Normal Fetal Karyotype Research Articles

Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21.

In this study, we compared the ratio of second trimester fetal biometric measurements to nasal bone length (NBL) in fetuses with normal karyotype and trisomy 21 to determine their diagnostic prognostic value. The study included 148 pregnant women who obtained second-trimester ultrasonographic fetal anatomy and had amniocentesis (AS) for fetal karyotyping. The fetal karyotype results divided the groups into normal and trisomy 21 fetuses. Age, obstetric history, first and/or second trimester screening test risk ratios, fetal biometric measurements, and NBL mm, median (MoM) multiples, and percentile values were recorded and compared between groups. BPD/NBL ratios above 9.26 predict trisomy 21 in fetuses with 77.6% sensitivity and 86.1% specificity (p = 0.001). HC/NBL ratios above 34.50 predict trisomy 21 in fetuses with 77.8% sensitivity and 88.8% specificity (p = 0.001). FL/NBL ratios above 6.02 predict trisomy 21 in fetuses with 69.6% sensitivity and 72.2% specificity (p = 0.001). HL/NB ratios above 6.56 predict trisomy 21 in fetuses with 95.5% sensitivity and 47.2% specificity (p = 0.001). The NBL MoM value demonstrated a high diagnostic accuracy for normal-karyotype fetuses (p = 0.021). We found that BPD/NBL, HC/NBL, FL/NBL, and HL/NBL ratios differed between fetuses with a normal karyotype and those with trisomy 21, specifically the HC/NBL ratio, which predicted trisomy 21 with good diagnostic accuracy. In identifying normal-karyotype fetuses, the NBL MoM was highly accurate.

#46 : Outcomes of Transfer Abnormally Chromosomal Embryos

Background and Aims: In some couples, there was no normal chromosomal embryos after preimplantation genetic testing (PGT) for aneuploidy (PGT-A), for structural chromosomal rearrangements (PGT-SR) or for monogenic (PGT-M). The couples decided to use the abnormal embryos for transfer after thorough genetic counselling. This study reports the outcomes of transfer abnormally chromosomal embryos. Method: This retrospective study was conducted from January 2020 to December 2022 at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. The abnormally chromosomal embryos that were considered for transfer included aneuploidy related to [Formula: see text]3 chromosomes (except trisomy 13, 18, 21 and monosomy X); or mosaicism has [Formula: see text]50% of aneuploidy after PGT-A, PGT-SR or PGT-M (except mosaic trisomy 13, 18, 21 and monosomy X). Results: 94 patients transferred 94 single abnormally chromosomal embryos. Out of 94 embryos, 62 were mosaic and 32 were aneuploid. Among the group of mosaic embryos, 25 (40.3%) had segmental, 32 (51.6%) had 1 or 2 chromosomal abnormalities and 5 (8.1%) had 3 or more. Among the group of aneuploid embryos, 4 (12.5%) had segmental, 13 (40.6%) had 1 chomosomal abnormalities, 5 (15.6%) had 2 chomosomal abnormalities and 10 (31.3%) complexes (both mosaic and aneuploid chromosome). Among 20 live births, 2 cases have normal fetal karyotype, and 11 cases have normal CNVs blood results. Conclusion: Mosaic embryos can be considered for transfer in cases having no normal embryos after PGT. More than 50% of babies born from chromosomally abnormal embryo transfer have normal chromosomal results.

Pregnancy outcomes of normal karyotype fetuses with increased nuchal translucency.

Although the association between first-trimester increased nuchal translucency (NT) and chromosomal defects is well-defined, there is little knowledge about the importance of increased NT in fetuses with normal karyotypes. Hence, this study was designed to evaluate outcomes of normal karyotype fetuses with increased NT. This observational retrospective study was conducted on 720 pregnancies with increased NT (>3mm) at 11 to 13 weeks of gestational age in Yas Hospital, Tehran, Iran, from 2016 to 2020. Study outcomes were incidence of preeclampsia, intrauterine growth restriction) IUGR (, preterm labor, fetal anomaly, cardiac malformations, hydrops fetalis, abortion, and intrauterine fetal death (IUFD) in pregnancies without evident chromosomal karyotype abnormalities. Out of 720 participants who underwent karyotyping in the study center, 523 fetuses had normal karyotype results. In the pregnancies assessed for outcome, 357 (68.3%) reached live birth, 104 (19.9%) aborted, and 62 (11.9%) resulted in IUFD. Study outcomes including preeclampsia (<0.001), IUGR (<0.001), preterm labor (<0.001), fetal anomaly (<0.001), cardiac malformations (<0.001), hydrops fetalis (0.017), abortion (<0.001), and IUFD (<0.001) resulted in a statistically significant difference in the distribution of cases across NT intervals. This study demonstrated adverse pregnancy outcomes increased with increasing NT despite normal karyotyping. Hence, tight observation of mothers and fetuses should be done in normal karyotype fetuses with increased NT.

Serum biochemical parameters in pregnant women with and without fetal chromosomal abnornalities

Aim. To analyse the levels of serum beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women without fetal chromosomal abnormalities and with fetal trisomy 21 (Down syndrome) or 18 (Edwards syndrome).Materials and Methods. We performed a retrospective analysis of serum biochemical parameters of 1214 women who had previously undergone karyotyping as a part of prenatal or postnatal screening. Patients were stratified into those with a normal fetal karyotype, those carrying a fetus with trisomy 21, and those carrying a fetus with trisomy 18. Levels of serum β-hCG and PAPP-A were estimated using the AutoDELFIA automatic immunoassay system.Results. In most of the women carrying a fetus with trisomy 21, serum β-hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b -hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b-hCG and PAPP-A are sensitive markers of fetal trisomy 21 and trisomy 18 in pregnant women.

P-398 HLA expression profile - the picture of successful pregnancy

Abstract Study question Which the difference of HLA profile expression among normal and abnormal karyotype? Summary answer In missed abortion groups, a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with normal karyotype group. What is known already The study of pregnant alloimmunity confirms the relationship of recurrent miscarriage with the individual characteristics of the HLA I and II class system (Human leukocyte antigen), which can lead to impaired production of the mixed lymphocyte reaction blocking antibodies (MLR-Bf), anti-paternalcyto-toxicantibodies (APCA) and anti-idiotypic antibodies, Ab2, which are necessary for successful implantation and pregnancy development. For example, HLA-G is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, to placenta, amnion when HLA II class system mostly determinates in dNK, T-cells, macrophages. Study design, size, duration It was a prospective complex cohort study from 2016-2020 years with cytogenetics and pathomorphological investigations. The purpose of this study is to investigate HLA-DR expression in gravid endometrium, HLA-G and KIR2DL4 expression in chorionic villous among 3 groups (study included 115 cases of abortion material): group 1 – 36 cases after missed abortion with normal karyotype, group 2–35 cases after missed abortion with polyploidy and group 3–44 cases after induced abortion group (normal pregnancy). Participants/materials, setting, methods Criteria of inclusion: abortive material from 3 groups of women with missed or after induced abortion; 6-12 weeks, singleton pregnancy, cytogenetic of chorionic villous was obligatorily - normal fetal karyotype and polyploidy of fetus. In this work, we used: cytogenetic method and morphological study (histological-H&amp;E stain, immunohistochemical, morphometric method). Immunohistochemical examination included quantitative and qualitative assessment of the expression of Anti-HLA-DR (mouse monoclonal), Anti-HLA-G (mouse monoclonal) and AntiKIR2DL1+KIR2DL3 + KIR2DL4 + KIR2DS4 (rabbit polyclonal). Main results and the role of chance By IHC the expression of HLA-G in extravillous trophoblast cells but the expression of HLA-DR and KIR2DL4 were detected in stroma, glands, the endometrial epithelium, both in groups.The HLA-G expression area in both groups with missed abortion didn’t differ statistically. But the expression of HLA-G in 3 group was strictly higher (in group 1 with a normal karyotype 37.7, in group 2-36.4, in the control group 67.09, p &amp;lt; 0.001). When divided into subgroups depending on the karyotype, the following data were obtained: in the group with a non-developing pregnancy with a normal karyotype of male fetuses, there is a tendency to lower expression of HLA-G molecules compared to female fetuses (32.96 (10.22) and 41 .45(9.36), respectively). Expression of the KIR2DL4 receptor was verified in chorionic villi (in the cytotrophoblast and syncytiotrophoblast), as well as in the structures of the endometrium, both in the glands, stroma, and in the surface epithelium, regardless of the karyotype. The expression area of the KIR2DL4 receptor did not differ statistically between the three groups (29.6, 33.1 and 27.55, p = 0.75). The expression area of the HLA-DR was detected in each group in gravid endometrium, but it hadn’t statistically differences (44.1, 38.2 and 42.5, p = 0.82). Limitations, reasons for caution No reasons for cautions Wider implications of the findings In missed abortion groups,a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with the control group.The mechanism of abortion in groups with missed abortion with both normal karyotype and pathological karyotype of the fetus is identical.HLA-G molecule has a leading role in successful implantation. Trial registration number АААА-А20-120041390025-9

Incidental Findings of Copy Number Variants by SNP-Based Noninvasive Prenatal Testing: Implications for Maternal Health

Somatic abnormalities involving chromosome 21, 18, and 13 are found in cancers and are detectable in circulating cfDNA. Previous publications have suggested increased risks of maternal neoplasm when multiple aneuploidies are detected on non-SNP-based NIPTs with normal fetal karyotypes. SNP-based NIPT distinguishes maternal/fetal cfDNA, allowing for CNV origin identification. This study reviewed maternal/fetal outcome SNP-based NIPT data to determine if multiple maternal copy number variants (CNVs) can predict increased risk of maternal neoplasms.

Analysis to the failure rate and causes of noninvasive prenatal testing based on high-throughput sequencing

To analyze the cause and pregnancy outcome for non-reportable cell-free DNA (cfDNA) results during non-invasive prenatal testing (NIPT). cfDNA was extracted from maternal plasma from 5898 singleton pregnancies at 12 to 22 gestational weeks and underwent NIPT with strict quality control standards. For those with sub-standard results, redraw or invasive prenatal procedures were recommended. Among the 5898 cases, 32 have failed for the initial NIPT, including 17 cases with substandard cffDNA%, 10 cases with data fluctuation after twice library constructing and sequencing, and 5 cases with unidentifiable sex chromosome abnormalities. For these 32 cases, 2 directly underwent amniocentesis, and karyotyping analysis showed both were normal. Six of the 30 redrawn cases finally turned out to be nonreportable. The final nonreportable rate was therefore 0.1% (8/5898). Of the redrawn cases, 1 trisomy 21, 1 trisomy 18 and 1 trisomy 13 high risk-cases were identified, which were all confirmed to be false positive. Among the 6 nonreportable cases, 2 women underwent invasive prenatal testing, and 1 was found to have a normal fetal karyotype, while another was found to have an abnormal karyotype of mos45,X[32]/46,XY[18]. The other 4 nonreportable cases who did not accept invasive prenatal testing have all reported normal child development at follow-up. The main reason for nonreportable NIPT results was low cffDNA%. The high success rate of the redrawn cases has effectively increased the overall NIPT success rate and reduced the number of the cases necessitating invasive prenatal diagnosis. The initially nonreportable women may consider retesting after careful counseling with informed consent.

Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (

The present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff < 4% were matched with a control group with normal levels of cfDNAff > 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.

P–414 HLA-G expression as a new prognostic marker of successful implantation

Abstract Study question Is the low HLA-G expression a determinant of early reproductive loss? Summary answer Low expression of HLA-G is associated with pregnancy complications and can be one of the reasons of spontaneous abortion (such as RPL). What is known already The dysregulated maternal immune responses to invading embryos may play role in RIF, RPL, and second- and third-trimester obstetrical conditions. HLA-G is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother, thus critically contributing to fetal–maternal tolerance due to inducing displacement of pro-inflammatory to Th1 cell-mediated response of Th2, has a positive influence on the process of implantation. HLA-G is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, to placenta, amnion. Study design, size, duration It was a prospective complex cohort study from 2016–2020 years with pathomorphological investigations. The purpose of this study is to investigate the HLA-G and KIR2DL4 expression in chorionic villous among 3 groups (study included 118 cases of abortion material): group 1 – 36 cases after missed abortion with normal karyotype, group 2 – 36 cases after missed abortion with polyploidy and group 3 – 46 cases after induced abortion group (normal pregnancy). Participants/materials, setting, methods Criteria of inclusion: abortive material from 3 groups of women with missed or after induced abortion; 6–12 weeks, singleton pregnancy, cytogenetic of chorionic villous was obligatorily - normal fetal karyotype and polyploidy of fetus. Pathomorophological investigation included H&amp;E stain, IHC and confocal laser scanning microscopy. Immunohistochemical examination included quantitative and qualitative assessment of the expression of Anti-HLA-G (mouse monoclonal) in an extra villous trophoblast and Anti-KIR2DL1+KIR2DL3 + KIR2DL4 + KIR2DS4 (rabbit polyclonal) in chorionic villi. Main results and the role of chance The immunohistochemical study showed homogenous distribution HLA-G expression in extravillous trophoblast cells (EVT) and KIR2DL4 expression in chorion villous both in missed abortion groups and in induced abortion group. HLA-G expression average relative area in 1 and 2 groups was not statistically different (in 1 group with normal karyotype 33,9±3,5 and in 2 group 38,6±2,8). But the expression of HLA-G in 3 group was strictly higher (55,6 ±2,4). The average relative area of KIR2DL4 receptor wasn’t statistically different among 3 groups. However, the histological picture both missed abortion groups (for the genetic\immunological reasons for rejection) is the only one - this is a missed abortion of an early terms of gestation. In a histological study of missed abortion, as our study shows, the histological picture is similar in 1 and 2 groups. Thus, in 1 group with a normal karyotype of the fetus (before conducting the chorion cytogenetic study in the genetics laboratory) in 59.2% the histological examination determined a picture of an impaired early pregnancy with signs of trophoblast chromosomal pathology. Thus, without a cytogenetic study of the chorion, it is impossible to clearly determine whether the chromosomal pathology of the fetus is the cause of missed abortion. Limitations, reasons for caution There is no limitations, reasons for caution. Wider implications of the findings: Thus, HLA-G molecule has a leading role in the onset and successful prolongation of pregnancy, implantation, placentation and fetal development. Trial registration number 98–2019

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of β-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. PAPP-A and β-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and β-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and β-hCG MoM 0.2-0.5 range. Maternal free β-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal β-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and β-hCG MoMs, fetal NT measurement was an requirment.

Clinical Significance of Non-Invasive Prenatal Screening for Trisomy 7: Cohort Study and Literature Review.

Trisomy 7 is the most frequently observed type of rare autosomal trisomies in genome-wide non-invasive prenatal screening (NIPS). Currently, the clinical significance of trisomy 7 NIPS-positive results is still unknown. We reviewed two independent cohorts from two laboratories where similar NIPS metrics were applied. A total of 70,441 singleton cases who underwent genome-wide NIPS were analyzed, among which 39 pregnancies were positive for trisomy 7, yielding a screen-positive rate of 0.055% (39/70,441). There were 28 cases with invasive testing results available; the positive predictive value (PPV) was 3.6% (1/28). We then searched the published NIPS studies to generate a large cohort of 437,873 pregnancies and identified 247 cases (0.056%) that were screened positive for trisomy 7. The overall PPV was 3.4% (4/118) in the combined data. The presence of uniparental disomy 7 was not detected in the NIPS trisomy 7-positive pregnancies with normal fetal karyotype. Among the 85 cases with pregnancy outcome available in combined data, 88.2% were normal live births, 14.1% had intrauterine growth restriction, preterm birth or low birth weight, 3.5% presented with ultrasound abnormality, and no fetal loss was observed. Our data provide valuable information for counseling and management of trisomy 7-positive NIPS pregnancies.

Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion

Objective Human leukocyte antigen-G (HLA-G) is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother. HLA-G expression is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, placenta, amnion. Methods: The purpose of this study is to investigate the HLA-G and KIR2DL4 expression in chorionic villous among 2 groups with missed abortion: group 1 – 27cases with normal karyotype and group 2 – 22 with fetal polyploidy. Criteria of inclusion: abortive material from two groups of women with missed abortion; 6–12 weeks gestational age, singleton pregnancy, cytogenetic of chorionic villous was obligatory – normal fetal karyotype and polyploidy of fetus. Results: During IHC investigations the average relative area of HLA-G expression in trophoblast was counted (in 1st group 33.9 ± 3.5 and in 2nd group 38.6 ± 2.8). Expression of HLA-G the most verified in extravillous chorion stroma. The average relative area of KIR2DL4 receptor was not statistically different among two groups (31.6 ± 2.4 and 32.2 ± 1.7). Conclusions These results suggest the role of HLA-G for the progression in early reproductive losses. Low expression of HLA-G is associated with pregnancy complications and can be one of the reasons for spontaneous abortion.

Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes.

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6–8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2–3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.

The Mechanism of Prune Belly Syndrome Development: A Sonographic Sequential Assessment

Prune belly syndrome is a rare disorder characterized by the absence of anterior abdominal wall muscles, bilateral cryptorchidism, and urinary tract malformations. The aim of this case study was to illustrate the developmental sequelae of prune belly syndrome, acquired through a series of antenatal sonography. A 20-year-old woman visited a diagnostic medical sonography center for an obstetrical sonogram. Her fetus was diagnosed with megacystis at 15 weeks’ gestation. The mother returned for repeated appointment and to observe fetal changes during the development of prune belly syndrome. First, the megacystis, hydroureter, and hydronephrosis were noted followed by hazy ascitic and amniotic fluid. The hemodynamics were altered in the umbilical artery, middle cerebral artery, and ductus venosus. Subsequently, the pressure was neutralized, but it was observed after birth that the newborn had cryptorchidism, a distended abdomen with wrinkled wall, and absent right kidney. In conclusion, prune belly syndrome could be caused by megacystis due to bladder outlet obstruction in otherwise normal karyotype fetuses. Megacystis leads to hydroureter, hydronephrosis, and abdominal distention. The persistent abdominal distention gives rise to the underdevelopment of anterior abdominal wall muscles and cryptorchidism.

Euploid miscarriage is associated with elevated serum C-reactive protein levels in infertile women: a pilot study

PurposeIncreased serum C-protein (CRP) levels reduce fecundity in healthy eumenorrheic women with 1–2 pregnancy losses. Subclinical systemic inflammation may impede maternal immune tolerance toward the fetal semi-allograft, compromising implantation and early embryonic development. Some miscarriages with normal karyotypes could, therefore, be caused by inflammation. Whether pre-pregnancy CRP relates to karyotypes of spontaneously aborted products of conception (POCs) was investigated.MethodsA study cohort of 100 infertile women with missed abortions who underwent vacuum aspirations followed by cytogenetic analysis of their products of conception tissue was evaluated at an academically affiliated fertility center. Since a normal female fetus cannot be differentiated from maternal cell contamination (MCC) in conventional chromosomal analyses, POC testing was performed by chromosomal microarray analysis. MCC cases and incomplete data were excluded. Associations of elevated CRP with first trimester pregnancy loss in the presence of a normal fetal karyotype were investigated.ResultsMean patients’ age was 39.9 ± 5.8 years; they demonstrated a BMI of 23.9 ± 4.6 kg/m2 and antiMullerian hormone (AMH) of 1.7 ± 2.4 ng/mL; 21.3% were parous, 19.1% reported no prior pregnancy losses, 36.2% 1–2 and 6.4% ≥ 3 losses. Karyotypes were normal in 34% and abnormal in 66%. Adjusted for BMI, women with elevated CRP were more likely to experience euploid pregnancy loss (p = 0.03). This relationship persisted when controlled for female age and AMH.ConclusionsWomen with elevated CRP levels were more likely to experience first trimester miscarriage with normal fetal karyotype. This relationship suggests an association between subclinical inflammation and miscarriage.

The impact of invasive prenatal testing on anxiety and sleep quality in pregnant women with a screen-positive result for aneuploidy

Purpose Prenatal anxiety has negative effects on pregnancy and neonate. Both screening tests and invasive diagnostic tests are associated with elevated anxiety level. But a normal fetal karyotype result could improve the anxiety level in high-risk patients. We hypothesized that patients who prefer follow-up without karyotyping may experience increased anxiety and sleep impairment until delivery. Our aim was to determine the effect of invasive diagnostic test decision on anxiety and sleep quality in women with a positive screening result. Methods 132 women were included for the study and three groups were described. The invasive group consisted of women who underwent invasive procedure after a screen-positive test result, the follow-up group consisted of women who preferred non-invasive follow-up after a screen-positive result and the control group consisted of women with screen-negative test results. Participants were evaluated with the State-Trait Anxiety Inventory (STAI) and the Pittsburgh Sleep Quality Index (PSQI) after genetic counseling. They were asked for completing the same questionnaires in the third trimester to establish the course of anxiety and sleep quality throughout pregnancy. Results STAI scores were significantly higher in both screen-positive groups than in the control group in the first evaluation (p < 0.001). STAI scores decreased in the invasive group and controls while PSQI scores did not significantly change during the course of the pregnancy. However, the anxiety level and sleep quality were worsened over time in the follow-up group. Conclusion Screen-positive women who preferred to follow up had higher anxiety level and worse sleep quality in the later stages of pregnancy. We concluded that invasive prenatal diagnostic tests could improve anxiety and sleep quality in pregnant women with a screen-positive result for aneuploidy.

An Intelligent Prenatal Screening System for the Prediction of Trisomy-21 Using Triple Test Variables: The Hacettepe System

Objective: To introduce an intelligent prenatal screening system, using triple test variables.Study Design: In this study, we have used a backpropagation learning algorithm (a supervised artificial neural network) to develop an intelligent antenatal screening system (heretofore referred as Hacettepe System). Triple test variables were used as input variables, while “Down syndrome” and “non-Down syndrome” fetuses were the output of the algorithm. Unconjugated estriol (E3), beta-human chorionic gonadotropin, and α-feto protein with gestational week and maternal age (triple test) were used as input variables in the training and testing. Multiples of median values of the E3, α-feto protein, and beta-human chorionic gonadotropin were used in this study. The testing group of Hacettepe system consisted of 97 patients who were found to be high-risk (&gt;1/250) during the routine antenatal screening (triple test) and underwent amniocentesis for fetal karyotyping.Results: Amniocentesis was performed in 97 pregnancies with “high-risk” triple test results (&gt;1/250). Fetal karyotyping revealed trisomy 21 in about 9.3% (9/97) of the pregnancies. Our algorithm (Hacettepe System) detected 77.8% (7/9) of Down syndrome cases. Moreover, all of the normal fetal karyotypes were assigned as normal in the Hacettepe System.Conclusion: We have developed an intelligent system using the backpropagation learning algorithm (using triple test variables) to predict trisomy 21.

Risk Factors and Outcomes of Recurrent Pregnancy Loss in Japan.

To clarify the risk factors and pregnancy outcomes for each risk factor of recurrent pregnancy loss (RPL) in Japan. Using a prospective RPL database collected from 16 facilities in Japan, the prevalence of risk factors for RPL, their treatments and pregnancy outcomes were examined. Of 6663 patients registered in our database, 5708 patients had RPL. All examinations for risk factors were performed for 1340 patients (23.5%). The prevalences of positive antiphospholipid antibodies (aPL), malformation of the uterus, thyroid dysfunction, parental karyotype abnormality, factor XII deficiency, protein S deficiency and unknown risk factors were 8.7%, 7.9%, 9.5%, 3.7%, 7.6%, 4.3% and 65.1%, respectively. Although factor XII deficiency and protein S deficiency are not recognized as risk factors for RPL in general, low-dose aspirin (LDA) or unfractionated heparin + LDA therapy improved live birth rates. In transiently aPL-positive patients, the live birth rate with LDA therapy was similar to that with heparin + LDA. For unknown risk factors of RPL, the live birth rate in normal fetal karyotype in the none treatment group was similar to that in all other treatments group (81.3% vs 86.0%). Of 5708 RPL patients, pregnancy outcomes were known for 2261 patients and 1697 patients (75.1%) had at least one live birth. The risk factors and pregnancy outcomes for each risk factor of RPL are useful for clinicians and patients. Factor XII deficiency and protein S deficiency may be risk factors of RPL.

The clinical usefulness of biochemical (free β-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy.

The aim of the study was to analyze the correlation of multiples of the normal median of PAPP-A, free β-hCG levels and nuchal translucency values in prenatal, first trimester screening of trisomy 21 in pregnant women. 251 pregnant women underwent antenatal screening at 11-13+6 weeks of pregnancy which was composed of the measurement of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP-A) levels in the maternal serum and an ultrasound assessment of nuchal translucency (NT). The pregnant women with a high risk of trisomy 21 (≥ 1:300) were given amniocentesis to verify fetal defects. There were 217 cases of normal fetal karyotype and 34 cases of trisomy 21. PAPP-A, β-hCGMoM and NT values were analyzed for the predefined ranges. 85% cases of trisomy 21 had elevated free β-hCGMoM (> 1.5) and only 53% of these had a PAPP-AMoM result below 0.5 (p < 0.05). Analysis of NT in selected ranges of β-hCG (> 1.5) and PAPP-AMoM (< 0.05), which are typical for Down Syndrome values, showed that not all fetuses with Down Syndrome presented with an increased NT. Respectively 44.15% and 26.5% of fetuses presented with increased NT. Characteristic for trisomy 21, a correlation with all 1st trimester screening tests' parameters occurred in only 23.5% of cases. In 53% of cases the results were atypical. The PAPP-A and β-hCG values in the selected MoM ranges did not shown a correlation to the NT measurement, therefore they are independent factors in the diagnosis of trisomy 21. Simultaneous biochemical and ultrasound testing is an indispensable condition for prenatal diagnosis of trisomy 21 in the 1st trimester of pregnancy.

Complication rates after chorionic villus sampling and midtrimester amniocentesis: A 7-year national registry study

To assess the complication rates following chorionic villus sampling (CVS) and midtrimester amniocentesis in Taiwan. This is a national registry-based cohort study from Taiwan. We included all women with singleton pregnancies who received either CVS (n=1409) or midtrimester amniocentesis (n=250,566) during 2006-2012. We assessed preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD), infection and spontaneous abortion (SA) that occurred within fourteen days after the procedures. We also assessed the risks of preterm delivery and miscarriage before 24 gestational weeks after amniocentesis. These complications were collected from the Genetic Disease Database of the Ministry of Health and Welfare, Taiwan National Birth Certificate Registry, and the Taiwan National Health Insurance Database. Pearson χ2 tests were used to compare the distributions between groups. For patients who underwent midtrimester amniocentesis, the rates of PPROM, IUFD, infection and SA within fourteen days were 0.24%, 0.11%, 0.05%, and 0.05%, respectively. Women with a normal fetal karyotype had a preterm birth rate (<37 gestational weeks) of 9.38%. The miscarriage rate (<24 gestational weeks) was 0.68%, which was 0.22% higher than those who did not receive the invasive procedures (p<0.0001). After CVS, the IUFD rate was 1.68%, and the SA rate within fourteen days was 0.77%. The use of our large cohort demonstrated that the procedure-related complication rates were comparable to recent review or meta-analysis. This dataset might facilitate counselling in women who consider invasive genetic diagnostic procedures.