The role of ERK-1 and ERK-2 gene polymorphisms in PCOS pathogenesis.

BACKGROUND: Ovulation is regulated by extracellular signal-regulated kinase-1 (ERK-1) and ERK-2 signaling mechanisms, and ERK-1/2 kinases modulates the function of most of the LH-regulated genes. Defective ERK kinase signaling that is secondary to a genetic problem contributes to both ovulatory dysfunction and metabolic problems in polycystic ovary syndrome (PCOS). We planned to investigate ERK-1 and ERK-2 gene polymorphisms in PCOS for the first time in the Turkish population. METHODS: One hundred two PCOS patients and 102 healthy controls were recruited for this patient control study. HOMA-IR, Ferriman-Gallwey score (FGS), waist-to-hip ratio (WHR), and body mass index (BMI) were assessed. Lipid profile levels, CRP, and total testosterone were determined. ERK-2 rs2276008 (G > C) and ERK-1 rs11865228 (G > A) SNPs were analyzed with a real-time PCR system. RESULTS: ERK-1 and ERK-2 genotypes were found to differ between the PCOS and control groups. In patients with PCOS, ERK-1 GA and ERK-2 GC genotypes were different in terms of BMI, FGS, HOMA-IR, CRP, total testosterone, and total cholesterol levels. CONCLUSIONS: ERK-1 and ERK-2 genes are involved in PCOS pathogenesis. BMI, FGS, HOMA-IR, and CRP levels are related to the heterozygote polymorphic types of ERK-1 and ERK-2 genes.

The evaluation of maternal systemic thiol/disulphide homeostasis for the short-term prediction of preterm birth in women with threatened preterm labour: a pilot study.

The aim of this study was to investigate maternal systemic thiol/disulphide homeostasis (TDH) for the short-term prediction of preterm birth in women with threatened preterm labour (TPL). This prospective study included 75 pregnant women whose pregnancies were complicated by TPL. Thirty-seven of them delivered within 7 days and 38 of them delivered beyond 7 days. Maternal serum samples were collected at the day of diagnosis and the TDH was measured. The maternal disulphide level was significantly higher in pregnant women who delivered within 7 days (25.0 ± 9.8 µmol/L vs 19.4 ± 9.8 µmol/L, p: .015). The threshold value of 22.1 µmol/L for maternal disulphide level predicted delivery within 7 days with 62.2% sensitivity and 60.5% specificity (area under curve 0.651, confidence interval 0.53-0.78). The likelihood ratios for short cervix (≤25 mm) and maternal disulphide level (≥22 µmol/L) to predict delivery within 7 days was found to be 8.7 and 7.3, respectively. The likelihood ratio of combining two tests to predict delivery within 7 days was found to be 11.4. The maternal TDH, which is an indicator of oxidative stress status in maternal compartment, is disturbed in TPL cases who delivered within 7 days. Elevated maternal disulphide level along with cervical length screening predicts a short latency period in pregnancies with TPL. IMPACT STATEMENTWhat is already known on this subject? Spontaneous preterm delivery is one of the major complication of pregnancy and the common cause of neonatal morbidity and mortality. Threatened preterm labour (TPL) is also a frequent complaint in obstetric emergency care units in all around the world. Triaging women with TPL is mandatory for planning further management therapies, since the most of them will eventually deliver at term. Only the measurement of cervical length in symptomatic women has moderate accuracy in predicting preterm delivery. Short cervix is described as an independent predictor of preterm delivery in women with TPL, its predictive accuracy as a single measurement is relatively limited. On this account, several potential markers like foetal fibronectin in the cervicovaginal fluid, salivary oestriol, prolactin in vaginal discharge, maternal serum calponin and interleukin-6 in the amniotic fluid were examined to predict preterm delivery in previous studies. However, none of them represented an excessive predictive accuracy like high sensitivity, PPV or NPV.What do the results of this study add? We report a method which has higher diagnostic and predictive performance to identifying TPL women with high risk of preterm delivery. According to the current literature, there are accumulated data about the correlation between oxidative stress (OS) and preterm delivery regardless of the amniotic membrane status. However, it is still debated whether OS is a trigger or a consequence of preterm delivery. Our study provides evidence for the first time that maternal serum thiol/disulphide homeostasis, which is an indicator of OS in maternal compartment, is disturbed in TPL cases who delivered within 7 days. The high disulphide level in maternal serum, along with cervical length measurement (short cervix) accurately predicts a short latency period in TPL cases.What are the implications of these findings for clinical practice and/or further research? This novel test combination (maternal serum disulphide level and cervical length measurement) could be used clinically to triage pregnant women presenting with TPL, avoiding overtreatment, unnecessary hospitalisations and increased medical costs. The future research would be addressed on reducing maternal OS by using new antioxidant treatment strategies to improve perinatal and long-term childhood outcomes.

Comparison of topical lidocaine spray with forced coughing in pain relief during colposcopic biopsy procedure: a randomised trial.

Our objective was to compare the effectiveness of local lidocaine spray (LS) compared to forced coughing (FC) for relieving the pain during colposcopically guided cervical biopsies (CGBs). The study was a randomised study, which included patients with abnormal cervical cytologic results requiring a colposcopic biopsy procedure. The patients were randomly assigned to either the 10% LS or the FC groups before the biopsy procedure. As a primary outcome, the pain was assessed by using a 10 cm visual analogue scale at the different steps during the procedure. Forty-four and 42 patients had CGBs using LS and FC, respectively. The age, parity, body mass index, history of previous curettage and vaginal delivery, smoking status and the number of biopsies were similar in both groups. The mean ± SD pain scores after the cervical biopsy were 3.25 ± 1.4 and 4.4 ± 1.3 in the LS and FC groups, respectively (p< .05). The operative time was longer in the LS than in the FC group (7.6 ± 1.4 vs. 5.2 ± 0.8, p: .004). No complication or adverse effect was observed in both groups. The present study showed that LS use can be recommended for pain relief during colposcopically directed cervical biopsy procedure with a superiority to the FC in the terms of pain and absence of any adverse reactions. Impact Statement What is already known on this subject? A colposcopic-guided cervical biopsy is a painful procedure and different techniques have been proposed to relieve this pain with conflicting results. Studies have demonstrated that a forced coughing is a good and easy method for relieving pain with some disadvantages. Local lidocaine spray (LS) is another option for pain relief during the biopsy procedure. However, no randomised study has compared these two methods yet. What the results of this study add? The results from this randomised study suggest that LS has superiority in terms of pain relief during the colposcopic biopsy procedure and has no adverse reactions. What the implications are of these findings for clinical practice and/or further research? The evidence from different studies showed some conflicting results regarding the pain relief methods during the colposcopic biopsy procedure. The local LS can be used in this procedure in routine clinical practice. However, further studies with larger samples and comparison of different methods are needed.

Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of the Levonorgestrel-Releasing Intrauterine System.

AIM: To evaluate the efficacy and safety of levonorgestrel-releasing intrauterine system (LNG-IUS) in the long-term treatment of heavy menstrual blood loss in women unrelated to intrauterine pathology. METHODS: One hundred and six parous women aged 33-48 years with recurrent heavy menstrual bleeding (HMB) participated in this study. The women were followed up for 24 months and were assessed for intensity of bleeding both for pre- and post-insertion periods. An LNG-IUS was inserted in each patient within 7 days of the start of menstrual flow. The women were followed up at 1, 3, 6, 12, 18, and 24 months following the insertion of the intrauterine device. RESULTS: One hundred and two women completed the follow-up period and had a significant reduction in the amount of menstrual blood loss. The LNG-IUS was well tolerated by all women. Pre-treatment of the use of the LNG-IUS, endometrial biopsy patterns for irregular proliferative endometrium and for atypical simple hyperplasia were 34/106 (32.08%) and 61/106 (57.55%) respectively and after treatment no abnormal pathologic findings were determined (p < 0.001). CONCLUSION: Our findings indicate that the LNG-IUS is effective for significantly reducing the amount of menstrual blood loss in women with HMB.

Ovarian Torsion in the Normal Ovary: A Diagnostic Challenge in Postmenarchal Adolescent Girls in the Emergency Department.

BACKGROUND Ovarian torsion can be seen in the otherwise-normal ovary and is a challenging issue in the emergency department. The aims were (1) to evaluate and compare the surgically verified ovarian torsion cases in otherwise-normal ovaries and ovaries including a mass or cyst and (2) to investigate whether the normal-appearing ovaries on ultrasound examination affected the diagnosis of ovarian torsion or not. MATERIAL AND METHODS A retrospective cohort study design was used. The medical records of all postmenarchal adolescent girls with surgically verified ovarian torsion treated in a university hospital from 2010 to 2016 were reviewed. RESULTS Twenty-nine post-menarchal girls were identified. The subjects were divided into two groups. Eight girls (group 1) had ovarian torsion in a normal ovary, and twenty-one girls (group 2) had ovarian torsion including a mass or cyst. The median ages of group 1 and 2 were 13 and 14 years, respectively. Abdominal pain was the main presenting symptom for all cases in both groups. Doppler flow studies were abnormal in 6/9 (66.6%) in group 1 and 12/21 (57.1%) in group 2. The time from first admission to the operation was statistically longer in group 1 than in group 2 (34.5±24.3 hours vs. 19.5±9.2 hours, respectively; p=0.001). The longitudinal axis of uterine size was significantly shorter in group 1 than in group 2 (34.3±2.9 mm vs. 47.6±4.5 mm, respectively; p=0.001). CONCLUSIONS Ovarian torsion in adolescent girls can be seen within the otherwise-normal ovary. The normal-appearing ovaries on ultrasound in the emergency department may lead to delay in the diagnosis of ovarian torsion in adolescent girls.

Is Maternal Blood Procalcitonin Level a Reliable Predictor for Early Onset Neonatal Sepsis in Preterm Premature Rupture of Membranes?

BACKGROUND: This study is aimed at comparing the early diagnostic accuracy of maternal blood white blood cell (WBC) count, C-reactive protein (CRP) and procalcitonin in predicting early onset neonatal sepsis (EONS) among early preterm premature rupture of membrane (PPROM) pregnancies. METHODS: A total of 57 consecutive pregnancies, complicated with PPROM, between 24 and 34 gestational weeks were recruited to the study at Suleymaniye Maternity Education and Research Hospital, Istanbul, Turkey between January 2012 and January 2013. All patients were hospitalized and followed up with expectant management. Maternal blood WBC count, CRP and procalcitonin levels were measured in the first 12 h of membrane rupture. EONS was diagnosed using clinical and laboratory findings, and obstetric and neonatal outcomes were noted. RESULTS: The cutoff value for maternal blood CRP was ≥9.49 mg/dl. This value predicted EONS with 77.8% sensitivity, 80.0% specificity, 77.8% positive predictive value (PPV) and 80.0% negative predictive value (NPV). The cutoff value for maternal blood procalcitonin was 0.071 ng/ml. This value predicted EONS with 85.2% sensitivity, 86.7% specificity, 85.2% PPV and 86.7% NPV. CONCLUSION: Maternal blood procalcitonin levels were superior to maternal blood CRP and WBC count in predicting EONS. Consequently, the maternal blood procalcitonin level is a clinically useful, non-invasive and reliable biomarker in antenatal prediction of EONS.

What should the optimal intrauterine pressure be during outpatient diagnostic hysteroscopy? A randomized comparative study.

AIM: The aim of this study was to evaluate and compare lower and higher uterine filling pressures during outpatient diagnostic hysteroscopy. METHODS: One hundred and seventy-five women eligible for outpatient diagnostic hysteroscopy were included in this randomized double blind comparative study. The subjects were randomized into two groups. Group 1 (n = 80) underwent surgery with lower intrauterine filling pressures (30, 40, and 50 mmHg) and group 2 (n = 81) underwent surgery with higher filling pressures (70, 80, and 100 mmHg). The primary outcome measure was adequate visibility during the procedure. The secondary outcome measure was pain perceived by the patient during and 30 min after the procedure. RESULTS: In total, 161 patients completed the trial. Group 2 had significantly higher adequate visibility than group 1 (71/80, 88.75% in group 1 and 79/81, 97.5% in group 2, P = 0.008). There was a trend toward increase in pain scores with higher pressures during the procedure. However, there were no significant differences between the two groups in terms of visual analog scale pain scores measured 30 min after the procedure. CONCLUSION: Lower uterine filling pressure was associated with lower pain scores with a higher trend towards inadequate visibility. It appears that higher filling pressure can be used for performing office hysteroscopy, but it is associated with higher pain scores.

Chemerin level in pregnancies complicated by preeclampsia and its relation with disease severity and neonatal outcomes.

The aims of this prospective study were to detect maternal serum chemerin level in patients with preeclampsia and investigate its association with disease severity and neonatal outcomes. Maternal serum chemerin levels were significantly elevated in severe preeclamptic women (394.72 ± 100.01 ng/ml) compared to mild preeclamptic women (322.11 ± 37.60 ng/ml) and healthy pregnant women (199.96 ± 28.05 ng/ml) (p = .001). Maternal serum chemerin levels were positively correlated with systolic and diastolic blood pressure, C-reactive protein levels, homeostasis model assessment of insulin resistance, proteinuria, AST, ALT, and duration of hospitalisation. Gestational week at delivery, birthweight, and APGAR scores at 1 and 5 min were negatively correlated with maternal serum chemerin level. A maternal serum chemerin level of >252.0 ng/ml indicated preeclampsia with 95.5% sensitivity and 95.7% specificity. There was a positive correlation between maternal serum chemerin level and severity of preeclampsia. Additionally, adverse neonatal outcomes were significantly associated with high maternal serum chemerin levels.

The role of ovarian reserve markers in prediction of clinical pregnancy.

To evaluate the role of ovarian reserve markers in the prediction of clinical pregnancy and embryo transfer accomplishment among poor responder IVF applicants. 304 female poor responder IVF applicants were included in this prospective cohort study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF outcomes were compared in pregnant and non-pregnant groups as well as in ET vs. non-ET groups. The number of retrieved oocytes was significantly correlated positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and <25%/>75%) were statistically significant. Mean serum levels for AMH were significantly lower in the non-ET group. Our findings seem to indicate that day 3 AMH values can predict ET accomplishment with a sensitivity of 96% and a specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF results among poor responder IVF applicants. Impact statement Various cut-off values have been determined for day 3 serum AMH values. These values help to determine the groups that are expected to give normal, high or low response to stimulation and decide the treatment options. In contrast to other groups of patients, poor responders cannot reach the embryo transfer stage for several reasons. These are; absence of a mature oocyte after oocyte pick-up, fertilisation failure without male factor or poor embryo quality. In the present study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in poor responder patients was determined with a sensitivity of 96%. Additionally, clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH values. It is important to clarify the embryo transfer success of poor responder patients prior to expected treatment success. Pre-treatment counselling for these patients would lessen the disappointment that may develop after treatment. The cost-effectiveness of treatments below these AMH values can be determined by further studies.

The impact of low molecular weight heparin on obstetric outcomes among unexplained recurrent miscarriages complicated with methylenetetrahydrofolate reductase gene polymorphism.

OBJECTIVES: The association between methylenetetrahydrofolate reductase gene polymorphisms and unexplained recurrent miscarriage is elusive. The recommendations for improving pregnancy outcomes in these patients keep changing based on the available evidence. The aim of this study is to analyze the impact of low molecular weight heparin on obstetric outcomes of recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphism. MATERIAL AND METHODS: We reviewed medical records of 121 patients with a history of recurrent miscarriage complicated by methylenetetrahydrofolate reductase gene polymorphisms, retrospectively. From among them, 68 patients were treated only with folic acid and iron. The remaining 53 patients were treated with folic acid, iron and prophylactic doses of low molecular weight heparin. The subsequent pregnancy outcomes of these patients were noted. RESULTS: The live birth rate was higher in patients with anticoagulant therapy than in patients without anticoagulant therapy (48.5% vs. 69.8%, respectively, p: 0.015) and the congenital anomaly rate was lower in anticoagulant therapy group (17.6% vs. 3.8%, respectively, p: 0.022). The other obstetric outcomes were found to be similar between the two groups. CONCLUSIONS: The current study demonstrated that low molecular weight heparin improved the live birth rates among unex-plained recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphisms. How-ever, the routine use of low molecular weight heparin did not improve the late pregnancy complications in these selected patients in the eastern region of our country. Further studies are needed to discriminate the effect of anticoagulation on the live birth rate of each of methylenetetrahydrofolate reductase gene polymorphism type.