Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. METHODS: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. FINDINGS: We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 µmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 µmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 µmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). INTERPRETATION: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 µmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. FUNDING: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.

Efficacy comparison of oral rosuvastatin versus oral progesterone and bevacizumab on regression of surgically endometriotic implants in rats.

This study hypothesizes that oral rosuvastatin, oral dienogest and intraperitoneal bevacizumab might improve endometriosis in randomly selected female Wistar albino rats with surgically endometriotic implants. Thirty female Wistar albino rats with surgically endometriotic implants were randomized into three treatment groups: oral rosuvastatin (20 mg kg/day; oral rosuvastatin group 1; n = 10), oral progesterone (dienogest group 2; n = 10) and intraperitoneal bevacizumab (2.5 mg/kg of single intraperitoneal injection of bevacizumab; bevacizumab group 3; n = 10), for 10 days. Post-treatment variables were compared. The oral rosuvastatin group showed higher reduction for the glandular epithelium and uterine vessels of histopathological scores values than the oral progesterone group (both, p < 0.017, respectively). The median glandular epithelium and uterine vessels and histopathological scores values did not show a statistically significant difference between group 1 and group 3 (p > 0.017). Endometrial thickness values and uterine volume values were more significantly reduced in the oral rosuvastatin group than the oral progesterone group (both, p < 0.017, respectively). Moreover, endometrial thickness and uterine volume values were not different in groups wecompared with group 3 (p > 0.017). In conclusion, oral rosuvastatin and intraperitoneal injection of bevacizumab may cause more significant regression of surgically endometriotic implants in rats than oral progesterone medications.

Serum levels of neopterin in gestational diabetes mellitus: the relationship with Apgar scores.

PURPOSE: This study was designed to evaluate neopterin levels and low Apgar scores in pregnancies with gestational diabetes mellitus (GDM) vs. normal control pregnancies. METHODS: We carried out a cross-sectional study by enrolling 81 pregnant women with GDM and 38 pregnant women without GDM. RESULTS: Maternal and cord blood neopterin levels were higher in women with GDM. There was a significant positive association between fasting blood glucose levels and maternal serum neopterin levels. The results of 50-g oral glucose challenge tests revealed a correlation between maternal and cord neopterin levels. Pregnancies complicated by GDM exhibited lower fetal Apgar scores than those of control subjects. The levels of cord blood neopterin were inversely correlated with an fetal Apgar score of 1 min in patients with GDM. CONCLUSIONS: Patients with GDM had higher maternal and cord blood neopterin levels, and the cord blood neopterin levels are inversely associated with lower Apgar scores in women with GDM. The neopterin levels might be potential predictors of low fetal Apgar scores in women with GDM.

Cornea in PCOS patients as a possible target of IGF-1 action and insulin resistance.

OBJECTIVES: Previous studies suggest that serum IGF-1 is higher in women with polycystic ovary syndrome (PCOS). The ophthalmologic effects of IGF-1 excess have not yet been investigated in women with PCOS. The aim of the current study is to compare the corneal thickness of patients with PCOS and those of healthy subjects. METHODS: Forty three patients with PCOS and 30 age-matched and gender-matched healthy individuals were enrolled in this cross-sectional study. Central corneal thickness (CCT) was measured in patients with PCOS and in healthy individuals with an ultrasound pachymeter. IGF-1 values were also determined in the study group. RESULTS: Women with PCOS had significantly higher levels of IGF-1 and homeostasis model assessment (HOMA-IR) levels than the control group. Right and left CCT measurements were higher in the PCOS group than in the control group. A positive correlation between IGF-1 and right and left CCT was identified in both groups. In multiple linear stepwise regression analyses, IGF-1 independently and positively associated with HOMA-IR in women with PCOS. A correlation between total testosterone and CCT was identified in the whole group. In multiple stepwise regression analyses, total testosterone independently and positively associated with left central corneal thickness in the whole group. CONCLUSIONS: These findings indicate that PCOS has target organ effects on the eye. Consequently, it can change central corneal thickness. Higher IGF-1 levels seem to be the main causes of increased corneal thickness. Insulin resistance in PCOS is one of the underlying causes and promotes increase in IGF-1. We suggest a careful and detailed corneal evaluation in PCOS patients to prevent the potential risk of increased CCT, in addition to the already-known complications.

Depressive symptomatology and quality of life assessment among women using the levonorgestrel-releasing intrauterine system: an observational study.

OBJECTIVE: The aim of our study was to examine the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) treatment on depressive symptoms, changes in bleeding patterns, and quality of life (QoL) among premenopausal women in our clinic. MATERIALS AND METHODS: We recruited 120 premenopausal women, aged 18-50 years, who had sought care in the previous year for menorrhagia. LNG-IUS was inserted into eligible patients after the relevant evaluations. Both questionnaires were administered at time of the initial screening before and 6 months after insertion of the LNG-IUS. All patients completed the 36-item Short-Form Health Survey (SF-36) for QoL and Beck's Depression Inventory for depressive symptoms. RESULTS: At the 6-month follow-up visit, the pictorial blood assessment chart score (PBAC) considerably decreased (p < 0.001). For SF-36 scores, physical functioning, physical role limitations, emotional role limitations, bodily pain, vitality, and mental health scores improved significantly after treatment (p < 0.001). Depression scores showed no significant difference from baseline to 6 months (p = 0.375). CONCLUSION: The LNG-IUS for the treatment of menorrhagia increases the QoL, and depression scores did not increase significantly in 6 months.

Follicle-Stimulating Hormone Receptor and Estrogen Receptor Gene Polymorphisms in Women With Discordant Follicle-Stimulating Hormone and Anti-Mullerian Hormone Levels.

Objective This study aimed to investigate follicle-stimulating hormone receptor (FSHR) polymorphisms (Thr307Ala and Asn680Ser), estrogen receptor 1 (ESR1) polymorphisms (PvuII and XbaI), and ESR2 polymorphisms (RsaI and AluI) in Turkish women with follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) discordance. Method Genotyping was performed in 60 patients aged 21-35 with FSH-AMH discordance and/or low ovarian reserve and 20 age-matched controls with normal FSH and AMH levels. The patients were investigated in four groups of 20 women according to their FSH and AMH levels. Groups 1, 2, 3, and 4 were as follows: normal FSH and low AMH levels, normal AMH and high FSH levels, high FSH and low AMH levels, and normal FSH and AMH levels. Genomic DNA was obtained from 3 cc peripheral blood, and polymorphisms were analyzed using TaqMan genotyping assays. Relations between groups of categorical variables were analyzed with a chi-square test. Differences between the groups were assessed using a student's t-test or Mann-Whitney U test. Results Women with discordant FSH and AMH levels (group 1 and group 2) were not statistically different from women with concordant FSH and AMH levels (group 3 and group 4) in terms of FSHR, ESR1, and ER2 single nucleotide polymorphisms (SNPs). Body mass index (BMI) was statistically significant between groups 1 and 2 as well as groups 2 and 3 (p = 0.004). Conclusions This study showed that FSHR, ESR1, and ESR2 SNPs have not had any effect on AMH-FSH discordance in reproductive age Turkish women.

Can first-trimester screening program detect women at high risk for gestational diabetes mellitus?

This study was designed to compare first-trimester maternal serum biochemical markers of aneuploidy and fetal nuchal translucency in pregnancies complicated by gestational diabetes mellitus and those of a control group. The study included 60 gestational diabetic and 60 control women who attended the first-trimester combined screening program for Down syndrome between 11 and 14 gestational weeks with complete follow-up data and delivered in our institution. Maternal serum free ß-human chorionic gonadotropin, pregnancy-associated plasma protein-A and fetal nuchal translucency were investigated. The combined risks, double test risks and age risks were calculated by PRISCA software version 4.0. Comparison of the results between the two groups yielded no significant differences in serum levels of free ß-human chorionic gonadotropin and fetal nuchal translucency. However, women who developed gestational diabetes mellitus had significantly lower pregnancy-associated plasma protein-A. And also, the combined risks and double test risks calculated by PRISCA software were statistically higher in gestational diabetic women than normal pregnant women. These results suggest that differences can be seen between diabetic and healthy pregnant women in first-trimester maternal serum biochemical markers of aneuploidy.

Relationship between mean platelet volume and low-grade systemic coagulation with vitamin D deficiency in primary ovarian insufficiency.

OBJECTIVE: Premature menopause in young women is associated with an increased incidence of cardiovascular disease. The present study was designed to determine vitamin D (vit D) and the coagulation parameters such as activated partial thromboplastin time (APTT), PT, D-dimer, white blood cell (WBC), and mean platelet volume (MPV) levels, in primary ovarian insufficiency (POI) patients and control women with a normal menstrual cycle. MATERIALS AND METHODS: A total of 43 patients with non-diabetic POI were studied in order to evaluate and compare with the control group comprising 33 women with a normal menstrual cycle. RESULTS: There was no significant difference between the groups for age and body mass index (BMI). D-dimer, WBC, MPV, PT, total cholesterol, and LDL cholesterol were higher in women with POI. APTT levels were also increased but missed the significance in POI group. Women with POI had significantly lower serum vit D levels compared with healthy control group. FSH level was positively correlated with D-dimer, WBC, MPV, and negatively correlated to vit D and serum D vit level was inversely correlated with MPV, APTT, D-dimer, FSH levels in individual women. CONCLUSIONS: The obtained results seem to indicate that POI patients had low-grade systemic coagulation and fibrinolytic activation as evidenced by elevated D-dimer, WBC, MPV, PT values potentially be used as indicators of risk factor for thrombosis and atherosclerosis in POI women. All of our patients with POI were deficient in vit D. These results also suggest that vit D deficiency plays important roles of POI women and associated with coagulation, independently from age and BMI.

Association Between Plasma Sclerostin Levels and Body Mass Index in Women With Polycystic Ovary Syndrome.

Background Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrine pathologies in females of reproductive age worldwide. This study investigated the relationship between serum sclerostin levels and body mass index (BMI) in women with PCOS. Methods Women aged 18-40 years who presented to our clinic between January 1, 2019, and January 1, 2020, and were diagnosed with PCOS were included in this study. The patients' clinical and laboratory data were recorded, and waist circumference, hip circumference, and BMI values were calculated. The patients with a BMI of >25 kg/m2 were evaluated as Group I, those with a BMI of <18.5 kg/m2 as Group II, and those with a BMI of 18.5-25 kg/m2 as Group III. Serum sclerostin levels were compared between the BMI groups. Results The study included 90 patients. The mean BMI values were 32.2±2.1, 17.0±0.9, and 22.9±2.1 kg/m2 for Groups I, II, and III, respectively. We detected a statistically significant difference in serum sclerostin levels between Group II and Group I (p<0.005). There was a significant, positive correlation between the sclerostin level and BMI (r=0.258, p=0.014), weight (r=0.237, p=0.044), waist measurement (r=0.225, p=0.045), and hip measurement (r=0.225, p=0.033). Conclusion This study revealed that abnormal body composition in PCOS could alter circulating sclerostin levels.

Serum Fetuin-A levels in women with polycystic ovary syndrome.

PURPOSE: The liver-derived Fetuin-A (α2-Heremans Schmid glycoprotein) is a circulating glycoprotein that may be related to insulin resistance and polycystic ovary syndrome (PCOS). We aimed to investigate the Fetuin-A levels in patients with PCOS. METHODS: A total of 88 women were included in the study. We measured the Fetuin-A levels in 44 women with PCOS and compared with 44 healthy women. RESULTS: The mean age in control group was 28.61±5.0 (18-38) and 25.5±4.1 (17-36) in PCOS group. While there was statistically significant difference in terms of age and testosterone levels, there was no difference in terms of smoking status and BMI between the groups. Accordingly, women with PCOS were older than controls [28.61±5.0 (18-38) and 25.5±4.1 (17-36), respectively, p=0.002]. The mean Fetuin-A level of PCOS group was 255.4±37.2 (203.1-388.9) ng/mL and the mean Fetuin-A level of control group was 253.0±43.2 (179.9-355.4) ng/mL. There was no difference between the groups with regard to Fetuin-A, before and after adjustment for age (p values 0.780 and 0.835, respectively). CONCLUSIONS: Serum Fetuin-A levels of women with PCOS did not change in comparison with the healthy controls.

Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients.

AIM: To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. METHODS: Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing ethinyl oestradiol-cyproterone acetate (EE/CA) and metformin (M; 850 mg metformin twice a day) were given for three cycles. Plasma sCD40L was measured before and after the treatment of 3 months. RESULTS: At baseline, the sCD40L levels of the patients with PCOS was significantly higher than those of control subjects (3.1 ± 2.0 vs. 2.05 ± 1.0, respectively; p=0.002). An average of 3 months of EE/CA-M therapy induced a significant decrease of sCD40L levels in the PCOS group (3.1 ± 2.0 vs. 2.5 ± 1.0; p=0.026). After having treated patients with PCOS, the sCD40L level was not completely normalised when compared to the healthy controls (2.5 ± 1.0 vs. 2.05 ± 1.0; p=0.039). CONCLUSIONS: PCOS is associated with elevated levels of sCD40L. Adding metformin therapy to EE/CA may decrease sCD40L levels in women PCOS. However, after the treatment for PCOS subjects, the sCD40L was not completely normalised when compared patients to healthy controls.

Effect of Closure of Anterior Abdominal Wall Layers on Early Postoperative Findings at Cesarean Section: A Prospective Cross-sectional Study.

OBJECTIVE: To investigate the effect of closure types of the anterior abdominal wall layers in cesarean section (CS) surgery on early postoperative findings. METHODS: The present study was designed as a prospective cross-sectional study and was conducted at a university hospital between October 2018 and February 2019. A total of 180 patients who underwent CS for various reasons were enrolled in the study. Each patient was randomly assigned to one of three groups: Both parietal peritoneum and rectus abdominis muscle left open (group 1), parietal peritoneum closure only (group 2), and closure of the parietal peritoneum and reapproximation of rectus muscle (group 3). All patients were compared in terms of postoperative pain scores (while lying down and during mobilization), analgesia requirement, and return of bowel motility. RESULTS: The postoperative pain scores were similar at the 2nd, 6th, 12th, and 18th hours while lying down. During mobilization, the postoperative pain scores at 6 and 12 hours were significantly higher in group 2 than in group 3. Diclofenac use was significantly higher in patients in group 1 than in those in group 2. Meperidine requirements were similar among the groups. There was no difference between the groups' first flatus and stool passage times. CONCLUSION: In the group with only parietal peritoneum closure, the pain scores at the 6th and 12th hours were higher. Rectus abdominis muscle reapproximations were found not to increase the pain score. The closure of the anterior abdominal wall had no effect on the return of bowel motility.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis.

BACKGROUND: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. METHODS: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 µmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. FINDINGS: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016). INTERPRETATION: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. FUNDING: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.

Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome.

OBJECTIVE: To determine the effects of different treatment regimens on the hormonal features, metabolic parameters, and hematologic variables in women with polycystic ovary syndrome (PCOS). METHODS: Forty-eight women with PCOS were randomized into four treatment protocols: ethinyl estradiol/cyproterone acetate (EE/CA; n =12), EE/CA-metformin (n = 12), metformin alone (n =12) and EE/CA-spironolactone (n =12). These treatment protocols were given for 3 months and pre- and post-treatment variables were compared. RESULTS: Activated partial thromboplastin time (APTT) and prothrombin time (PT) levels, D-dimer, HOMA-IR, insulin, WBC, MPV as well as androgen levels decreased in all treatment groups. EE/CA-metformin and metformin alone groups resulted in a higher proportional reduction of D-dimer levels than the other protocols, while no significant different proportional reduction was observed in all the four groups for MPV, WBC, APTT, PT values. EE/CA-metformin group showed higher proportional reduction fasting insulin concentrations, HOMA-IR and free testosterone levels than metformin alone and EE/CA-spironolactone groups. DHEAs levels significantly decreased in group EE/CA-metformin than EE/CA alone and EE/CA-spironolactone groups. In multiple stepwise regression analyses, reduction in proportional insulin levels was independently and positively associated with decrease of MPV, D-dimer, free testosterone levels. CONCLUSIONS: In all treatment groups, we observed reduced levels of coagulation parameters, improvement of hormonal, hematological and metabolical variables by most probably reducing insulin levels. Among the treatment groups, EE/CA-metformin may be a more effective therapeutic option than the other protocols and this may be due to the beneficial effect of EE/CA-metformin on insulin resistance.

Is increased maternal endothelin-1 concentration associated with neonatal asphyxia and preterm delivery in intrahepatic cholestasis of pregnancy?

OBJECTIVES: To evaluate plasma endothelin-1 (ET-1) and fetuin-A concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and to determine whether there is any association between these parameters and fetal asphyxia. METHODS: We carried out a prospective case-control study consisting of 32 women with ICP at third trimester of pregnancy and 32 pregnant women without ICP. Blood samples from maternal peripheral venous circulation were collected and ET-1 and fetuin-A levels were determined from the plasma samples. Pulse-wave Doppler and Apgar scores were also recorded. RESULTS: ET-1 concentrations were significantly higher in ICP patients. No difference was observed in fetuin-A levels between the two groups. Six newborns were declared as asphyctic (APGAR score at the 5 min <7). Maternal ET-1 levels did not correlate with the APGAR score at 5 min, total bile acid (TBA) and umbilical artery systolic/diastolic ratio with ICP patients. TBA levels were positively correlated with umbilical artery systolic/diastolic ratio negatively correlated with APGAR score at the 1' and 5'-Apgar score in all subjects. Plasma ET-1 concentration was higher in the preterm neonates of mothers with ICP compared with normal term neonates of mothers. CONCLUSIONS: Although these data did not show evidence that maternal ET-1 would be associated with fetal distress, we can speculate that maternal ET-1 may be playing a role in the underlying pathology regarding microvascular dysfunction especially in the preterm neonates of mothers with ICP. Elevated TBA levels may increase the risk of asphyxia whereas fetuin-a (as an anti-inflammation marker) does not seem to have effect in women with ICP.

Oral contraceptives alone and with spironolactone increase sCD40 ligand in PCOS patients.

BACKGROUND: The present study was designed to determine the effect of oral contraceptives (OCP) and OCP plus spironolactone (Sp) on plasma soluble CD40L levels in polycystic ovary syndrome (PCOS) patients. METHODS: Fifty-six women with PCOS were randomized into two treatment protocols: ethinylestradiol + cyproterone acetate (2 mg, EE/CA; n = 28), and EE/CA with spironolactone (Sp; n = 28). Plasma sCD40L levels were measured before and after a 3-month treatment. RESULTS: Before the initiation of treatment, the sCD40L levels were not significantly different between the groups [EE/CA (1.33 ng/mL) vs. EE/CA + Sp (1.23 ng/mL); P > 0.05]. In the post-treatment period, sCD40L concentrations were increased compared with pre-treatment values in the EE/CA and EE/CA + Sp groups (1.33 vs. 2.70 ng/mL, P = 0.011; and 1.23 vs. 2.41 ng/mL, P = 0.017; respectively). CONCLUSION: Increased plasma concentrations of sCD40L are associated with OCP and OCP + Sp treatment regimens in PCOS patients.

High mean platelet volume, low-grade systemic coagulation and fibrinolytic activation are associated with androgen and insulin levels in polycystic ovary syndrome.

OBJECTIVES: The present study was designed to determine (a) the coagulation parameters, WBC and MPV levels; (b) whether there was any association between androgen and mean platelet volume and low-grade systemic coagulation in PCOS patients. METHODS: A total of 48 patients with non-diabetic PCOS were studied in order to evaluate and compare with a non-PCOS group of 30 subjects. RESULTS: D-dimer, homeostatic model assessment (HOMA-IR), insulin, androgens, glucose, WBC and MPV concentrations were higher in women with PCOS. No difference was observed in fibrinogen, activated partial thromboplastin time and prothrombin time values between the two groups. Free testosterone was positively correlated with D-dimer, insulin, DHEAS, and MPV levels. In multiple stepwise regression analyses, free testosterone positively associated with D-dimer and DHEAS. MPV was positively correlated with insulin levels, HOMA-IR values, DHEAS and free testosterone levels in PCOS patients. In multiple stepwise regression analyses, MPV positively associated with insulin and DHEAS. CONCLUSION: PCOS patients had low-grade systemic coagulation and fibrinolytic activation as evidenced by elevated D-dimer, and increased WBC and MPV levels suggesting that hematological parameters could potentially be used as indicators of risk factor for atherosclerosis in PCOS women.

Urethral Coitus in a Case of Vaginal Agenesis - Is Only Vaginoplasty Enough to Treat the Urinary Problems?

Urethral coitus is an extremely rare condition. Megalourethra and urinary incontinence due to urethral coitus in vaginal agenesis are unusual manifestations because these patients usually present with primary amenorrhea before becoming sexually active and receive treatment. A 24-year-old woman came to our clinic because of primary amenorrhea, sexual dysfunction, dyspareunia, megalourethra and urinary incontinence five months after her marriage due to urethral coitus. Based on these clinical and radiological findings a diagnosis of Mayer-Rokitansky-Kuster-Hauser Syndrome was made and patient underwent modified McIndoe Vaginoplasty. The elasticity of female urethra permits repeated coitus, together with the physical damage can probably lead to incontinence. In this case, after eliminating the underlying cause of disease with vaginoplasty, no other treatment was required. The integrity of sphincteric function and structural support of urethra might be regained without subjecting the patient to aggressive reconstructive surgical procedures.

Is the Mean Platelet Volume a Predictive Marker of a Low Apgar Score and Insulin Resistance in Gestational Diabetes Mellitus? A Retrospective Case-Control Study.

INTRODUCTION: Gestational diabetes is defined as various degrees of glucose intolerance diagnosed or detected for the first time during pregnancy and is the most common metabolic complication of pregnancy. Early diagnosis and adequate treatment are important to prevent complications. Pre-eclampsia, polyhydramnios, fetalmacrosomia, and operative delivery are some of the complications seen in pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). AIM: The present study was designed to determine whether there was an association between Mean Platelet Volume (MPV) in predicting poor fetal outcome, insulin resistance, neonatal Apgar scores and gestational age for women with GDM. MATERIALS AND METHODS: In this retrospective study, we enrolled 101 pregnant women with GDM together with a group of 138 healthy controls. MPV, insulin and homeostatic model assessment (HOMA-IR) values were measured at 24-28 weeks of the pregnancy. An independent samples t-test was used to compare MPV values. Multivariate linear regression models were used to establish relations between MPV values, HOMA-IR, insulin levels and Apgar score. RESULTS: There was a significant positive correlation between MPV values, HOMA-IR and Insulin levels and a negative correlation with Apgar score at 1 min and 5 min in the GDM group (r=0.227, p=0.02; r=0.206, p=0.03; r=-0.485, p<0.001; and r=-0.399, p<0.001, respectively). In the multivariate logistic regression analysis, a high MPV value was most consistently associated with a low Apgar 1 min score (ß=-0.387, p=0.003) in the GDM group. An MPV of >8.0 fL had a sensitivity of 82% and a specificity of 75% for the prediction of GDM. CONCLUSION: We investigated the potential of MPV values in predicting low Apgar scores and insulin resistance in women with GDM.