目的:评估产前无细胞DNA筛查染色体非整倍体的阳性预测值(PPV),无论是在IVF/PGT周期中的单个整倍体移植还是单个未测试胚胎移植后,并评估产前cfDNA筛查和PGT-A结果的一致性。
方法:单中心回顾性队列研究主题:最常见三体(T)的2973例产前cfDNA筛查结果(T13,T18,T21,X,Y)和微缺失(1p36;4p16.3;5p15.2;15q11.2;22q11.2)来自单胎妊娠,分为两组:PGT-A组(n=1204)单个整倍体移植后的妊娠和非PGT-A组(n=1769)单个未测试胚胎移植后的妊娠,2016年至2023年。
方法:主要结局指标是产前无细胞DNA筛查的准确性。产前无细胞DNA筛查结果阳性和阴性,随后的产前或产后诊断测试用于将每个阳性的产前无细胞DNA筛查结果分类为真阳性或假阳性.次要终点是评估PGT-A和产前无细胞DNA筛查结果的一致性,并评估用于产前无细胞DNA筛查报告的无细胞DNA胎儿分数的差异研究组之间。
结果:产前无细胞DNA筛查在平均11.3±1.8周孕龄(GA)进行,并在99.9%的患者中获得了结果(取消率0.1%)。PGT-A测试和未测试的妊娠之间的胎儿分数没有差异(9.5%±4%vs10.3%±4%)。13阳性产前无细胞DNA筛查结果(2-T21,2-X0,4-XXX,1-XYY,1-不确定的性别,2-22q11del/dup,PGT-A组收到1-15q11.2)。羊膜穿刺术和胎儿尸检仅证实1例(22q11dup),给予7.7%的异常产前cfDNA筛查的PPV,其余的结果与PGT-A一致。产前无细胞DNA筛查和PGT-A结果之间的性染色体是100%一致的,对于性染色体,PGT-A给予100%PPV,非整倍体给予100%NPV。产前无细胞DNA筛查阳性结果来自未测试胚胎的27例妊娠(1.5%),对21人进行了选择性的随访测试,其中8人确认了产前无细胞DNA筛查结果,给予非PGT-A组38%的PPV。
结论:这项研究表明,接受IVF/PGT和单整倍体胚胎移植的患者在孕早期可以可靠地进行产前无细胞DNA筛查。PGT-A测试胚胎后的单胎妊娠中的胎儿分数与未测试胚胎的妊娠没有区别。整倍体胚胎移植后异常的产前无细胞DNA筛查结果的PPV低得令人放心(7.7%)。PGT-A可靠地选择与胎儿性别100%一致的非整倍体。
OBJECTIVE: To evaluate the positive predictive value (PPV) of prenatal cell-free DNA screening for chromosomal aneuploidies in pregnancies achieved either after single euploid transfer in IVF/PGT cycles or transfer of single untested embryo, and to assess the concordance of prenatal-cfDNA-screening and PGT-A results.
METHODS: Single centre retrospective cohort study SUBJECTS: 2973 prenatal-cfDNA-screening results for the most common trisomies(T)(T13,T18,T21,X,Y) and microdeletions(1p36;4p16.3;5p15.2;15q11.2;22q11.2) from singleton pregnancies allocated into 2 groups: PGT-A group (n=1204) pregnancy after single euploid transfer and non-PGT-A group (n=1769) pregnancy after transfer of single untested embryo, between 2016 and 2023.
METHODS: Primary outcome measure was accuracy of prenatal-cell-free-DNA-screening. Positive and negative prenatal-cell-free-DNA-screening results, and subsequent prenatal or postnatal diagnostic testing were used to classify each positive prenatal-cell-free-DNA-screening result as a true or a false positive. Secondary endpoints were to evaluate the concordance of PGT-A and prenatal-cell-free-DNA-screening results and to assess the differences of the fetal fraction of cell-free-DNA used for prenatal-cell-free-DNA-screening report between the study groups.
RESULTS: Prenatal-cell-free-DNA-screening was performed at mean 11.3±1.8weeks gestational age (GA) and yielded results in 99.9% of the patients (0.1% cancellation rate). There was no difference in the fetal fraction between PGT-A tested and not tested pregnancies (9.5%±4% vs 10.3%±4%). 13 positive prenatal-cell-free-DNA-screening results (2-T21,2-X0,4-XXX,1-XYY, 1-indeterminate sex, 2-22q11 del/dup, 1-15q11.2) were received for PGT-A group. Only one (22q11 dup) was confirmed with amniocentesis and fetal autopsy, giving a PPV for an abnormal prenatal-cfDNA-screening of 7.7%, the rest had results concordant with PGT-A. Sex chromosomes were 100% concordant between prenatal-cell-free-DNA-screening and PGT-A results, giving a 100% PPV for PGT-A for sex chromosomes and 100% NPV for aneuploidies. Positive prenatal-cell-free-DNA-screening results were received for 27 pregnancies from untested embryos (1.5%), follow up testing was electively performed for 21, and 8 had confirmed the prenatal-cell-free-DNA-screening result, giving a PPV for the non-PGT-A group of 38%.
CONCLUSIONS: This study demonstrates that patients undergoing IVF/PGT and single euploid embryo transfer can reliably do prenatal-cell-free-DNA-screening during their first trimester. Fetal fraction in singleton pregnancies after PGT-A tested embryos is not different from pregnancies with untested embryos. PPV for an abnormal prenatal-cell-free-DNA-screening result after euploid embryo transfer was reassuringly low (7.7%). PGT-A reliably selects against aneuploidy with 100% concordance with fetal sex.