20-year experience on prenatal diagnosis in a reference university medical genetics center in Turkey

Background/aim: Although cutting edge procedures such as cell-free fetal DNA isolation from maternal blood are now available, invasive prenatal tests are still being used extensively for prenatal diagnosis. The study aims to evaluate the demographic data, indications, and cytogenetic results of 9297 results of patients who underwent prenatal invasive testing for genetic analysis that were referred for the last 20 years in a University Medical Genetics Center. Materials and methods: The records of 8363 amniocenteses, 626 chorionic villus, and 308 cordocenteses samples were retrospectively evaluated and analyzed regarding referral reasons, indications and their cytogenetic results. The total numbers and the percentages of each group were recorded; Chi-square and logistic regression analyses were performed to give the statistical likelihood of different events. Results: The number of referrals decreased significantly after 2009. Risk of having trisomy 21 as well as trisomy 13 and 18 significantly increased in parallel with advanced maternal age. When the 21­25 age group was compared to the older age groups in terms of having a trisomy 21 pregnancy, the risk doubled in the 36­40, 5 times higher in 41­45 and 10-fold in 46­50 age groups. No significant linear correlation between maternal serum screening test results and trisomy 21 was found, however the difference between the pregnancies whom cut-off value above and below 1/250 in maternal serum screening test were significant. Conclusion: These data have provided useful information on the frequency of referrals to the reference genetics department, and the feasibility of genetic services. By reviewing the indications and their corresponding results, we can offer invaluable insights that will be useful in genetic counseling and also in the development of more effective genetic strategies.

Laparoscopic view of endosalpingiosis in a woman with dermoid cyst and endometriosis

Endosalpingiosis is, like endometriosis, the presence of cystic masses outside of the salpinx which contains fallopian tube epithelium. Endosalpingiosis can be seen on the surface of ovaries, tubal serosa, uterine serosa, myometrium, and also in the bladder. The main clinical features of endosalpingiosis are pelvic pain, adnexal mass which mimics cancer, and urinary symptoms. Herein, we present a surgical video of endosalpingiosis in a woman with endometriosis and a dermoid cyst.

MicroRNA Expression Profile in the Prenatal Amniotic Fluid Samples of Pregnant Women with Down Syndrome.

BACKGROUND: Down syndrome, which is the most common human chromosomal anomaly that can affect people of any race and age, can be diagnosed prenatally in most cases. Prenatal diagnosis via culture method is time-consuming; thus, genetic analysis has thus been introduced and is continually being developed for rapid prenatal diagnosis. For this reason, the effective use of microRNA profiling for the rapid analysis of prenatal amniotic fluid samples for the diagnosis of Down syndrome was investigated. AIMS: To evaluate the expression levels of 14 microRNAs encoded by chromosome 21 in amniotic fluid samples and their utility for prenatal diagnosis of Down syndrome. STUDY DESIGN: Case-control study. METHODS: We performed invasive prenatal testing for 56 pregnant women; 23 carried fetuses with Down syndrome, and 33 carried fetuses with a normal karyotype. Advanced maternal age and increased risk for Down syndrome in the screening tests were indications for invasive prenatal testing. The age of gestation in the study and control groups ranged between 17 and 18 weeks. The expression levels of microRNA were measured by real-time polymerase chain reaction. RESULTS: The expression levels of microRNA-125b-2, microRNA-155, and microRNA-3156 were significantly higher in the study group than in the control group. CONCLUSION: The presence of significantly dysregulated microRNAs may be associated with either the phenotype or the result of abnormal development. Further large-scale comparative studies conducted in a variety of conditions may bring novel insights in the field of abnormal prenatal conditions.

A Novel Atraumatic Tourniquet Technique for Excessive Bleeding during Cesarean Sections.

Objective. Controlling excessive bleeding in cesarean sections which may cause a life-threatening event even under well-prepared conditions. We used a novel atraumatic tourniquet technique to temporary arrest blood flow through the uterine and ovarian vessels and compare with other techniques. Toothless vascular clamps were used as clamp. Methods. Tourniquet technique performed postpartum hemorrhage (PPH) cases (19 out of 37) were compared with 18 other cases with PPH. Results. The difference between preoperative and postoperative hemoglobin values was significantly lower in the study group as well as the number of blood products needed during and after surgery. Conclusions. This technique not only prevented massive bleeding from the uterus but also allowed physicians time to consider the necessity of further interventions.

Prenatal Evaluation of MicroRNA Expressions in Pregnancies with Down Syndrome.

BACKGROUND: Currently, the data available on the utility of miRNAs in noninvasive prenatal testing is insufficient in the literature. We evaluated the expression levels of 14 miRNAs located on chromosome 21 in maternal plasma and their utility in noninvasive prenatal testing of Down Syndrome. METHOD: A total of 56 patients underwent invasive prenatal testing; 23 cases were carrying Down Syndrome affected fetuses, and 33 control cases carrying unaffected, normal karyotype fetuses were included for comparison. Indications for invasive prenatal testing were advanced maternal age, increased risk of Down Syndrome in screening tests, and abnormal finding in the sonographic examination. In both the study and control groups, all the pregnant women were at 17th and 18th week of gestation. miRNA expression levels were measured using real-time RT-PCR. RESULTS: Significantly increased maternal plasma levels of miR-3156 and miR-99a were found in the women carrying a fetus with Down Syndrome. CONCLUSION: Our results provide a basis for multicenter studies with larger sample groups and microRNA profiles, particularly with the microRNAs which were found to be variably expressed in our study. Through this clinical research, the utility of microRNAs in noninvasive prenatal testing can be better explored in future studies.

Mannose-binding lectin may affect pregnancy outcome.

Mannose-binding lectin (MBL) is a component of the innate immune system and acts as a complement activator through the lectin pathway. Genetic variations of MBL and low MBL levels cause several infection problems, which may also be related to pregnancy problems. We aimed to investigate the role of MBL gene codon 54 polymorphism and serum MBL levels in pregnancy problems and premature delivery. In this prospective study, MBL gene codon 54 polymorphism and serum MBL levels were studied in 45 mothers who delivered earlier than 35 gestational weeks. The frequency of MBL gene codon 54 variant allele B was much higher (homozygous 4.4% and heterozygous 33.3%) in the study group mothers than the previously reported frequency in the healthy Turkish population (homozygous 2-6%, heterozygous 12-20%). MBL variant allele B frequency was closely related to low MBL levels (<0.1 µg/ml), vaginitis and increased IL-6 levels. The median MBL levels were lower than the critical level of 0.1 µg/ ml in study mothers who had recurrent miscarriage, infertility, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membranes with duration of longer than 72 hours, tocolysis, histological chorioamnionitis, urinary tract infection and vaginitis. MBL gene codon 54 variant allele B is related to low serum MBL levels, increased IL-6 levels, genitourinary infections and may cause pregnancy-related problems such as infertility, recurrent miscarriage and preterm delivery.

The disappearing brain-sparing effect in early-onset fetal growth restriction fetuses revisited.

OBJECTIVE: To evaluate the association between the brain-sparing situation and perinatal outcomes in fetuses with early-onset fetal growth restriction (EO-FGR) with absent or reverse end-diastolic flow in the umbilical artery (UA A/REDF). METHODS: We evaluated fetuses with EO-FGR who had patterns of UA A/REDF without abnormal venous Doppler indices. Participants were divided into two groups according to measurements of mid-cerebral artery pulsatility index (MCA PI) just before delivery. Group 1 (n = 45) included those with a brain-sparing effect (BSE) (a MCA PI <5th percentile for the gestational age) and group 2 (n = 14) included those with a disappearing BSE, defined as an MCA PI increase towards normal values after the BSE detected at the initial evaluation. Short-term perinatal outcomes were analyzed. RESULTS: Compared to group 1, group 2 had a significantly low birth weight (p = 0.018) and high rates of extended neonatal intensive care unit hospitalization (p = 0.049 respectively). CONCLUSION: On the basis of longitudinal measurements of MCA PI, increases after the reduction <5th percentile might be related to poor perinatal outcomes in fetuses with EO-FGR who had UA A/REDF without abnormal venous flow patterns.

The effects of different hormone treatment on endothelial function in healthy postmenopausal women.

We aimed to compare the effects of different types of hormone treatment (HT) on endothelial function by means of brachial artery ultrasonographic examination in postmenopausal women. Sixty-two healthy postmenopausal women were included in this study. Subjects were assigned to one of the five groups receiving 6 months of treatment [estrogen (conjugated estrogen), estrogen (conjugated estrogen) plus progesterone (medroxyprogesterone acetate; MPA), raloxifene, tibolone or control]. Endothelial function was assessed by measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. At the end of 6 months, FMD values were found to be significantly increased in women with HT use than the control group (p = 0.001). In subgroups, FMD increased significantly in the estrogen [12 ± 7 versus 25 ± 8, p = 0.001] and raloxifene groups [7 ± 5 versus 11 ± 3, p < 0.01] compared to tibolone and estrogen plus progesterone groups. In conclusion, endothelial function is impaired in postmenopausal women. Both estrogen and raloxifene regimens may improve endothelial functions in healthy postmenopausal women. The direct protective effects of these HT on the healthy endothelium may be more remarkable than the favorable effects on lipid profile.

Prenatal diagnosis of infantile myofibromatosis of the lung: a case report and review of the literature.

We present a case of infantile myofibromatosis of the lung detected at 32 weeks' gestation. The fetus was monitored with weekly ultrasound examinations measuring the mass size and amniotic fluid index. On day 2 after delivery, due to respiratory distress, an exploratory thoracotomy was undertaken and the mass was resected.

Massive secondary postpartum hemorrhage with uterine artery pseudoaneurysm after cesarean section.

Uterine artery pseudoaneurysm is a rare but serious complication of cesarean section. If inadequately treated, it can lead to life-threatening postpartum hemorrhage. Herein, we report the case of a 28-year-old woman who developed secondary postpartum hemorrhage resulting from uterine artery pseudoaneurysm and cesarean scar dehiscence after cesarean section. Angiographic embolization is a safe and effective procedure for treating postpartum hemorrhage resulting from pseudoaneurysm in hemodynamically stable patients. However, uterine artery ligation may be the surgical procedure of choice for hemodynamically unstable patients when fertility preservation is desired.

Combination of intracranial translucency and 3D sonography in the first trimester diagnosis of neural tube defects: case report and review of literature.

Neural tube defects are congenital defects of the central nervous system caused by lack of neural tube closure. First trimester screening for aneuploidy has become widespread in the recent years. Fetal intracranial translucency (IT) can be easily observed in normal fetuses in the mid-sagittal plane. The absence of IT should be an important factor taken into consideration in the early diagnosis of open spinal defects. 3D ultrasonography is especially useful in cases of spinal anomalies where the visualization of the fetal structure is insufficient due to fetal position. We present a combination of intracranial translucency and 3D sonography used in the first trimester diagnosis of a neural tube defect case.

Fetal aortic isthmus Doppler measurements for prediction of perinatal morbidity and mortality associated with fetal growth restriction.

OBJECTIVE: To identify the role of longitudinal measurements of fetal aortic isthmus blood flow using Doppler ultrasonography in the prediction of perinatal morbidity and mortality. SETTING: Obstetrics department of a university hospital. POPULATION AND DESIGN: This prospective study includes women with fetal growth restriction and abnormal umbilical artery Doppler results, seen between November 2009 and January 2011. METHODS: 31 women were divided into two groups according to the aortic isthmus blood flow pattern just before birth: anterograde (n = 12) or retrograde (n = 19). MAIN OUTCOME MEASURE: Longitudinal measurements of fetal aortic isthmus in relation to perinatal outcome. RESULTS: Total morbidity and mortality rates were significantly higher in the retrograde flow group. There was no statistically significant difference for respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia or necrotizing enterocolitis, but the neonatal sepsis rate was significantly higher in the retrograde flow group. An abnormal aortic isthmus flow pattern was detected approximately 15-20 days after umbilical artery and middle cerebral artery Doppler flow abnormalities and 3-7 days before deterioration in ductus venosus blood flow. CONCLUSION: We suggest that aortic isthmus Doppler measurements are useful for identifying fetal growth restriction before deterioration in ductus venosus blood flow and fetal acidosis.

Role of 3D power Doppler sonography in early prenatal diagnosis of Galen vein aneurysm.

Vein of Galen aneurysm malformation (VGAM) is a rare congenital vascular anomaly. Although the cause of VGAM remains to be elucidated, the current hypothesis is persistence of the embryonic vascular supply, which leads to progressive enlargement and formation of the aneurysmal component of a typical VGAM. Here, we present a 36-year-old woman at 23 weeks' gestation (gravida 3, para 2) who was evaluated using 3D power Doppler sonography for the prenatal diagnosis of a vein of Galen aneurysm. Investigation using 3D power Doppler sonography allowed for a non-invasive yet diffuse and detailed prenatal assessment of VGAM. Thus, we suggest that prenatal sonography with 3D power Doppler may be an option in cases of VGAM.

Rubella vaccination during the preconception period or in pregnancy and perinatal and fetal outcomes.

The rubella vaccine is contraindicated in pregnancy. Between July and August 2009, the Turkish Republic Ministry of Health implemented a vaccine program to eradicate rubella in women in the reproductive period. In this program, many pregnant women were also vaccinated inadvertently. In this study, 62 pregnant women applied to our clinic who were vaccinated either during pregnancy or within one month before the last menstrual period. Seventeen of them were followed until the end of the pregnancy by fetal echocardiography and detailed ultrasonography. Rubella immunoglobulin (Ig) M and IgG antibodies were studied in the cord blood obtained at birth. All fetuses were examined by a pediatrician, an ophthalmologist and a pediatric cardiologist. A hearing test was also performed on all neonates. No signs of congenital rubella syndrome could be found.

Mid-trimester hyperechogenic bowel in a fetus of Turkish origin carrying a rarely seen mutation of cystic fibrosis.

Cystic fibrosis (CF) is one of the most common severe autosomal recessive genetic disorders, characterized primarily by chronic obstructive lung disease and maldigestion disorder. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Here we present a case of a fetus with hyperechogenic bowel, in which compound heterozygosity was established for the mutations p.IIe1000fsX1001 and p.Asp110His subsequent to amniocentesis. The mutations were most likely disease-causing, and pregnancy was terminated.

High-output cardiac failure in a fetus with thanatophoric dysplasia associated with large placental chorioangioma: case report.

Placental chorioangioma is an angioma arising from chorionic tissue. Fetal thanatophoric dysplasia is a lethal skeletal dysplasia due to mutation of fibroblast growth factor receptor 3 gene. These two conditions are rare and their coexistence in a given fetus is even rarer. We present a case of a fetus with thanatophoric dysplasia having high-output cardiac failure due to a large placental chorioangioma.

Prenatal diagnosis of Cantrell pentalogy in first trimester screening: case report and review of literature.

Pentalogy of Cantrell is a heterogeneous and rare thoraco-abdominal wall closure defect with the estimated prevalence of 1/65.000 to 1/200.000 births. Supraumbilical midline wall defect (generally omphalocele), deficiency of the anterior diaphragm and diaphragmatic peritoneum, defect of the lower sternum and several intracardiac defects are the components of Cantrell pentalogy. Etiology is unknown but a defect on the lateral mesoderm during the early stage of pregnancy is the most accepted hypothesis. Nowadays both 2- dimensional (2D) and 3-dimensional (3D) sonography are commonly used in diagnosis. In our case, a fetus with 11 weeks of gestation was reported as Cantrell pentalogy during first trimester screening. Additionally, unilateral limb defect and lumbar lordoscoliosis were detected through 3D sonography. Pregnancy was terminated according to parental desire. Karyotype was 46 XY. Early diagnosis is feasible in the first trimester if ectopia cordis and omphalocele exist. Additionally, development in ultrasound technology provides us with better visualization and early diagnosis. Prognosis seems to be poor in patients with complete Cantrell syndrome and patients with associated anomalies. Termination is the choice of treatment. Early diagnosis gives us a chance to reduce maternal morbidity and mortality related to termination.

The role of umbilical cord thickness and HbA1c levels for the prediction of fetal macrosomia in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to investigate the effects of HbA1c levels and umbilical cord thickness upon birth weight, particularly in pregestational and gestational diabetic patients. METHOD: Pregnant women were included in the study and were divided into two groups. The first group consisted of patients who were diagnosed with pregestational or gestational diabetes mellitus. The control group consisted of pregnant women who were not diagnosed with pregestational or gestational diabetes mellitus. Ultrasound examination was performed twice. Examinations were performed at 27-28 weeks and 36-37 weeks of gestation, respectively. During ultrasound examinations, fetal anthropometric parameters, biparietal diameter, abdominal circumference, femur length and estimated fetal weight (which was calculated automatically according to Hadlock's formula) were measured. Additionally, the sonographic cross-sectional areas of the umbilical cord, the umbilical arteries and the umbilical vein were measured in a free loop of the umbilical cord, using the software of the ultrasound machine. The cross-sectional area of Wharton's jelly was computed by subtracting the cross-sectional area of the vessels from that of the umbilical cord. HbA1c levels were measured for diabetic patients. RESULTS: At 27-28 gestational weeks, umbilical cord area and Wharton's jelly values were found to be statistically different in macrosomic fetuses compared with non-macrosomic fetuses for both groups (for cord area, P = 0.012; for Wharton's jelly, P = 0.001). Additionally, umbilical cord diameter vein and artery values were not statistically different between the two groups when macrosomic fetuses were compared with non-macrosomic fetuses. At 36-37 gestational weeks, when the relationship between umbilical cord components and birth weight was examined, there was a statistically significant difference when comparing macrosomic fetuses with non-macrosomic fetuses. There was a statistically significant correlation between umbilical cord area, umbilical cord diameter and fetal weight estimation at 36-37 gestational weeks. HbA1c values and fetal macrosomia did not show a statistically significant relationship (P = 0.701). CONCLUSION: A significant relationship between umbilical cord components and birth weight was not specific for the diabetic group. There was a significant relationship between birth weight and umbilical cord components for the control group as well. If the estimated fetal weight is combined with umbilical cord components, macrosomic fetuses can be predicted with more accuracy.

Comparison of the effects of new and conventional hormone replacement therapies on left ventricular diastolic function in healthy postmenopausal women: a Doppler and ultrasonic backscatter study.

We aimed to compare the effects of new treatment modalities to conventional hormone replacement therapy (HRT) on left ventricular (LV) diastolic function, by means of conventional and tissue Doppler echocardiography and the myocardial integrated backscatter (IBS) in postmenopausal women. One hundred and fifty healthy postmenopausal women were included in this study. Subjects were assigned to one of the five groups receiving 1 year of treatment (estrogen, estrogen plus progesterone, raloxifene, tibolone or placebo). E and A wave velocity, E/A ratio, isovolumic relaxation time (IVRT), deceleration time (DT), peak early (Em) diastolic mitral annular velocity, E/Em ratio, the cyclic variation of integrated backscatter (CVIBS) and the mean value of the IBS signal (MIBS) were determined before and 12 months after therapy. E (76 +/- 10 vs. 98 +/- 8 cm/s, P = 0.0001 and 78 +/- 10 vs. 90 +/- 12 cm/s, P = 0.02, respectively), Em (14.3 +/- 2.4 vs. 16.4 +/- 2.5 cm/s, P = 0.001 and 15.1 +/- 3.4 vs. 16.2 +/- 3.5 cm/s, P = 0.01, respectively), and E/A ratio (1.15 +/- 0.3 vs. 1.42 +/- 0.4, P = 0.0001 and 1.0 +/- 0.2 vs. 1.22 +/- 0.2, P = 0.01, respectively) were increased significantly compared to pretreatment in both estrogen and raloxifene groups while DT, A, E/Em, and IVRT were significantly decreased. A significant increase in CVIBS and decrease in MIBS were detected 12 months after estrogen and raloxifene administration while no significant changes were observed in other groups. Changes in the MIBS and CVIBS were found to be independently associated with the observed changes in the diastolic function indexes during therapy. Both estrogen and raloxifene regimens may improve LV diastolic functions in healthy postmenopausal women. This improvement may be a result of direct cardiac effects on LV myocardium.

The immunohistochemical evaluation of VEGF in placenta biopsies of pregnancies complicated by preeclampsia.

OBJECTIVE: The study was designed to determine the protein levels of vascular endothelial growth factor (VEGF) in the placenta biopsies of patients with preeclampsia and compare with normal controls. DESIGN: Prospective cohort study. METHODS: The placental biopsies were obtained from ten patients with preeclampsia and ten patients of control group at the time of delivery. Avidin-biotin-peroxidase immunohistochemistry was then performed to identify levels of VEGF protein within the tissue and a semi-quantitative method was devised to score the amount of staining present in the sample. Two histopathologists who were blinded to the groups were asked to score each sample for the intensity of staining and the number of cells stained in a randomly selected per high-power fields of each sample. The resulting "H-score" was computed as a product of intensity and percent of cells stained. RESULTS: The VEGF expression was significantly higher in placenta biopsies of preeclamptic patients compared to that of controls (271.2 +/- 22.65 vs. 201.9 +/- 12.33, P = 0.000). CONCLUSION: Immunostaining of VEGF is significantly higher in placenta biopsies of patients with preeclampsia.