筛查的930名RPF患者和不使用PGT-A筛查的1,434名RPF患者。根据PGT-A(n=1,015)和不含PGT-A(n=1,799)的胚胎移植评估临床结果。
    与体外受精(IVF)/卵胞浆内单精子注射(ICSI)组相比,PGT-A组表现出更好的临床结局。PGT-A组的植入率(IR)明显更高(RR=2.01,95%CI:[1.73;2.34]),临床妊娠率(CPR)(RR=1.53,95%CI:[1.36;1.71]),持续妊娠率(OPR)(RR=1.76,95%CI:[1.35;2.29]),活产率(LBR)(RR=1.75,95%CI:[1.51;2.03]),显著降低临床流产率(CMR)(RR=0.74,95%CI:[0.54;0.99])。基于患者年龄(35岁以下和35岁或以上)的亚组分析显示,与IVF/ICSI组相比,两个PGT-A亚组的CPR(P<0.01)和LBR(P<0.05)值均明显更好。
    这项荟萃分析表明,PGT-A在RPF患者中,与改善的临床结果相关,包括更高的IR,CPR,OPR,和LBR值,与IVF/ICSI组相比,CMR较低。这些发现支持PGT-A在RPF患者中的积极临床应用。
    http://INPLASY.com,标识符INPLASY202320118。
    Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic chromosomal abnormalities. However, the clinical benefits of PGT-A in recurrent pregnancy failure (RPF) patients, particularly in young RPF patients, remains uncertain.
    This meta-analysis aimed to determine whether RPF patients undergoing PGT-A had better clinical outcomes compared to those not undergoing PGT-A, thus assessing the value of PGT-A in clinical practice.
    We systematically searched PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals (VIP) from 2002 to 2022. Thirteen published studies involving 930 RPF patients screened using PGT-A and over 1,434 RPF patients screened without PGT-A were included in this meta-analysis. Clinical outcomes were evaluated based on embryo transfers after PGT-A (n=1,015) and without PGT-A (n=1,799).
    The PGT-A group demonstrated superior clinical outcomes compared to the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) group. The PGT-A group had a significantly higher implantation rate (IR) (RR=2.01, 95% CI: [1.73; 2.34]), clinical pregnancy rate (CPR) (RR=1.53, 95% CI: [1.36; 1.71]), ongoing pregnancy rate (OPR) (RR=1.76, 95% CI: [1.35; 2.29]), live birth rate (LBR) (RR=1.75, 95% CI: [1.51; 2.03]), and significantly lower clinical miscarriage rate (CMR) (RR=0.74, 95% CI: [0.54; 0.99]). Subgroup analysis based on patient age (under 35 years and 35 years or older) showed that both PGT-A subgroups had significantly better CPR (P<0.01) and LBR (P<0.05) values compared to the IVF/ICSI groups.
    This meta-analysis demonstrates that PGT-A in RPF patients, is associated with improved clinical outcomes, including higher IR, CPR, OPR, and LBR values, and lower CMR compared to the IVF/ICSI group. These findings support the positive clinical application of PGT-A in RPF patients.
    http://INPLASY.com, identifier INPLASY 202320118.
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  • 文章类型: Meta-Analysis
    染色体镶嵌成为植入前基因检测(PGT)中的常见现象。进行此荟萃分析以研究哪些染色体镶嵌性特征与胚胎移植相容。
    搜索PubMed数据库后,Embase,CCTR和相关审查,直到2021年5月。两名评审员提取了相关信息,并通过纽卡斯尔-渥太华量表独立评估了研究质量。使用固定或随机效应模型计算临床结果的概要奇数无线电(OR)。网络荟萃分析比较了不同染色体的临床结果。
    总共包括6项研究,其中1,106个周期的单镶嵌胚胎转移。显著结果的植入率(IR),流产率(MR),当比较镶嵌水平<50%和≥50%的胚胎时,观察到持续妊娠/活产率(OP/LBR)[OR1.42,95%CI(1.06,1.89);OR0.45,95%CI(0.27,0.75);OR1.74,95%CI(1.28,2.37)],和镶嵌性胚胎,仅影响节段染色体,仅涉及整个染色体[OR1.31,95%CI(1.01,1.71);OR0.57,95%CI(0.36,0.93);OR1.51,95%CI(1.15,2.00)]。只有镶嵌收益或损失的胚胎具有比复杂镶嵌显著更高的IR和OP/LBR[增益与复杂:OR1.75,95%CI(1.20,2.54);OR1.73,95%CI(1.16,2.58)。损失与复杂:OR1.90,95%CI(1.34,2.71);OR2.10,95%CI(1.44,3.07)]。与涉及三个或更多个染色体的花叶胚相比,仅涉及一个染色体的花叶胚具有IR和OP/LBR的显着有利结果[OR1.76,95%CI(1.23,2.52);OR1.86,95%CI(1.25,2.78)]。Chr.7,Chr。2,Chr。1,Chr。18,Chr。11,Chr。X,Chr.13,Chr。14,Chr.12和Chr。9被认为是用于转移的镶嵌胚胎的优先染色体。
    该分析支持镶嵌水平≥50%的胚胎,涉及整个染色体,多个马赛克异常与更差的妊娠结局相关.50%的镶嵌水平可以用作评估镶嵌胚的阈值。
    Chromosomal mosaicism becomes a common phenomenon in Preimplantaion genetic testing (PGT). This meta-analysis was conducted to study which feature of chromosomal mosaicism was compatible for embryo transfer.
    After searching the database PubMed, Embase, CCTR and related reviews up until May 2021. Two reviewers extracted relevant information and assessed study quality by the Newcastle-Ottawa scale independently. Summary Odd Radios (OR) were calculated using fixed- or random-effects models for clinical outcomes. A network meta-analysis compared the clinical outcomes of different chromosomes.
    A total of six studies with 1,106 cycles of single mosaic embryo transferred were included. Significant results of implantation rate (IR), miscarriage rate (MR), and ongoing pregnancy/live birth rate (OP/LBR) were observed when comparing embryos with mosaicism level < 50% and ≥ 50% [OR 1.42, 95% CI (1.06, 1.89); OR 0.45, 95% CI (0.27, 0.75); OR 1.74, 95% CI (1.28, 2.37)], and embryos with mosaicism with only affecting segmental chromosome(s) and only involving whole chromosome(s) [OR 1.31, 95% CI (1.01, 1.71); OR 0.57, 95% CI (0.36, 0.93); OR 1.51, 95% CI (1.15, 2.00)]. Embryos with only mosaic gains or losses had significant higher IR and OP/LBR than complex mosaicism [Gains vs complex: OR 1.75, 95% CI (1.20, 2.54); OR 1.73, 95% CI (1.16, 2.58). Losses vs complex: OR 1.90, 95% CI (1.34, 2.71); OR 2.10, 95% CI (1.44, 3.07)]. Mosaic embryos with only one chromosome involved had significant favorable outcomes of IR and OP/LBR than with three or more chromosomes involved [OR 1.76, 95% CI (1.23, 2.52); OR 1.86, 95% CI (1.25,2.78)]. Chr. 7, Chr. 2, Chr. 1, Chr. 18, Chr. 11, Chr. X, Chr. 13, Chr. 14, Chr. 12, and Chr. 9 were considered as prioritized chromosomes of mosaic embryos for transfer.
    This analysis support the embryos with mosaicism level ≥ 50%, whole chromosome(s) involved, multiple mosaic abnormalities were associated with worse pregnancy outcomes. Mosaicism level of 50% could be used as a threshold to assess the mosaic embryos.
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  • 文章类型: Journal Article
    BACKGROUND: Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial. Oocyte donation (OD) is often utilized to minimize maternal age effects on oocyte and embryo aneuploidy, thus providing an optimal model to assess the effect of PA. Several studies have revealed a higher than expected rate of aneuploidy in embryos derived from young oocyte donors, which warrants examination as to whether this may be attributed to advanced PA (APA).
    UNASSIGNED: The objective of this systematic review and individual patient data (IPD) meta-analysis is to evaluate existing evidence regarding an association between PA and chromosomal aberrations in an OD model.
    METHODS: This review was conducted according to PRISMA guidelines for systematic reviews and meta-analyses. Medline, Embase and Cochrane databases were searched from inception through March 2020 using the (MeSH) terms: chromosome aberrations, preimplantation genetic screening and IVF. Original research articles, reporting on the types and/or frequency of chromosomal aberrations in embryos derived from donor oocytes, including data regarding PA, were included. Studies reporting results of IVF cycles using only autologous oocytes were excluded. Quality appraisal of included studies was conducted independently by two reviewers using a modified Newcastle-Ottawa Assessment Scale. A one-stage IPD meta-analysis was performed to evaluate whether an association exists between PA and aneuploidy. Meta-analysis was performed using a generalized linear mixed model to account for clustering of embryos within patients and clustering of patients within studies.
    RESULTS: The search identified 13 032 references, independently screened by 2 reviewers, yielding 6 studies encompassing a total of 2637 IVF-OD cycles (n = 20 024 embryos). Two \'low\' quality studies using FISH to screen 12 chromosomes on Day 3 embryos (n = 649) reported higher total aneuploidy rates and specifically higher rates of trisomy 21, 18 and 13 in men ≥50 years. One \'moderate\' and three \'high\' quality studies, which used 24-chromosome screening, found no association between PA and aneuploidy in Day 5/6 embryos (n = 12 559). The IPD meta-analysis, which included three \'high\' quality studies (n = 10 830 Day 5/6 embryos), found no significant effect of PA on the rate of aneuploidy (odds ratio (OR) 0.97 per decade of age, 95% CI 0.91-1.03), which was robust to sensitivity analyses. There was no association between PA and individual chromosome aneuploidy or segmental aberrations, including for chromosomes X and Y (OR 1.06 per decade of age, 95% CI 0.92-1.21). Monosomy was most frequent for chromosome 16 (217/10802, 2.01%, 95% CI 1.76-2.29%) and trisomy was also most frequent for chromosome 16 (194/10802, 1.80%, 95% CI 1.56-2.06%).
    UNASSIGNED: We conclude, based on the available evidence, that APA is not associated with higher rates of aneuploidy in embryos derived from OD. These results will help fertility practitioners when providing preconception counselling, particularly to older men who desire to have a child.
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  • 文章类型: Journal Article
    背景:最近,日本妇产科学会发起了一项非整倍体植入前遗传学试验的临床研究.日本将非常需要标准化的胚胎活检技术。然而,金标准滋养外胚层(TE)活检程序尚未建立,这篇综述概述了TE活检的临床应用。
    方法:基于文献,TE活检的方法和相关技术,从胚泡中解剖TE细胞的方法,被调查了。
    结果:使用了两种TE活检方法,即辅助孵化(疝)和非辅助孵化(直接抽吸);然而,尚不清楚这些方法中哪一种更优越。了解轻弹或拉动方法是否有益是至关重要的。
    结论:非辅助孵化活检方法可能导致胚泡塌陷的可能性更高,可能会延长活检时间.活检程序应在3分钟内进行,因此直接TE抽吸可能具有更大的缺点。用激光脉冲进行TE解剖的牵引方法很简单。但是,过多的激光射击可能会导致更高的镶嵌频率。重要的是要了解TE活检的每种技术都有利弊。
    BACKGROUND: Recently, the Japan Society of Obstetrics and Gynecology initiated a clinical study of preimplantation genetic test for aneuploidy. There will be a great need for a standardized embryo biopsy technique in Japan. However, the gold standard trophectoderm (TE) biopsy procedure has not been established, and this review outlines the clinical use of TE biopsy.
    METHODS: Based on literature, the method and associated techniques for TE biopsy, a dissection method of TE cells from blastocysts, were investigated.
    RESULTS: Two TE biopsy methods are used, namely assisted hatching (herniating) and non-assisted hatching (direct suction); however, it is not clear which of these methods is superior. It is critical to understand whether the flicking or pulling method is beneficial.
    CONCLUSIONS: Non-assisted hatching biopsy method may cause blastocyst collapse with a higher probability, and it may extend the biopsy time. The biopsy procedure should be performed within 3 minutes, and thus direct TE suction may have greater disadvantages. It is a fact that pulling method of TE dissection with laser pulse is simple; however, excess laser shots may induce a higher frequency of mosaicism. It is important to understand that each technique of TE biopsy has benefits and disadvantages.
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  • 文章类型: Journal Article
    非整倍体概念构成了高龄产妇的大多数妊娠失败。对抗与年龄相关的生育能力下降的最佳方法是通过非整倍性的植入前遗传测试(PGT-A)。PGT-A允许更好的胚胎选择,这提高了单胚胎移植的着床率并降低了流产率。单胚胎移植可减少多胎妊娠和不良妊娠结局,如早产或低出生体重儿。延长胚胎培养的进展,胚泡活检技术,和24染色体非整倍体筛查平台使得PGT-A对于所有接受体外受精的患者都是安全和可获得的.提高新测序平台的基因组覆盖率,比如下一代测序,增加了植入前胚胎中镶嵌性和部分非整倍体的识别和诊断。移植时,与整倍体胚胎相比,马赛克胚胎的生存力降低,但是一些马赛克胚胎导致正常的活产。全基因组扩增伪影可能导致镶嵌症的误诊,或者一些镶嵌胚胎可能在植入后自我校正为整倍体。出于这个原因,没有整倍体胚胎的患者应在遗传咨询后选择移植马赛克胚胎。需要进一步的研究来表征哪些镶嵌胚胎可能是可行的。
    Aneuploid conceptions constitute the majority of pregnancy failures in women of advanced maternal age. The best way to combat age-related decline in fertility is through preimplantation genetic testing for aneuploidy (PGT-A). PGT-A allows for better embryo selection, which improves implantation rates with single embryo transfer and reduces miscarriage rates. Single embryo transfers decrease multiple gestations and adverse pregnancy outcomes such as preterm or low birth weight infants. Advancements in extended embryo culture, blastocyst biopsy techniques, and 24-chromosome aneuploidy screening platforms have made PGT-A safe and accessible for all patients who undergo in vitro fertilization. Improved genomic coverage of new sequencing platforms, such as next-generation sequencing, has increased the identification and diagnosis of mosaicism and partial aneuploidies in preimplantation embryos. Mosaic embryos have decreased viability compared to euploid embryos when transferred, but some mosaic embryos result in normal live births. Whole genome amplification artifacts may contribute to a misdiagnosis of mosaicism, or some mosaic embryos may self-correct to euploid after implantation. For this reason, patients without euploid embryos should be given the option of transferring mosaic embryos after genetic counseling. Further research is needed to characterize which mosaic embryos may be viable.
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