Non-invasive prenatal testing: impact on invasive prenatal diagnosis at a mainland Chinese tertiary medical center

Objective: We describe the changes over a 4-year period in the number of diagnostic testing after the introduction of non-invasive prenatal testing (NIPT).

Methods: The rate of NIPT as an indication in women who received amniocentesis, and the number of amniocentesis required for detection of one case with major aneuploidy were compared between a 1-year baseline period before the introduction of NIPT, and the 3 years following NIPT introduction.

Results: A total of 7536 amniocentesis procedures were performed over the 4-year study period. During the baseline period of the year 2011, the number of invasive testing required for detection of one common trisomy was 57. During the first 2 years that NIPT was offered, NIPT averaged 1.7 percent of the total indications for amniocentesis, and the required number of invasive testing decreased to 30. With the increase of the percentage of NIPT during the 3rd year, the required number of invasive testing further decreased to 26.

Conclusion: After the clinical introduction of NIPT, invasive prenatal diagnostic testing had not decreased at a Chinese prenatal diagnostic unit, but a remarkably improved detection rate of major aneuploidies in diagnostic procedures was observed.     

Cell-free DNA testing after combined test: factors affecting the uptake

Objective: First, to assess what was the uptake of cell free DNA (cfDNA) testing after a combined test and the maternal and fetal factors that influenced this decision, and second, to assess the uptake and factors that influence the choice of invasive testing.

Methods: This observational retrospective study included 1083 singleton pregnancies who had a combined test for screening for Down syndrome between 11?⁺?⁰ and 13?⁺?⁶ weeks. Multivariate logistic regression analysis was used to determine which factors affected the uptake of cfDNA test and invasive testing among risk for trisomies 21, 18, and 13, maternal characteristics and fetal nuchal translucency (NT) thickness.

Results: Two-hundred fifty-seven (23.7%) women had a cfDNA test, 89 (8.2%) had an invasive test, and 737 (68.1%) had no further test. The uptake of cfDNA increased with the risk for trisomies (p?<?0.001), maternal age (p?=?0.013), and was higher in nulliparous women (p?=?0.004). The uptake of invasive test increased with the risk for trisomies (p?<?0.001) and NT thickness (p?<?0.001).

Conclusions: This study shows that the uptake of cfDNA testing increases with the risk for trisomies, maternal age, and is higher in nulliparous, whereas the uptake of invasive testing increases with the risk for trisomies and NT thickness.     

Comprehensive assessment of a clinic's experience of preimplantation genetic testing by a cumulative rate

ObjectiveThis study aimed to investigate the outcomes of patients who had preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) or for aneuploidy screening (PGT-A) with different indications.MethodsThis was a retrospective study at a single center. Pregnancy outcomes of all couples who had PGT from 2014 to 2018 were retrospectively analyzed, and the cumulative pregnancy rates (CPR) and the cumulative live birth/ongoing pregnancy rate (CLB/OPR) per patient with at least one transfer cycle were calculated.ResultsA total of 313 PGT-SR cycles of 255 patients, 22 PGT-sexing cycles of 20 patients, and 190 PGT-A cycles of 168 patients were performed during the period. In PGT-SR, the overall CPR and the CLB/OPR were 68.04% and 59.79%, respectively. In PGT-A, the CPR and CLB/OPR were 67.52% and 58.12%, respectively. We also found that the CPR (93.75%) and CLB/OPR (87.50%) were highest in patients for PGT-sexing with a diagnosis of Y chromosomal microdeletion. In addition, we discovered a significant trend that aneuploidy rate significantly increased with maternal age (p = 0.000) in PGT-A population. No significant difference was found in the mosaicism rate or clinical outcomes among the age groups. Similarly, the significance was absent in the PGT-SR population.ConclusionWe reviewed the CPR and CLB/OPR for different indications since the 24-chromosome technique has been applied in the clinical setting for 4 years in our center. We hope that our results will provide some pointed guidance and a new perspective on outcomes for PGT in certain patients and clinicians.     

Cytogenetic testing of anembryonic pregnancies compared to embryonic missed abortions

Purpose The objective of this study is to determine the rate of abnormalities detected by cytogenetic testing of first trimester miscarriages, in patients with and without an embryonic pole seen on ultrasound. Materials and methods A retrospective study of 272 D&Cs for missed abortions in an academic infertility practice from 1999 to 2006. Karyotype results were compared with transvaginal ultrasound findings. Chi-squared analysis was used with a P < 0.05 for significance. Results There was a high rate of abnormal karyotypes in all miscarriages (65%). Rates of abnormal karyotypes were 58% and 68% in cases with anembryonic gestations and those with a fetal pole seen, respectively (P > 0.05). Conclusion The high rate of abnormalities detected in both groups suggests that useful results can be obtained from chromosomal testing of the POC regardless of ultrasound findings. Further studies on the prognostic value and cost effectiveness of chromosomal testing are needed.     

染色体易位携带者胚胎植入前遗传学诊断进展

染色体易位携带者通常无明显表型异常,但却存在生育问题,可发生流产、死产、胎儿畸形及新生儿智力低下。主要原因是在受精卵形成过程中产生非平衡易位胚胎,伴随染色体片段的重复及缺失。染色体易位携带者可通过辅助生殖技术及胚胎植入前遗传学诊断技术鉴别非平衡易位胚胎,将筛选出的正常或平衡易位胚胎进行宫腔内植入,从而避免不良孕产史的发生。介绍染色体易位的概念、分类、发生不良孕产史的机制、相互易位及罗伯逊易位理论上获得正常胚胎的概率,阐述胚胎植入前诊断技术的适应证,综述目前常用的胚胎植入前遗传学诊断技术,包括荧光原位杂交技术（FISH）、光谱核型分析技术（SKY）、比较基因组杂交（CGH）技术、微阵列-比较基因组杂交（aCGH）、单核苷酸多态性（SNP）及新一代测序（NGS）技术的原理、分类、检测范围、优点及局限性,以及这些技术在染色体易位携带者胚胎植入前遗传学诊断中的价值。     

氯化汞对雄性果蝇生殖细胞非整倍体的影响

应用黑腹果蝇Ｘ或Ｙ染色体丢失试验研究了氯化汞对雄性果蝇生殖细胞染色体的损伤。结果表明，染毒浓度为０．１％及０．２％的氯化汞组染色体丢失率均为０．０４％，与阴性对照组的染色体丢失率用Ｋａｓｔｅｎｂａｕｍ－Ｂｏｗｍａｎ表检验，差异无显著性，即氯化汞对雄性果蝇生殖细胞的染色体无损伤作用，此结果可能由于所用雄蝇品系不够敏感所致。     

胃癌端粒酶活性与DNA倍体的关系及临床意义

目的：探讨胃癌组织中端粒酶活性与DNA倍体的关系及临床意义。方法：用端粒酶重复序列扩增法（TRAP）检测胃癌组织中的端粒酶活性,用DNA图像分析仪（ICM）检测肿瘤细胞核DNA倍体。结果：胃癌组织中端粒酶的阳性表达率为81．25％,早期胃癌病例的阳性率为55．5％,进展期胃癌的阳性率87．2％。48例中异倍体肿瘤33例,占68．7％。33例异倍体胃癌中91％（30／33）显示端粒酶活性。结论：胃癌组织中端粒酶活性与DNA异倍体率有明显的相关性,端粒酶的表达与胃癌的病程进展有关。     

血清学结合超声检查在非整倍体产前筛查中的应用

目的:探讨血清学结合超声在胎儿非整倍体产前筛查中的应用价值。方法:采用孕中期孕母血清学三联(AFP、Freeβ-hCG、uE3)检测结合胎儿系统超声检查,对1 831例孕16~25周孕妇进行胎儿非整倍体染色体病产前筛查,对筛查高风险孕妇,进行羊水细胞染色体核型分析。结果:1 831例孕妇中筛查出高危孕妇107例,其中血清学筛查高危孕妇98例,超声检查胎儿异常9例,经羊水细胞染色体分析产前诊断确诊唐氏综合征2例、18-三体综合征2例。结论:孕中期血清三联筛查结合胎儿系统超声检查的产前筛查方案,可扩大筛查目标的涵盖范围,减少漏诊及误诊,有效提高胎儿非整倍体染色体异常的检出率,是一种简单、无创、有效的产前筛查模式。     

425例羊水染色体核型分析与荧光原位杂交方法的比较

目的比较425例羊水染色体核型分析与染色体13,18,21,X和Y荧光原位杂交方法的结果,评估染色体13,18,21,X和Y荧光原位杂交作为染色体异常独立测试的安全性并分析漏诊染色体异常的类别。方法以染色体核型分析作为金标准,比较了2011年3-7月425例患者的羊水染色体核型分析与荧光原位杂交方法的结果。结果在425例患者中染色体核型分析共发现22例染色体异常（包括16例非整倍体）。染色体异常率为5.2%（22/425）,非整倍体率为72.7%（16/22）。染色体13,18,21,X和Y荧光原位杂交方法共发现15例染色体异常,漏诊一例嵌合体。针对染色体13,18,21,X和Y,荧光原位杂交的敏感性和特异性分别为93.75%和100%,针对全部染色体时,荧光原位杂交的敏感性降到了68.2%而特异性仍为100%。荧光原位杂交漏诊的7例染色体异常分别为3例染色体易位,3例染色体到位,1例嵌合体。结论本研究不支持荧光原位杂交作为检测染色体异常的独立测试。