Evaluation of Inferior and Superior Vena Cava and the Vena Cava Ratio in Growth Restricted Fetuses.

OBJECTIVE: To evaluate the changes in the diameters of superior vena cava (SVC) and inferior vena cava (IVC) and to measure the ratio between SVC and IVC in growth-restricted fetuses and compare these results with normally grown fetuses. METHODS: Twenty-three consecutive patients with fetal growth restriction (FGR) (Group I) and 23 pregnant gestational age-matched controls (Group II) between 24 and 37 weeks of gestation were enrolled in the study between January 2018 and October 2018. The diameter of the SVC and IVC from inner wall to inner wall was measured in all patients by sonographic examination. The ratio between the diameter of the SVC and IVC was also measured in each patient to eliminate the gestational age factor. We have named this ratio the "vena cava ratio" (VCR). All parameters were compared between the two groups. RESULTS: The diameter of the SVC was significantly greater in the fetuses with FGR (2.6-7.7 [5.4]) than in controls (3.2-5.6 [4.1]; P = .002; P < .01). The diameter of the IVC was significantly less in the fetuses with FGR (1.6-4.5 [3.2]) than in controls (2.7-5 [3.7]; P = .035; P < .05). The VCR was between 1.1 and 2.3 and the median value was 1.8 in Group I. The VCR was between 0.8 and 1.7 and the median value was 1.2. VCR was significantly higher in fetuses with FGR (P = .001 P < .01). CONCLUSION: This study shows that VCR is higher in fetuses with growth restriction. Further studies are needed to clarify the association between VCR and antenatal prognosis and postnatal results.

Relationship between second-trimester amniotic fluid and plasma levels of angiopoietin-2 and thrombomodulin with adverse pregnancy outcome.

Our objective is to investigate maternal midtrimester plasma and amniotic fluid (AF) levels of angiopoietin-2 (Ang-2) and thrombomodulin (TM), which are involved in vascular remodelling and endothelium activation, in placental disorders including foetal growth restriction (FGR) and preeclampsia (PE). This prospective multiparametric pilot study was conducted at the Perinatology Division of Trakya University in a population undergoing genetic amniocentesis. Both AF and plasma aliquots were kept in -80 °C until ELISA assay. The pregnancies were followed up until the end of gestation in terms of obstetric results. Amniotic fluid and plasma aliquots from 127 pregnancies who underwent genetic amniocentesis between 16 and 24 weeks of gestation were analysed. During the final data evaluation, 39 were excluded with various reasons. Twelve subsequently developed FGR and 11 complicated with PE. The control group (n = 65) was consisted of women delivered >37th week with an uncomplicated outcome. The midtrimester maternal Ang-2 levels in both AF and plasma and also TM levels in plasma were found to be significantly increased in pregnancies who subsequently developed FGR or PE (p< .05). The midtrimester Ang-2, which rises in both plasma and AF and the midtrimester TM, which only significantly increase in plasma compartment in PE group, as compensatory mechanism may be the precursors of placental disorders including FGR and PE.Impact StatementWhat is already known on this subject? It is known that angiopoietin-2 (Ang-2) has important role in placental angiogenesis and vascular remodelling. TM which is a receptor for Ang-2 plays a protective role in pregnancy by preventing the uteroplacental circulation from thrombosis.What do the results of this study add? The present study demonstrates that both midtrimester maternal plasma Ang-2/TM and amniotic fluid (AF) Ang-2 levels were significantly higher in PE and FGR group than uncomplicated group. Midtrimester AF TM levels were not significantly higher in PE group than the control group.What the implications are of these findings for clinical practice and/or further research? In the clinical practice, high levels of midtrimester Ang-2 and TM in plasma may be used for the prediction of FGR and PE. Although amniocentesis is not practical in the clinical use, the levels of these two markers in both AF and plasma compartments may contribute to explain the pathophysiology of FGR and PE.

Prenatal diagnosis of 20p13 microdeletion syndrome.

OBJECTIVE: The objective of this study was to report the first case of prenatal diagnosis of the fetal 20p13 microdeletion syndrome in the literature. CASE REPORT: The mother was 31 years old and had a first trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 23 weeks of gestation showed mild ventriculomegaly (10.2 mm) and absent septum pellucidum. She underwent amniocentesis because of the abnormal imaging results. Karyotype analysis revealed normal results. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the fetus and parents. CMA detected 317.902 kb deletion of 20p13 in fetus. Finally, pregnancy was terminated at 32 weeks of gestation. CONCLUSION: This study is the first to report the prenatal diagnosis of a 20p13 microdeletion syndrome. Our results further confirmed that genes in this region, including SOX12, NRSN2 are essential for normal fetal growth and TBC1D20 for normal brain development.

Comparison of the efficacy of the immediate-release and osmotic push-pull system formulations of nifedipine for tocolysis.

AIM: To compare the immediate-release (IR) and osmotic push-pull system formulations of nifedipine used for tocolysis in prolonging pregnancy, neonatal outcomes and maternal-fetal adverse effects. METHODS: We evaluated 140 pregnant women who received the IR (n = 72) and osmotic push-pull system (n = 68) formulations of nifedipine for tocolysis due to threatened preterm labor between 240/7 and 336/7 weeks of gestation. Groups were compared in terms of efficacy of tocolysis in prolonging pregnancy for more than 48 h, 7 days and up to 37 weeks of gestation, total number of days gained for prolonging pregnancy, delivery weeks, maternal-fetal adverse effects and neonatal outcomes including ventilation support, need for intubation or surfactant, intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, admission to neonatal intensive care unit, neonatal death, Apgar scores at the 1st and 5th minutes. RESULTS: There was no significant difference between the two groups in prolonging pregnancy for more than 48 h or 7 days, total number of days gained after tocolysis initiation, delivery weeks, the number of births at 340/7 -366/7 weeks or after 37 weeks of gestation (P > 0.05). Maternal-fetal adverse effects and neonatal outcomes were similar in both groups (P > 0.05). CONCLUSION: The efficacy of IR and osmotic push-pull system formulations of nifedipine have similar effects in terms of tocolysis and neonatal outcomes, adverse effects. Osmotic push-pull system formulation of nifedipine may be an alternative medication in tocolytic therapy due to its ease of use and the absence of loading dose necessity.

Placental and serum levels of human Klotho in severe preeclampsia: A potential sensitive biomarker.

INTRODUCTION: The Klotho (KL) gene, initially defined as an anti-aging gene in mice, shares 86% of the amino acid sequence withthe human KL protein. The KL gene plays roles in endothelial nitric oxide production, angiogenesis, antioxidant enzyme production and protecting against endothelial dysfunction, all of which may be associated with preeclampsia (PE). Human KL is the precursor of the gene products: α-KL and ß-KL. In this study, we evaluated the gene expression, serum and placental levels of human KL in women with severe PE, pregnant women with chronic hypertension and healthy pregnant controls. Also, the gene expression, serum and placental levels of human decorin (DCN) were evaluated. METHODS: A total of 36 patients with severe PE, 10 with chronic hypertension, and 28 with healthy controls were enrolled. Placental and serum levels together with of KL and DCN were measured by ELISA and alsogene expression of these were evaluated. RESULTS: Placental and serum KL levels were significantly higher in the PE than in the controls and in women with chronic hypertension. Serum DCN levels were significantly higher in the PE women compared to controls and pregnant women with chronic hypertension. Placental DCN was similar in PE and healthy controls. There was no significant difference in the gene expression of KL and DCN in the groups. The best cut-off level for human KL to identify the presence of PE was calculated as 12.48 pg/ml with a sensitivity of 100% and and specificity of 96%, whereas for DCN 62.33 ng/ml to assess the presence of PE with a sensitivity of 86.1% and a specificity of 88%. CONCLUSION: Human KL may be a valuable marker for PE, with high sensitivity and specificity. It also appears to be more sensitive and specific than human DCN.

Does emergency cerclage really works in patients with advanced cervical dilatation?

OBJECTIVE: To asses the efectivity of emergency cerclage in the patients with advance cervical dilatation and prolapsed membranes. MATERIAL METHODS: The patients who have ≥4 cm cervical dilatation with protruding membranes were included in the study. The patients were divided into two groups. Group I was consisted of the patients who had emergency cerclage procedure and group II was consisted of the patients who denied the operation and expectantly managed. The physical examination, pregnancy outcomes and the complications were compared between the groups. The results of the patients with emergency cerclage were analysed. RESULTS: 21 patients were referred with a ≥4 cm cervical dilatation with protruding membranes 33.3% of women with emergency cerclage were delivered within one week from the admission. One patient, who was a grand multiparous (G6P4A1), was delivered a healthy infant at 40 weeks of gestation. The remaining five patients were delivered between 21 and 24 weeks, but all the infants were died due to extreme prematurity.Two patients (22.2%) developed chorioamnionitis that necessitated long hospitalization (14-21 days). In group II (expectant management) 83,3% of the patients were delivered within the 48 h from the admission. There were no case of chorioamnionitis in group II. CONCLUSION: Emergency cervical cerclage is not a rationale option for the patients with an advanced cervical dilation (>4 cm) together with protruding membranes in early second trimester because of the short prolongation time and high complication rate.

Emergency cerclage in twins during mid gestation may have favorable outcomes: Results of a retrospective cohort.

PURPOSE: Cervical cerclage treatment for cervical changes at mid trimester is a very controversial topic in twins. The aim of the study was to present our maternal and fetal outcomes of mid-trimester cervical cerclage in twin pregnancies. BASIC PROCEDURES: This study was performed using data extracted from the medical files of the twin pregnancies whom performed emergency cervical cerclage between January 2012 and March 2018 at Trakya University, Facuty of Medicine, Department of Perinatology. MAIN FINDINGS: Mean (min.-max.) gestational age at delivery was [27.3 (21-34) weeks]. The median time between cervical cerclage and delivery was 6.4 weeks, while the maximum prolongation of the pregnancy was 11 weeks. The median prolongation period of pregnancy was 4.1 weeks in patients with bulging membranes, but 10 weeks in patients with cervical effacement and cervical shortening. Eight infants died at the neonatal period. Two patients (20%) developed late abortions at 21 and 22 weeks of gestation, and 2 women (20%) delivered extremely premature neonates at the 24th weeks. Overall neonatal mortality rate was 40% (8/20 neonates). Twelve out of twenty were born alive (60%). PRINCIPAL CONCLUSIONS: Despite the lack of randomized controlled trials, it seems reasonable to offer emergency cervical cerclage to twin pregnancies with cervical shortening (<15mm). For the twin pregnancies with advanced cervical dilatation and protruding membranes, emergency cervical cerclage should be an option only for carefully selected patients after informing about the complications and low success rate.

Comparison of postpartum sonographic findings after uneventful vaginal and cesarean section deliveries.

Objective: To prospectively determine the sonographic findings of the postpartum uterus 24 hours after vaginal delivery and cesarean section. Methods: Women who had uneventful vaginal delivery or cesarean section from July 2015 to May 2018 in a tertiary care hospital were prospectively included. Uterine lengths, endometrium, amout of free fluid, the distance between the uterine fundus-promontorium and uterine fundus-L5 were evaluated 24 hours after delivery. Results: The mean (min-max) endometrial thickness in the vaginal delivery and cesarean section groups were 13.3 (4-25) and 12.4 (4-29) mm, respectively. Fundus-cervix length was significantly higher in the vaginal delivery group compared to the cesarean section group (184.05 ± 16.8 vs 163.6 ± 6.7 mm, p <0.001). The measurements of anterior and anterior-posterior walls of the uterus, anteroposterior uterine length and uterine width were similar in both groups. Promontorium-fundus length was significantly higher in patients who delivered vaginally than those by cesarean section (123.3 ± 13.6 vs 108.7 ± 23.3 mm, p = 0.005). Conclusion: The measurement of L5-fundus distance is a simple and effective technique to evaluate the size of the uterus. Homogenous endometrium up to 30 mm in asymptomatic patients may be a normal finding 24 hours after delivery. The results of this study may be helpful in the decision-making process in cases of early postpartum hemorrhage or hemodynamic instability.Objective: To prospectively determine the sonographic findings of the postpartum uterus 24 hours after vaginal delivery and cesarean section. Methods: Women who had uneventful vaginal delivery or cesarean section from July 2015 to May 2018 in a tertiary care hospital were prospectively included. Uterine lengths, endometrium, amout of free fluid, the distance between the uterine fundus-promontorium and uterine fundus-L5 were evaluated 24 hours after delivery. Results: The mean (min­max) endometrial thickness in the vaginal delivery and cesarean section groups were 13.3 (4­25) and 12.4 (4­29) mm, respectively. Fundus-cervix length was significantly higher in the vaginal delivery group compared to the cesarean section group (184.05 ± 16.8 vs 163.6 ± 6.7 mm, p <0.001). The measurements of anterior and anterior-posterior walls of the uterus, anteroposterior uterine length and uterine width were similar in both groups. Promontorium-fundus length was significantly higher in patients who delivered vaginally than those by cesarean section (123.3 ± 13.6 vs 108.7 ± 23.3 mm, p = 0.005). Conclusion: The measurement of L5-fundus distance is a simple and effective technique to evaluate the size of the uterus. Homogenous endometrium up to 30 mm in asymptomatic patients may be a normal finding 24 hours after delivery. The results of this study may be helpful in the decision-making process in cases of early postpartum hemorrhage or hemodynamic instability.

VEGFR-1, Bcl-2, and HO-1 Ratios in Pregnant Women With Hypertension.

BACKGOUND/AIM: Preeclampsia (PE) is a multisystem disease resulting in high maternal-fetal morbidity and mortality. The aim of the study was to investigate antiangiogenesis-associated alterations in antiapoptotic and antioxidative proteins in PE. METHOD: Of the 46 patients with PE, 25 (54.3%) were with gestational hypertension (GH), 12 (26%) were with mild, and 9 (19.5%) were with severe PE. The serum levels of vascular endothelial growth factor receptor 1 (VEGFR-1), heme oxygenase 1 (HO-1), and B-cell lymphoma/leukemia (Bcl-2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: In the severe PE group, the VEGFR-1 serum levels (27.3 ± 16.8 vs 13.3 ± 10.7 ng/mL, P = .023) were higher, but the Bcl-2 levels (1.5 ± 0.2 vs 2.1 ± 1.7 ng/mL, P = .047) were lower than the levels in the GH-mild PE group (P = .047). Also, VEGFR-1/Bcl-2 ratio in the severe PE group was significantly higher (P = .003) than the ratio in the GH-mild PE group. CONCLUSION: The Bcl-2 and HO-1 proteins seem to have important roles in the antiangiogenic environment of preeclampsia.

Carotid intima-media thickness: a new marker of patients with uterine leiomyoma.

OBJECTIVE: To determine whether or not there are any significant differences in carotid intima-media thickness between patients with uterine leiomyoma and controls. STUDY DESIGN: Patients whose ages were between 40 and 50 years, with body mass index <30kg/m(2), and with a pathological diagnosis of uterine leiomyoma constituted the study group. Control subjects had no uterine leiomyoma proven by sonography. Demographic, clinical, and drug history data were collected. Right, left and mean carotid intima-media thickness measurements were obtained by ultrasonography. RESULTS: Carotid intima-media thickness and serum high-density lipoprotein (HDL) levels were significantly different between the groups (p=0.0001 and p=0.001 respectively), being respectively higher and lower in the leiomyoma group than in controls. Stepwise binary logistic regression analysis revealed that uterine leiomyoma development ratio was 159.32 times higher when carotid intima-media thickness was over 0.61mm (p=0.0001). In patients with uterine leiomyoma, carotid intima-media thickness was significantly less in patients taking statins compared to those not on these drugs (p=0.0001). CONCLUSION: The present study demonstrated a positive association between carotid intima-media thickness and the presence of uterine leiomyoma. Conversely, an inverse association was suggested between HDL and uterine leiomyoma. These findings suggest that women with uterine leiomyoma might have an increased risk of subclinical atherosclerosis.

Assessment of CA-125 area under the curve as a prognostic factor in patients with ovarian cancer.

The goal of this study was to evaluate the efficacy of CA-125 area under the curve (CA-125 AUC) as a prognostic factor following surgical treatment for ovarian cancer patients. A retrospective analysis was conducted on ninety-five patients with ovarian cancer who had primary treatment in a tertiary center between 2000 and 2010. After either optimal or cytoreductive surgery, all patients underwent adjuvant chemotherapy. CA-125 AUC was calculated for each patient that had a minimum of three CA-125 serum measurements during the treatment period. The mean age at diagnosis and mean survival were 53.9 years (range, 16-75 years) and 35.6 ± 22.9 months (range, 3.1-95.4 months), respectively. The mean (and median) CA-125 AUC of patients of FIGO stages I, II, III, and IV was 53.0 (42.5), 58.06 (58.06), 97.8 (54.6), and 405.2 (149.3) IU/ml day, respectively (p = 0.004). The mean CA-125 AUC was 57.7, 410.1, and 636.3 IU/ml day for patients with a complete response, partial response, and no response/progressive disease to first-line chemotherapy, respectively (p < 0.001). The CA-125 AUC cut-off level for an overall survival of ≥5 years was 99.75 IU/ml day with a sensitivity of 90.9 % (95 % CI, 70.8-98.6) with 1.27 as positive likelihood ratio. Patients who suffer from ovarian cancer, with a lower CA125 AUC, have a better overall survival than those with a higher CA125 AUC. CA-125 AUC could be used as an independent factor for evaluating the treatment efficacy and chemotherapy response.

Evaluation of cardiovascular risk factors in women with uterine leimyoma: is there a link with atherosclerosis?

OBJECTIVE: Both uterine leimyoma (UL) and cardiovascular disease are public health problems affecting women at different age ranges. Smoking, obesity, and hypertension have been shown to be associated with UL in different random studies. However cardiovascular risk factors have not been evaluated systematically in patients with UL. Accordingly, we aimed to evaluate the cardiovascular risk factors and their relation with the presence of UL. MATERIAL AND METHODS: One hundred and eighty nine patients with the pathological diagnosis of UL and one hundred and eighty nine age matched control subjects without UL were retrospectively included in the study from our data base of the pathology and gynecology departments. Controls were patients with intact uteri who had visited the same physicians for a routine checkup that included a pelvic examination and uterine sonogram and without mention of physical findings consistent with UL. The following clinical and demographic parameters were recorded; age, sex, hypertension, diabetes mellitus, and hypercholesterolemia. Current cigarette smoking was defined as active smoking within the past 12 months. RESULTS: Comparison of cardiovascular risk factors between with and without UL revealed that the presence of hypertension (80 (42.3%) vs 53 (28%) p=0.004) diabetes mellitus (33 (17.4%) vs. 16 (8.4%) p=0.009), smoking (31 (16.4%) vs. 11 (5.8%) p=0.001), were significantly higher in patients with UL than in control subjects. The mean-age and presence of hyperlipidemia were comparable between the two groups. Logistic regression analysis revealed an independent and positive association of UL with the presence of hypertension (odds ratio 2.02 CI: 1.25-3.27 p=0.004), diabetes mellitus (odds ratio 2.43 CI: 1.23-4.79 p=0.010), and smoking status (odds ratio 3.46 CI: 1.65-7.22 p=0.001). CONCLUSION: We have shown that major cardiovascular risk factors namely, hypertension, diabetes mellitus and smoking are significantly and independently associated with UL. Our findings highlight the possible association of UL with atherosclerosis.

The investigation of tumoral angiogenesis with HIF-1 alpha and microvessel density in women with endometrium cancer.

OBJECTIVE: Hypoxia inducible factor 1 alpha (HIF-1α) is a nuclear protein upregulated in response to reduced cellular oxygen concentration which therefore acts as a marker for hypoxia. The aim of this study was to determine tumoral angiogenesis with immunohistochemical markers in endometrium cancer and its relation with stage, grade, survival rates and other prognostic factors. MATERIAL AND METHODS: Using the database in our Gynecologic Oncology clinic, we selected 94 patients who were diagnosed with endometrial cancer and underwent primary surgery at our institution between 2001 and 2010. Tissue microarrays believed to demonstrate the optimum part of the tumor were reprepared from the paraffin blocks. Angiogenesis and microvessel density (MVD) were investigated with the aid of HIF-1α and CD34 antibodies. RESULTS: High expression of HIF-1α was significantly more frequent in advanced grade endometrial cancers (p=0.044). HIF-1α expression was highly correlated with CD34 expression in the tumor cells (p<0.001). However lack of relation among stage, overall survival rates and histological types were analyzed with HIF-1α. When we compared HIF-1α positive and negative cases with cervical, adnexial, lymphovascular and myometrial invasion, there was no difference between these groups. MVD was evaluated with CD34 and it was remarkable and significantly different on advanced grade tumors (r=0.268; p=0.009). A similar significant difference was observed between the high expression of CD34 and type II endometrial cancer histology (p<0.001). However, there was no relationship between the MVD and stage or survival rates. CONCLUSION: High expression of HIF-1α is associated with tumoral angiogenesis in endometrial adenocarcinomas. Further studies targeting HIF-1α for disrupting mechanisms essential for tumor growth in endometrium cancer will be significant investigations in the future.

The assessment of nuchal translucency and serum markers for down syndrome screening with ductus venosus Doppler measurements in the first trimester.

OBJECTIVE: The aim of the study was to improve nuchal translucency (NT) and serum marker Down syndrome (Tri21) screening methods by including fetal ductus venosus (DV) Doppler measurements. MATERIAL AND METHODS: A total of 213 pregnant women were screened consecutively by combining maternal age, fetal NT and maternal serum pregnancy associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotropin (f ß-HCG) values at 11-14 weeks of gestation. Also, a DV Doppler analysis was performed for the contribution to the screening for Tri21 and other fetal anomalies or adverse pregnancy outcomes. RESULTS: Twelve fetuses had DV PI measurements above the 95th percentile and two (17%) developed intrauterine growth retardation. DV PI values negatively correlated with birth weight (p=0.013, r=0.171). Two patients had T 21 among the study group (0.9%) with abnormal biochemical screening results. In these with Tri21, the combined test risk was above the suggested limit (>1/250). PAPP-A was <0.4 MoM in 23, and f ß-HCG was >1.91 MoM in 49 patients. The rates of false positivity were 10% for PAPP-A and 22% for f ß-HCG. The sensitivity, specificity, positive and negative predictive values of the combined test was 100%, 95%, 20% and 100%, respectively. CONCLUSION: The combined test has high sensitivity and specificity for Tri21 detection. The addition of DV Doppler ultrasound in the first trimester might have the advantage of predicting some adverse pregnancy outcomes. However, in the Turkish population, further studies with larger numbers of patients will be needed to establish the usefulness of DV for the detection of Tri21 or the prediction of some major cardiac anomalies.