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The cesarean delivery rate has been rising in recent years, having associated maternal morbidities. Elective induction of labor has also been seen to rise during this same time period.This current study investigated the difference in the cesarean delivery rate between induction of labor and spontaneous labor among nulliparous, term, singleton, and vertex-presenting women.A retrospective cohort in a single institution over a seven-year period was used for this analysis, observing the difference in cesarean delivery rate at different term gestational ages and neonatal morbidity using the 5-minute Apgar score5.A statistically significant difference was found in cesarean delivery rate between those women whose labor was induced and those whose labor began spontaneously, at each term gestational age of labor initiation (P 0.001). The proportion of indications for induction was described (i.e. elective vs. medically-indicated), and no difference was found for neonatal morbidity between the groups analyzed, using the 5-minute Apgar score as the perinatal outcome measure.A comparison was made between spontaneous and induced labor regarding the resultant cesarean delivery rate, and a significant difference was found favoring spontaneous labor. This should be considered when electing to deliver using an induction methodology for nulliparous women, especially when there are no medical indications for it.

Recommendations for cervical cancer screening have had remarkable agreement from a number of medical societies, including the American College of Obstetricians and Gynecologists (ACOG), American Cancer Society (ACS), American Society of Cervical Colposcopy and Pathology (ASCCP), and the US Preventative Services Task Force (USPSTF). Reference to the recommended age for screening may need to be re-examined, in light of current data regarding the comparative age-related incidence of cervical malignancy, especially when recognizing the past utility of screening with exfoliative cytology in reducing subsequent mortality. Age and Cervical Cancer Screening Recommendations The recommendations for cervical cancer screening from the US Preventative Services Task Force (USPSTF), 1 the American College of Obstetricians and Gynecologists (ACOG), 2 the American Society of Colposcopy and Cervical Pathology (ASCCP), and the American Cancer Society (ACS) provide for discontinuation of screening for women over 65 years of age, provided that no previous dysplasia was detected in the past 10 years. However, there may be some important findings in the Surveillance, Epidemiology and End Results (SEER) database, which may be worth examining. For example, according to SEER data, from 2004 -2015, the incidence of cervical cancer in patients aged 65 or over was significantly higher than that of young patients (P

Skeletal dysplasia (SD) is a complex group of bone and cartilage disorders often detectable by fetal ultrasound, but the definitive diagnosis remains challenging because the phenotypes are highly variable and often overlap among different disorders. The molecular mechanisms underlying this condition are also diverse. Hundreds of genes are involved in the pathogenesis of SD, but most of them are yet to be elucidated, rendering genotyping almost infeasible except those most common such as fibroblast growth factor receptor 3 (FGFR3), collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), diastrophic dysplasia sulfate transporter (DTDST), and SRY-box 9 (SOX9). Here, we report the use of trio-based whole exome sequencing (trio-WES) with comprehensive gene set analysis in two Taiwanese non-consanguineous families with fetal SD at autopsy. A biparental-origin homozygous c.509G>A(p.G170D) mutation in peptidylprolyl isomerase B (PPIB) gene was identified. The results support a diagnosis of a rare form of autosomal recessive SD, osteogenesis imperfecta type IX (OI IX), and confirm that the use of a trio-WES study is helpful to uncover a genetic explanation for observed fetal anomalies (e.g., SD), especially in cases suggesting autosomal recessive inheritance. Moreover, the finding of an identical PPIB mutation in two non-consanguineous families highlights the possibility of the founder effect, which deserves future investigations in the Taiwanese population.

To offer obstetrical practitioners a current perspective about an important contemporary practice model which has implications that may not have been adequately recognized. A description of individual past professional experience. A resultant perspective from decades of professional obstetric practice. A description of potential clinical impact on patients and practitioners alike.

Background Noninvasive prenatal testing (NIPT) based on cell-free DNA in maternal circulation has been accepted worldwide by the clinical community since 2011 but limitations, such as maternal malignancy and fetoplacental mosaicism, preclude its full replacement of invasive prenatal diagnosis. We present a novel silicon-based nanostructured microfluidics platform named as “Cell Reveal™” to demonstrate the feasibility of capturing circulating fetal nucleated red blood cells (fnRBC) and extravillous cytotrophoblasts (EVT) for cell-based noninvasive prenatal diagnosis (cbNIPD). Methods The “Cell Reveal™” system is a silicon-based, nanostructured microfluidics using immunoaffinity to capture the trophoblasts and the nucleated RBC (nRBC) with specific antibodies. The automated computer analysis software was used to identify the targeted cells through additional immunostaining of the corresponding antigens. The identified cells were retrieved for whole genome amplification for subsequent investigations by micromanipulation in one microchip, and left in situ for subsequent fluorescence in situ hybridization (FISH) in another microchip. When validation, bloods from pregnant women (n = 24) at gestational age 11–13+6 weeks were enrolled. When verification, bloods from pregnant women (n = 5) receiving chorionic villus sampling or amniocentesis at gestation age 11+4–21 weeks with an aneuploid or euploid fetus were enrolled, followed by genetic analyses using FISH, short tandem repeat (STR) analyses, array comparative genomic hybridization, and next generation sequencing, in which the laboratory is blind to the fetal genetic complement. Results The numbers of captured targeted cells were 1–44 nRBC/2 ml and 1–32 EVT/2 ml in the validation group. The genetic investigations performed in the verification group confirmed the captured cells to be fetal origin. In every 8 ml of the maternal blood being blindly tested, both fnRBC and EVT were always captured. The numbers of captured fetal cells were 14–22 fnRBC/4 ml and 1–44 EVT/4 ml of maternal blood. Conclusions This report is one of the first few to verify the capture of fnRBC in addition to EVT. The scalability of our automated system made us one step closer toward the goal of in vitro diagnostics. Electronic supplementary material The online version of this article (10.1186/s13039-017-0343-3) contains supplementary material, which is available to authorized users.

Although co-amplification of polymorphic microsatellite markers is the current gold standard for preimplantation genetic diagnosis (PGD) of single-gene disorders (SGD), this approach can be hampered by the lack of availability of informative markers. We recently (2011) devised a novel in-house assay for PGD of aromatic l -amino acid decarboxylase deficiency, based on an amplification refractory mutation system and quantitative PCR (ARMS-qPCR). The objective of the present study was to verify ARMS-qPCR in a cohort of 20 PGD cycles with a diverse group of SGDs (15 couples at risk for 10 SGDs). Day-3 cleavage-stage embryos were subjected to biopsy and genotyping, followed by fresh embryo transfer (FET). The diagnostic rate was 82.9%; unaffected live births were achieved in 9 of 20 FET cycles (45%), with only one false negative (among 54 transferred embryos). Overall, the ARMS-qPCR had frequent allele-dropout (ADO), rendering it inappropriate as the sole diagnostic method (despite a favorable live-birth rate). Regardless, it has the potential to complement the current gold-standard methodology, especially when trophectoderm biopsy becomes a preferred option and genotyping needs to be timely enough to enable FET.

Objectives Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. Methods In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. Results Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. Conclusion Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Object The authors sought to identify novel biomarkers for early detection of neural tube defects (NTDs) in human fetuses. Methods Amniotic fluid and serum were drawn from women in the second trimester of pregnancy. The study group included 2 women pregnant with normal fetuses and 4 with fetuses displaying myelomeningocele (n = 1), anencephaly (n = 1), holoprosencephaly (n = 1), or encephalocele (n = 1). Amniotic fluid stem cells (AFSCs) were isolated and cultured. The cells were immunostained for the stem cell markers Oct4, CD133, and Sox2; the epigenetic biomarkers H3K4me2, H3K4me3, H3K27me2, H3K27me3, H3K9Ac, and H3K18Ac; and the histone modifiers KDM6B (a histone H3K27 demethylase) and Gcn5 (a histone acetyltransferase). The levels of 2 markers for neural tube development, bone morphogenetic protein–4 (BMP4) and sonic hedgehog (Shh), were measured in amniotic fluid and serum using an enzyme-linked immunosorbent assay. Results The AFSCs from the woman pregnant with a fetus affected by myelomeningocele had higher levels of H3K4me2, H3K4me3, H3K27me2, and H3K27me3 and lower levels of KDM6B than the AFSCs from the women with healthy fetuses. The levels of H3K9ac, H3K18ac, and Gcn5 were also decreased in the woman with the fetus exhibiting myelomeningocele. In AFSCs from the woman carrying an anencephalic fetus, levels of H3K27me3, along with those of H3K9Ac, H3K18ac, and Gcn5, were increased, while that of KDM6B was decreased. Compared with the normal controls, the levels of BMP4 in amniotic fluid and serum from the woman with a fetus with myelomeningocele were increased, whereas levels of Shh were increased in the woman pregnant with a fetus displaying anencephaly. Conclusions The levels of epigenetic marks, such as H3K4me, H3K27me3, H3K9Ac, and H3K18A, in cultured AFSCs in combination with levels of key developmental proteins, such as BMP4 and Shh, are potential biomarkers for early detection and identification of NTDs in amniotic fluid and maternal serum.

The objective of this study is to examine results of bacterial cultures of the cervix prior to cerclage placement and how these may be used to guide prophylactic antibiotics.All patients undergoing cerclage between 2000 and 2003 in a single, large community hospital were evaluated for indication for cerclage, signs and symptoms on presentation, transvaginal ultrasound cervical length findings, type of cerclage placed, type of anesthesia used, cervical culture taken, tocolytics given, gestational age at delivery, and complications surrounding delivery.Sixty-five cerclages were performed between 2000 and 2003, 13 (20%) prophylactic, 47 (72%) therapeutic, and five (8%) emergent. Cervical cultures were obtained in 85% of patients, of which 40% were negative resulting in no antibiotics given. In the remaining 45%, one or more pathogens were isolated and antibiotics were given according to sensitivities reported. Fifty-five of 65 patients (84%) delivered after 32 weeks gestation and a latency 60 d was seen in 84%. The incidence of chorioamnionitis and PPROM was low.Bacterial cultures of the cervix prior to cerclage show variable colonization and antibiotic sensitivities and, there is no single antibiotic, chosen empirically, that will cover all pathogens.

Objective We hypothesize that the rotation of the ear in fetuses with common autosomal trisomies will be markedly different from euploid fetuses and amenable to detection by 3-D ultrasound in the render mode. Methods Study participants (10 weeks 4 days through 19 weeks 0 days) underwent a 3-D rendering of the fetal face and ear along with other biometric measurements prior to invasive testing. Results Of the 348 patients who underwent chorionic villi sampling (CVS) (n = 208) or amniocentesis (n = 140), 18 were diagnosed with trisomy 21, 4 with trisomy 18, and 1 with trisomy 13. Mean gestational age was 12 weeks 6 days (range: 10 weeks 6 days to 19 weeks 0 days). Ear angles were obtained in all cases; the time to obtain this angle ranged from 5 to 25 min. Thirty-two fetuses were found to have an abnormal ear angle with 23 of the 32 characterized by one of the aforementioned trisomies. Conclusions These findings support the potential of this technique to provide valuable information in the identification of an increased-risk population. Prospective studies are needed to confirm the value of this screening modality as well as to assess its facility and ability to be incorporated into routine obstetrical practice. Copyright © 2011 John Wiley & Sons, Ltd.

Objective Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (α-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. Method We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. Results We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. Conclusion These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population. Copyright © 2009 John Wiley & Sons, Ltd.

To determine whether women with recurrent evidence of cervical insufficiency (CI) and with a history-indicated cerclage (HIC) placed at the beginning of the second trimester will deliver later than the index case.Retrospective case-control study of singleton pregnancy with history-consistent CI. Patients had a cerclage placed between 12 and 16 weeks of gestation. Transvaginal cervical measurement was done between 18 and 24 weeks. Those with a cervical measurement 25 mm were considered to have recurrent CI (Group A). Gestational age at delivery of the index case (Group C) and the cerclage patients (Groups A and B), which are the same patients as Group C, was compared using Student's t test. They have the same genetics and anatomy.A total of 124 women had an HIC. Sixteen (13%) had recurrent CI (Group A). Comparing cases, the proximate average age at delivery was 22 weeks as compared with 33 weeks and 3 days for those with a cerclage (p0.001) (Group A vs. B). In those with a cervical length25 mm (Group B), 96 (89%) had a term delivery. In the index cases 64% delivered at 22 weeks or less (Group C).Cerclage in those patients with recurrent CI has a significantly improved outcome as compared with the index case. This minimizes pregnancy loss.

Objective: To identify the risk factors for perioperative venous thromboembolism, and the possible consequences of pharmacologic thromboprophylaxis used with cesarean delivery. Study design: An Enterprise Data Warehouse (EDW) of a multi-hospital system was queried to obtain the incidence of and risk factors for perioperative venous thromboembolism (VTE) and the use of pharmacologic thromboprophylaxis (PTP). Results: Of 337,174 surgical patients over the course of 2010-2013, Cesarean Delivery (CD) occurred 24,608 times, with pharmacologic VTE prophylaxis (PTP) being provided 931 times (4% of the time) and 23,677 times without such prophylaxis. Hemorrhagic complications were recorded 0.08% of the time (0.3% when PTP was provided, and 0.08% without it). As this was found to be statistically significant (p=0.02), this warrants our concern, regarding the appropriateness of using PTP for all cesarean deliveries. Conclusion: Pharmacologic thromboprophylaxis may have the risk of associated hemorrhage with its use, and it may be worthwhile to use risk stratification to decide whether or not to use it for surgical prophylaxis in particular cesarean cases.

Objective To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. Design Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. Results On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall ( P = 0.9759). In contrast, those who received additional intervention showed a marked difference ( P < 0.0001). Conclusions Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

Objective: Our aim was to determine the rate and risk factors for recurrent shoulder dystocia. Study Design: A retrospective analysis of patients diagnosed with shoulder dystocia was performed by searching a computerized database from January 1, 1993, to June 30, 1999 for the following information: (1) vaginal deliveries, either spontaneous or operative, (2) shoulder dystocia, (3) birth weight, (4) duration of second stage of labor, (5) parity, and (6) gestational diabetes. Statistical analyses included χ2 and t test. Results: There were 39,681 vaginal deliveries with 602 (1.5%) complicated by shoulder dystocia. Sixty-six patients underwent a subsequent vaginal delivery, and 11 (16.7%) experienced another shoulder dystocia. The odds ratio for a recurrent shoulder dystocia was 10.98 (P < .000001). Nine of the 11 patients with recurrent shoulder dystocia compared with 28 of 55 without a recurence were nulliparous women in their index pregnancy (P < .001). The mean fetal weights were 3885 g in the recurrent dystocia group and 3702 g in the group without recurrence (P < .03). Gestational age, operative delivery, and gestational diabetes were similar in the two groups. Conclusion: Factors that appear to increase the recurrence risk of shoulder dystocia include fetal weight and maternal parity. Prior shoulder dystocia is the single greatest predictive factor. (Am J Obstet Gynecol 2001;184:1427-30.)

Purpose: We previously demonstrated that aneuploidy-free oocytes may be preselected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. The present paper describes the results of the application of the method in 659 in vitro fertilization cycles from patients of advanced maternal age. Methods: Using micromanipulation techniques, 3943 oocytes were tested by polar body sampling and fluorescent in situ hybridization analysis using specific probes for chromosomes 13, 18, and 21. Results: Fluorescent in situ hybridization results were available for 3217 (81.6%) of 3943 oocytes studied, of which 1388 (43.1%) had aneuploidies; 35.7% of the aneuploidies were of first meiotic division origin, and 26.1% of second meiotic division origin. Most errors in the first meiotic division were represented by chromatid malsegregation. The transfer of embryos deriving from 1558 of 1829 aneuploidy-free oocytes in 614 treatment cycles resulted in 131 clinical pregnancies and 88 healthy children born after confirmation of the polar body diagnosis. Conclusions: Polar body testing of oocytes provides an accurate and reliable approach for prevention of age-related aneuploidies in in vitro fertilization patients of advanced maternal age.

OBJECTIVE: The purpose of this study was to determine the accuracy and feasibility of sequential polar body removal and analysis for preimplantation genetic diagnosis of mendelian disorders. STUDY DESIGN: Three couples with risk factors for cystic fibrosis had preimplantation genetic diagnosis with the use of sequential polar body analysis. After stimulation, oocytes were harvested and the first polar bodies were removed and analyzed on the day of aspiration. The following day, after fertilization, the second polar bodies were aspirated. Only embryos known to have inherited the normal maternal allele were transferred. RESULTS: All three couples had successful pregnancies resulting in the births of unaffected infants. CONCLUSIONS: Preimplantation diagnosis with the use of sequential polar body removal is feasible and can prevent the establishment of genetically abnormal pregnancies for couples at risk. (Am J Obstet Gynecol 1998;178:1298-306.)

Purpose:A low pregnancy rate in in vitro fertilization (IVF) patients of advanced maternal age may be caused by aneuploidies originating from non disjunction in the first or second meiotic divisions. We introduced genetic testing of oocytes by sampling and fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies, to avoid fertilization and transfer of aneuploid oocytes in IVF patients of advanced maternal age. Methods:Three hundred and sixty-three IVF patients 34 years and older participated in the study. Using micromanipulation procedures, the first and second polar bodies were removed following their extrusion from the oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21 to detect oocytes with common aneuploidies. Results:Of a total of 538 IVF cycles, 3250 oocytes were available for FISH analysis, with conclusive FISH results in 2742 oocytes (84.3%). As many as 1102 (40%) of oocytes were predicted to be aneuploid and not transferred. Of 1640 embryos predicted to be normal, 1145 were transferred in 467 treatment cycles, resulting in 107 pregnancies (23%), from which 67 healthy children have been born, 32 pregnancies spontaneously aborted, and 15pregnancies are ongoing after being confirmed normal by prenatal diagnosis. Conclusions:Preimplantation diagnosis by first- and second-polar body FISH analysis allows us to avoid the age-related risk of common aneuploidies in IVF patients of advanced maternal age.

OBJECTIVES: Our purpose was to determine the feasibility and optimal techniques for prenatal paternity testing. STUDY DESIGN: Since January 1989 we have offered prenatal paternity testing by deoxyribonucleic acid testing. We analyzed the ability to complete the testing and the time required to complete the testing and developed polymerase chain reaction - based tests to speed test results. RESULTS: Before April 1990 only five of nine cases could be completed. Since that time 28 consecutive cases were successfully completed before delivery. Introduction of polymerase chain reaction - based testing has allowed us to perform testing on uncultured chorionic villi and to derive results within 3 weeks. CONCLUSION: Analysis of uncultured chorionic villi allows prenatal paternity testing to be completed within the first trimester of pregnancy. Prenatal paternity testing can also be performed on cultured amniocytes and chorionic villi. (Am J Obstet Gynecol 1996;174:1849-54.)

The purpose of this work was to investigate the reliability and accuracy of polar body analysis for preimplantation diagnosis of common aneuploidies in IVF patients of advanced maternal age.We have previously introduced polar body analysis as an approach for nondestractive evaluation of the genotype of human oocytes. The method has recently been applied in a clinical trial involving 45 infertile patients, demonstrating the feasibility of preconception diagnosis of common aneuploidies by fluorescent in situ hybridization (FISH). The present paper describes the experience of polar body diagnosis in 135 IVF patients (161 cycles) of advanced maternal age.FISH results of the first and/or second polar bodies were available in 648 (72.4%) of 895 biopsied oocytes subjected to FISH analysis. Of 648 oocytes with FISH results, 208 demonstrated chromosomal abnormalities. Of 440 oocytes predicted to be free from monosomy or trisomy of chromosomes X, 18, and/or 13/21, 314 were normally fertilized, cleaved, and transferred in 122 treatment cycles, resulting in 6 healthy deliveries and 12 ongoing pregnancies following confirmation of the polar body diagnosis by CVS or amniocentesis.The method may be useful for detection of oocytes with common chromosomal trisomies in IVF patients of advanced maternal age.

In a routine application of commercially available centromeric DNA probes for the prenatal screening of common trisomies involving the autosomes 13, 18, and 21, and sex chromosomes, four cases of discrepancy between fluorescence in situ hybridization (FISH) results and follow-up cytogenetic analysis were observed from a total of 516 cases of amniocentesis. In three of these cases, the results were false negative, and in one false positive. In this case, amniocentesis was performed because of a positive triple test in a 34-year-old woman with previous infertility treatment. The alpha satellite DNA probe for chromosomes 13/21 revealed five signals in 50 per cent of uncultured amniocytes, while standard cytogenetic analysis showed a normal karyotype. FISH analysis on metaphase chromosomes demonstrated the location of the additional signal in the centromeric region of chromosome 22. This additional signal was also present in the centromeric region of chromosome 22 of the mother, providing evidence for a possible inherited polymorphism in chromosome 22 responsible for unspecific hybridization with the alpha satellite probe for chromosomes 13/21 in this case. The observed polymorphism in centromeric regions may contribute to unreliability of the use of the 13/21 alpha satellite probe for prenatal screening by FISH.

Chromosomal aneuploidies contribute considerably to the low pregnancy rate in in-vitro fertilization (IVF). The objective of this experimental work was to explore the possibility of detecting common aneuploidies in oocytes by polar body sampling. The study included 45 infertile patients of advanced maternal age participating in an IVF programme. The first polar body was removed prior to fertilization or both the first and second polar bodies were removed after fertilization and studied by fluorescent in-situ hybridization (FISH) using chromosome-specific probes for chromosomes X, 18 and/or 13/21. Of 155 oocytes with FISH results, 36 demonstrated chromosomal abnormalities. Of 119 oocytes predicted to be free from aneuploidy of chromosomes X, 18 and/or 13/21, 72 were normally fertilized, cleaved and transferred in 23 treatment cycles, which resulted in two healthy deliveries and three ongoing pregnancies confirmed to be unaffected by chorionic villous sampling. The method may appear useful for the detection of oocytes with common chromosomal aneuploidies in IVF patients of advanced maternal age.

Fetal chylothorax (FC) is a rare condition characterized by lymphocyte-rich pleural effusion. Although its pathogenesis remains elusive, it may involve inflammation, since there are increased concentrations of proinflammatory mediators in pleural fluids. Only a few hereditary lymphedema-associated gene loci, e.g. VEGFR3, ITGA9 and PTPN11, were detected in human fetuses with this condition; these cases had a poorer prognosis, due to defective lymphangiogenesis. In the present study, genome-wide gene expression analysis was conducted, comparing pleural and ascitic fluids in three hydropic fetuses, one with and two without the ITGA9 mutation. One fetus (the index case), from a dizygotic pregnancy (the cotwin was unaffected), received antenatal OK-432 pleurodesis and survived beyond the neonatal stage, despite having the ITGA9 mutation. Genes and pathways involved in the immune response were universally up-regulated in fetal pleural fluids compared to those in ascitic fluids. Furthermore, genes involved in the lymphangiogenesis pathway were down-regulated in fetal pleural fluids (compared to ascitic fluid), but following OK-432 pleurodesis, they were up-regulated. Expression of ITGA9 was concordant with overall trends of lymphangiogenesis. In conclusion, we inferred that both the immune response and lymphangiogenesis were implicated in the pathogenesis of fetal chylothorax. Furthermore, genome-wide gene expression microarray analysis may facilitate personalized medicine by selecting the most appropriate treatment, according to the specific circumstances of the patient, for this rare, but heterogeneous disease.

Objectives To compare crown–rump lengths with karyotypes of missed miscarried fetuses and to determine a relationship between crown–rump length and trisomy 21. Study design Chorionic villus sampling was performed on 129 consecutive missed miscarriages between 10 and 12 weeks by last menstrual period in patients ≥ 35 years of age. Crown–rump length was correlated with the karyotype. Statistical analysis was performed using Student's t-test. Results Twenty-one of 129 missed miscarriages involved fetuses affected by trisomy 21. The crown–rump length was < 22 mm in 77% of missed miscarriages. Using a crown–rump length of ≥ 22 mm for the prediction of trisomy 21 had a sensitivity of 86%, specificity of 89%, positive predictive value of 60% and negative predictive value of 97%. At 10–12 weeks, the crown–rump lengths of missed miscarried fetuses with trisomy 21 was significantly larger (P ≤ 0.0001) than that of the population average of missed miscarried fetuses. Conclusion In women ≥ 35 years of age, with a missed miscarriage, in whom pregnancies reached ≥ 10 weeks from the last menstrual period, a fetal crown–rump length of ≥ 22 mm has a high probability that the etiology of the loss will be secondary to trisomy 21. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Aneuploidy free oocytes may be pre-selected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. We present here our experience on the application of the method in IVF cycles from patients of advanced maternal age. Overall, 5590 oocytes were obtained from 917 cycles and tested by polar body sampling and fluorescent in situ hybridization (FISH) analysis using specific probes for chromosomes 13, 16, 18, 21 and 22. FISH results were available in 4599 (82.2%) of 5590 oocytes studied, from which 2077(45.2%) were with aneuploidies. Thirty six point one percent of aneuploidies were of the first meiotic origin, and 29.3% of the second meiotic origin. Most errors in the first meiotic division were represented by chromatid errors. The transfer of embryos deriving from 2014 of 2520 aneuploidy free oocytes in 821 treatment cycles resulted in 182 (22.2%) clinical pregnancies and 140 healthy children born after confirmation of the polar body diagnosis. Polar body testing of oocytes provides an approach for pre-selection of aneuploidy free embryos, improving pregnancy rate in IVF patents of advanced maternal age.

We hypothesize that the rotation of the ear in fetuses with common autosomal trisomies will be markedly different from euploid fetuses and amenable to detection by 3-D ultrasound in the render mode.Study participants (10 weeks 4 days through 19 weeks 0 days) underwent a 3-D rendering of the fetal face and ear along with other biometric measurements prior to invasive testing.Of the 348 patients who underwent chorionic villi sampling (CVS) (n = 208) or amniocentesis (n = 140), 18 were diagnosed with trisomy 21, 4 with trisomy 18, and 1 with trisomy 13. Mean gestational age was 12 weeks 6 days (range: 10 weeks 6 days to 19 weeks 0 days). Ear angles were obtained in all cases; the time to obtain this angle ranged from 5 to 25 min. Thirty-two fetuses were found to have an abnormal ear angle with 23 of the 32 characterized by one of the aforementioned trisomies.These findings support the potential of this technique to provide valuable information in the identification of an increased-risk population. Prospective studies are needed to confirm the value of this screening modality as well as to assess its facility and ability to be incorporated into routine obstetrical practice.

In women who are heterozygous for a genetic disease, genetic analysis of the first polar body allows the identification of oocytes that contain the maternal unaffected gene. These oocytes can be fertilized and transferred to the mother without risk of establishing a pregnancy with a genetically abnormal embryo. We have demonstrated that removal of the first polar body has no effect on subsequent fertilization rates or embryonic growth to the blastocyst stage. We have developed a PCR technique to successfully analyze the PI type Z and PI type M genotypes of alpha-1-antitrypsin deficiency and applied this technique for a couple at risk for PI type ZZ alpha-1-antitrypsin deficiency. After standard IVF treatment to stimulate multiple follicle development, eight oocytes were aspirated transvaginally. Polar bodies were removed by micromanipulation from seven oocytes and fertilization occurred in six cases. PCR analysis was successful in five oocytes. One was PI type M, two were PI type Z and two were heterozygous MZ due to crossing over. Embryos from the two oocytes containing the unaffected gene (polar body PI type Z) were transferred in the same cycle 48 h after insemination. No pregnancy was established. The accuracy of the polar body diagnosis was confirmed by polymerase chain reaction (PCR) analysis of an oocyte that failed to fertilize.

In the application of the fluorescence in situ hybridization (FISH) technique for prospective prenatal screening of common aneuploidies involving the autosomes 13, 18, and 21, and sex chromosomes, six cases of inconsistency between the results of FISH analysis and the results of karyotyping of cultured amniocytes have been observed, including two cases of translocation involving the Y-chromosome and chromosome 15 in a total of 904 cases of amniocentesis studied. In one case, the translocation was of maternal origin, and in the other, of paternal origin. In both cases, the couples decided to continue the pregnancy and normal babies were delivered. The data show the usefulness of applying the FISH technique in prospective prenatal screening of common trisomies for the possible detection of rare chromosome rearrangements involving the Y-chromosome.

Counseling for pyelectasis in the late 2nd trimester is usually based only upon assessing the antero-posterior (AP) width of the renal pelvis. We hypothesized that checking additional features would better predict postnatal outcome.Ultrasound (24 weeks gestational age (GA)) and newborn outcome data collected prospectively since 1986 were analyzed retrospectively. We determined if outcome predictions in kidneys with a sonographically evident renal pelvis (SERP), which had evaluation of additional features (e.g., renal and bladder lengths, presence of a dilated ureter or dilated calyces) are more accurate than those that did not have these features.There were 286 fetuses studied with pediatric follow-up of an average of 6.5 years. There were 338 exams providing 459 ultrasound images with SERP. Additional features were not assessed in 183 fetuses; however 103 fetuses did have evaluation of additional features. These features were categorized as abnormal (92) or as normal (11). Fetuses with SERP and abnormal additional features required extensive urological care or died 6.1 times more often than fetuses in which additional features were not examined (p0.001) and 12.9 times more often when additional features were normal (p0.001).Fetal kidneys with SERP (24 weeks GA) and an abnormal additional ultrasound feature had extensive pediatric care significantly more often than when such features were not evaluated or were normal.

Arteriovenous malformation of the uterus is a rare uterine abnormality. This entity is generally associated with the presence of molar disease, choriocarcinoma and uterine surgery, but may be congenitally acquired. The presence of an arteriovenous malformation generally leads to unexplained profuse uterine bleeding. The diagnosis of this entity has traditionally been made by arteriography, and the treatment is usually hysterectomy. We present a patient with an arteriovenous malformation of the uterus whose prior delivery was by Cesarean section. The patient experienced episodes of heavy vaginal bleeding in the first month following the procedure of suction curettage for a first-trimester pregnancy loss. Chorionic villus sampling performed prior to the procedure showed a chromosomally normal fetus. The diagnosis of an arteriovenous malformation was made by color Doppler velocimetry and confirmed with arteriography. The patient desired to maintain her fertility. Interventional radiological techniques were successfully utilized to obliterate the arteriovenous malformation with the use of polyvinyl alcohol particles (250 micro m) and gelfoam. Discussion includes the presenting signs and symptoms along with the method of both diagnosis and conservative management.

Objective: We sought to determine whether preimplantation genetic diagnosis is associated with particular pregnancy or delivery complications. Study Design: A total of 102 consecutive pregnancies after preimplantation genetic diagnosis by polar body removal performed at Illinois Masonic Medical Center resulting in 114 live births were analyzed. All patients were given a delivery and newborn questionnaire, and attempts were made to contact and question them regarding any pregnancy complications and type of delivery. Permission was obtained to examine medical records and discuss the patient's pregnancy with her obstetrician when questions existed with respect to complications or indication for cesarean delivery. Results: Delivery and newborn questionnaires were completed or telephone contact was achieved for 100 of the 102 pregnancies. There were 85 singleton, 9 twin, and 7 triplet pregnancies. Of the 7 triplet gestations, 3 couples elected multifetal pregnancy reduction to twins and healthy triplets were born to 4 couples between 32 and 36 weeks by cesarean delivery. Of the 80 singleton deliveries, 60 (75%) progressed to term. Of these 60 term singleton deliveries, 34 were vaginal, 23 were cesarean (40%), and 3 delivery types were unknown. The incidence of small-for-gestational-age infants was 3% for neonates in the 60 term singleton deliveries and 7% in the entire cohort of 80 singleton deliveries. Only 3 pregnancy complications (other than premature delivery) were reported more than once. There were 3 instances each of gestational diabetes, intrauterine growth restriction, and pregnancy-induced hypertension. There was 1 case each of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, congestive heart failure, mild oligohydramnios, and abruptio placentae. The indications for cesarean delivery were (in descending order) failure of labor to progress (n = 7), fetal distress (n = 4), placenta previa (n = 4), elective repeat cesarean delivery (n = 4), triplets (n = 3), uterine scarring (n = 3), 1 twin in the breech position (n = 3), failed forceps delivery (n = 2), and a variety of other indications that occurred in only 1 patient each. All preimplantation genetic diagnoses were confirmed by prenatal or postnatal testing. No diagnostic errors were made in this cohort of patients or in any patients undergoing preimplantation genetic diagnosis having polar body removal in our center. Conclusions: Preimplantation genetic diagnosis is associated with a risk of multiple gestations, cesarean delivery, and placenta previa. Cesarean delivery rates and multiple gestation rates are comparable to those of patients undergoing in vitro fertilization in general. The preimplantation genetic diagnosis itself does not seem to cause an increased risk for any particular pregnancy complication, with the possible exception of placenta previa, which was seen in 4% of patients. (Am J Obstet Gynecol 2000;182:1629-32.)

Accumulated experience of 138,996 cases of chorionic villus sampling shows that chorionic villus sampling is a safe procedure with an associated fetal loss rate comparable to that of amniocentesis. The chorionic villus sampling registry shows that chorionic villus sampling is currently performed primarily between 9 and 12 weeks' gestation and carried no increased risk of limb reduction defects: the overall incidence of limb reduction defects after chorionic villus sampling is 5.2 to 5.7 per 10,000, compared with 4.8 to 5.97 per 10,000 in the general population. Analysis of the pattern distribution of limb defects after chorionic villus sampling revealed no difference from the pattern in the general population. This applies specifically to transverse limb defects. Together with the overall incidence of limb reduction defects, these data provide no evidence for any risk for congenital malformation determined by chorionic villus sampling. Because chorionic villus sampling is currently performed generally after 8 completed weeks of pregnancy, few data are available for analysis of complications related to earlier procedures. Avoiding early chorionic villus sampling also excludes sampling in cases of early fetal death, which can be diagnosed reliably by ultrasonography at 9 weeks of pregnancy.

Our purpose was to determine the incidence of chromosomal aneuploidy in first-trimester pregnancy losses using chorionic villus sampling (CVS). All patients presenting for CVS with no fetal cardiac activity were offered CVS. Cytogenetic results were completed in 95 of 96 cases (99%). Eighty-three percent of the karyotypes were aneuploid. The 16 euploid fetuses had no excess of females. CVS is the most reliable method of determining the karyotype of spontaneously aborted fetuses. The incidence of aneuploidy is much greater than in previous reports that analyzed passed products of conception. CVS should be offered to women who present with first-trimester spontaneous abortions.

Objective: Our aim was to determine whether hysterotomy and selective removal of an acardiac twin could improve the outcome of the "pump" twin. Study Design: A literature and case review of the outcome of the acardiac twin malformation was performed. When an acardiac malformation was diagnosed at 19 weeks' gestation the patient was monitored with weekly ultrasonographic examinations. At 23 weeks' gestation, no blood flow could be demonstrated to the acardiac twin and it was thought that the continued presence of the acardiac twin posed a risk to the "pump" twin. A midtrimester hysterotomy was performed and the acardiac twin was delivered. Results: After the midtrimester hysterotomy, the pregnancy progressed to term and a healthy female infant was delivered by elective cesarean section at 37 weeks' gestation. Conclusion: Midtrimester hysterotomy may be a useful intervention in cases of twinning when one fetus is a threat to the health of the other.

Chorionic villus sampling (CVS) in the first trimester of pregnancy provides a safe and effective method for the early prenatal diagnosis of cytogenetic abnormalities in multiple gestations. In this multicentre study involving 126 twin and 2 triplet gestations primarily at risk because of advanced maternal age, the overall success rate of obtaining an adequate villus sample from each fetus was 99.2 per cent. For women of advanced maternal age, the rate of combined losses of chromosomally normal fetuses due to spontaneous abortion, stillbirths, and neonatal deaths was 5.0 per cent, compared with a 4.0 per cent total loss rate following CVS in singleton pregnancies derived from the same population (Rhoads et al., 1989). There was a 100 per cent success rate in obtaining a cytogenetic analysis; a cytogenetic abnormality was present in five of the multiple gestations (3.9 per cent) and involved seven fetuses (2.7 per cent). There were no diagnostic errors and no cases of normal cytogenetic diagnosis followed by the birth of a cytogenetically abnormal newborn. Based on cases of XX/XY admixture, cell contamination derived either from maternal decidua or the other twin occurred in 6 of 256 samples (2.3 per cent), giving an overall estimate of the frequency of cell contamination of 4.6 per cent; these cases did not present a diagnostic problem. However, there were two cases (0.8 per cent) in which the fetal sex was incorrect, due either to complete maternal cell contamination or to the possibility that in error one twin was sampled twice.