Clinical Performance of Cell-Free Fetal DNA Testing for Fetal Aneuploidies and Subchromosomal Deletions/Duplications in a Cohort of 19,531 Pregnancies

Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.

Fibrinogen to be a laboratory screening biomarker for polycystic ovary syndrome(PCOS) patients:a Meta-analysis

Objective To assess the fibrinogen levels in polycystic ovary syndrome （PCOS） patients and to fgure out the potential of fibrinogen to be an early phase laboratory biomarker for PCOS diagnosis. Methods A systemic literature research was performed from databases of Medline via OVID, PubMed, Web of Knowledge and the Cochrane library databases, etc. Fifteen studies including 694 PCOS patients and 548 normal controls were selected after quality assessment. Data of fibrinogen levels, age and body weight were extracted and analyzed systemically. Results Fibrinogen increases in PCOS patients with regard to data poolings of overall studies （mean difference=21.51, 95%CI=3.78-39.25, P=0.02）, National Institutes of Health （NIH）-based studies （mean difference=8. 50, 95%CI=0.91-16. 09, P= 0. 03） and Rotterdam-based studies （mean difference=45.61, 95%CI=12.18-79.03, P=0.007） respectively. PCOS patients are younger （mean difference= -2.15, 95%CI= -3.65 - -0. 64, P=0. 005） and with heavier body weight （mean difference=0.92, 95%CI=0.59- 1.25, P〈0.001） than normal controls. Conclusions Increasing in PCOS patients, fibrinogen might be used as a diagnosis biomarker for PCOS, especially in the population with younger age and heavier body weight, which indicates that fibrinogen might be used as an early phase laboratory screening biomarker in clinical practice.

The imbalance of T-cell immunoglobulin and ITIM domain and CD226 on regulatory T cell in recurrent spontaneous abortion patients

Objective:To analyze the proportion of peripheral regulatory T cells(Tregs)and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain(TIGIT)and CD226 on Tregs in patients with recurrent spontaneous abortion(RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group(4.41%±1.54%)was significantly lower than that in the control group(5.27%±1.52%,P=0.0374).Compared with the normal pregnant women,patients with RSA showed decreased TIGIT expression(54.75±9.70%vs.63.07±12.48%,P=0.0066)and increased CD226 expression on Tregs(25.59%±8.22%vs.20.46%±6.97%,P=0.0168).The ratio of CD226 to TIGIT in the RSA group(0.48±0.19)was higher than that in the control group(0.34±0.15,P=0.0027).The proportion of TIGIT+CD226+Tregs was significantly lower in patients with RSA(9.30%±4.95%vs.13.43%±4.72%,P=0.0020)than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.