Cem Yaşar Sanhal

Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study

To evaluate the relationship between idiopathic recurrent pregnancy loss (RPL) and oxidative stress (OS) by means of thiol/disulfide homeostasis via a novel technique.

Assessment of fetal myocardial performance index in women with pregestational and gestational diabetes mellitus.

Fetal cardiac left ventricular function in pregnant women with pregestational or gestational diabetes mellitus was investigated by exploring fetal myocardial performance index (MPI) and E wave/A wave peak velocity (E/A) ratio.

Conservative management of placenta previa percreta by leaving placental tissue in situ with arterial ligation and adjuvant methotrexate therapy

Placenta percreta is one of the life-threatening conditions in modern obstetrics. The rising caesarean section rate means rising placenta percreta rate. Treatment strategies range from a caesarean hysterectomy to leaving the placenta in situ with or without internal iliac artery ligation/uterine artery embolisation and/or methotrexate therapy. We describe a case of placenta previa percreta which we managed successfully with conservative modalities.

Glucocorticoid effects on angiogenesis are associated with mTOR pathway activity

Glucocorticoids (GC) often are administered during pregnancy, but despite their widespread use in clinical practice, it remains uncertain how GC exposure affects pro-angiogenic factors and their receptors. We investigated the effects of GC on vascular endothelial growth factor (VEGF), placental growth factor (PIGF), vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) protein and mRNA expressions and investigated the possible association of GC with the Akt/mTOR pathway. We incubated human umbilical vein endothelial cells (HUVECs) with a synthetic GC, triamcinolone acetonide (TA). TA administration caused decreased cellular and soluble VEGF and VEGFR1 protein expressions and increased soluble VEGFR2 expression. VEGF, VEGFR1 and VEGFR2 mRNA expressions were altered in a time and dose dependent manner. PIGF protein expression was unaffected by TA treatment, but PIGF mRNA expression decreased in a dose dependent manner after incubation for 48 and 72 h. Phospho-mTOR and phospho-Akt expressions were unaffected. Phospho-p70S6K and phospho-4EBP1 protein expressions and the vascular network forming capacity of HUVECs decreased in a dose dependent manner. We found that GC exert detrimental effects on angiogenesis by altering cellular and soluble angiogenic protein and mRNA levels, and vascular network forming capacities by the Akt/mTOR pathway.

Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma

It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Thiol/disulphide homeostasis in pregnant women with Familial Mediterranean fever

Objective: To investigate the presence of oxidative stress (OS) in pregnant women with Familial Mediterranean fever (FMF) in the first trimester by evaluating thiol/disulphide homeostasis. Study design: A total of 31 pregnant women with a diagnosis of FMF, between 110 and 136 weeks of gestation, were compared with 51 healthy pregnant controls at the same gestational weeks. A recently defined method was used to measure plasma native thiol, total thiol and disulphide levels. Results: There were no differences between groups in terms of maternal age, body mass index and numbers of gravida and parity. Antenatal complications (45.2% vs. 9.8%, P = 0.001) and primary caesarean section (22.6% vs. 5.9%, P = 0.037) were higher in the FMF group. Pregnant women with FMF had significantly lower first trimester serum levels of native thiol (297.5 μmol/l (153.2–441.8) vs. 366.1 μmol/l (288.7–432.4), P = 0.000), total thiol (327.2 μmol/l (171.0–471.0) vs. 389.9 μmol/l (317.1–449.8), P = 0.000) and higher levels of disulphide (14.2 ± 4.5 μmol/l vs. 12.4 ± 3.4 μmol/l, P = 0.045). No differences were found in these parameters among FMF patients with and without antenatal complications. Conclusions: The main outcome demonstrates a relation between OS and pregnant women with FMF in the first trimester of gestation. OS in the first trimester may be a major aetiological factor of unfavourable pregancy outcomes in this group of patients.

Associated anomalies with neural tube defects in fetal autopsies

Abstract Neural tube defects (NTD), the consequences of aberrant neural tube closure during embryogenesis, have been mostly investigated in terms of their high prevalence, rate of mortalities and serious morbidities. A proper prenatal outcome counseling of couples coming across a fetal anomaly necessitates the detection and categorization of the primer abnormality, all the co-existing malformations. The aim of this work is to study the incidence and relevance of associated malformations in order to offer a complete pathology report with a true diagnosis. In this study, among 542 fetal autopsy 62 (%11.4) cases with NTD was recorded by the Akdeniz University Pathology Department between January 2006 and June 2012. Twenty (32.4%) NTD cases were associated with anomaly. Twelve cases of associated groups consisted of a congenital syndrome/association, spondylothoracic dysplasia, amniotic band syndrome, Meckel–Gruber syndrome, schisis association. The frequency of associated NTD was 32%, this result was higher than previous reports. NTDs have a significant genetic component to their etiology that interacts with environmental risk factors, which might pose Turkey to be a country with high prevalence of NTD. We want to emphasize that intensive screening, documentation of co-existent abnormalities of NTD, should be conducted in order to exhibit certain diagnosis, to perform proper prenatal genetic counseling of parents for on-going/future pregnancies.

A retrospective analysis of pregnancy outcomes after kidney transplantation in a single center.

Background: We reported pregnancy outcomes after kidney transplantation in a single transplant center. Methods: We reviewed the perinatal outcomes of female kidney transplant patients of reproductive age (18-40 years) from 1987 to 2011. Results: A total of 246 patients were reviewed. Of these, 43 women registered a pregnancy following kidney transplantation. The mean patient age was 31.3 ± 4.2 years (range 24-40). The mean transplant-conception interval was 35.9 ± 12.6 months (range 24-120); 9 patients had a cadaveric allograft. The human leukocyte antigen match was ≥3/6 for 34 patients. The rate of live births was 29/43 (67.4%), miscarriage 10/43 (23.2%), preterm delivery 7/29 (24.1%), preeclampsia 5/29 (17.2%), and intrauterine growth retardation 2/29 (6.9%). Overall, 3/29 patients (10.3%) received a blood transfusion during pregnancy due to persistent symptomatic anemia, despite iron replacement and erythropoietin therapy; 24 patients (82%) had a cesarean section delivery; 3 patients had kidney rejection during pregnancy, with 2 occurring during the 6th postpartum month. Conclusion: Pregnancy should be considered a high risk in renal transplant recipients, necessitating close follow-up.

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.

An alternative method for measuring oxidative stress in intrahepatic cholestasis of pregnancy: thiol/disulphide homeostasis

Abstract Purpose: The aim of our study was to evaluate the oxidative stress (OS) in pregnant women with intrahepatic cholestasis of pregnancy (ICP) by evaluating thiol/disulphide homeostasis using an alternative technique. Methods: A total of 57 pregnant women with ICP were compared with 50 gestational age and body mass index matched controls. A recently defined method was used for the measurement of plasma native-total thiol and disulphide levels. The independent two-sample t test, Mann–Whitney-U test, Chi-square test, binary logistic regression with backward elimination and receiver operating characteristic (ROC) curve was performed for statistical analyses. Results: Pregnant women with ICP (n = 57) versus controls (n = 50) had significantly lower serum levels of native thiol (233.8 ± 47.4 μmol/L vs. 308.5 ± 51.7 μmol/L, p < .001), total thiol (258.4 ± 46.5 μmol/L vs. 328.0 ± 52.0 μmol/L, p < .001) and higher levels of disulphide (12.3 ± 3.6 μmol/L vs. 9.7 ± 3.4 μmol/L, p < .001). Binary logistic regression showed that the most important variables related to ICP were native thiol and total thiol. According to the ROC curve, the optimal cut-off level for native thiol was 280.0 μmol/L (sensitivity: 86%, specificity: 84.2%, area under the curve (AUC):0.896, 95% CI: 0.831–0.962, p < .001), and the optimal cut-off level for total thiol was 300.0 μmol/L (sensitivity: 86%, specificity: 80.7%, AUC: 0.883, 95% CI: 0.815–0.951, p < .001). Conclusions: To our knowledge, this is the first study in the literature exploring thiol/disulphide balance in ICP. We found that thiol/disulphide balance indicate OS in pregnant woman with ICP.