Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Serum anti-Müllerian hormone levels in euthyroid adolescent girls with Hashimoto's thyroiditis: relationship to antioxidant status.

OBJECTIVE: Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of Hashimoto's thyroiditis (HT), which is the most common thyroid disorder in adolescents. HT requires lifelong thyroid surveillance, particularly in women of childbearing age to avoid adverse effects on reproductive function. The aims of this study were to investigate serum concentrations of anti-Müllerian hormone (AMH), a marker of ovarian reserve, in euthyroid adolescent girls with newly diagnosed HT and explore the relationships between AMH levels and biomarkers of antioxidant status. STUDY DESIGN: We recruited 57 non-obese (body mass index [BMI] Z-score<2) adolescent girls with newly diagnosed HT and 50 age- and BMI-matched healthy controls for this case-control study. All participants were euthyroid. Hormonal and metabolic parameters, serum levels of AMH, and antioxidant status [paraoxonase (PON) and arylesterase (ARE) activities] were assessed. RESULTS: Serum AMH levels were significantly higher and serum PON and ARE activities were significantly lower in adolescents with HT than in the controls (p<0.001 for all). No significant associations were detected between the AMH level and any of the clinical or biochemical parameters in the control group. Serum AMH levels were negatively correlated with PON (r=-0.435, p=0.001) and ARE (r=-0.422, p=0.001) activities in adolescents with HT. CONCLUSION: The AMH level was significantly higher while the PON and ARE activities were significantly lower in euthyroid adolescent girls with newly diagnosed HT.

Irisin as an early marker for predicting gestational diabetes mellitus: a prospective study.

OBJECTIVE: The objective of this study is to evaluate maternal serum irisin levels in the first and second trimesters of pregnancy in women diagnosed with and without gestational diabetes mellitus (GDM). METHODS: We performed a prospective, nested case-control study in 258 pregnant women who were enrolled at the time of the first prenatal visit (6-11th weeks of gestation) and followed until delivery. Among the entire population, we selected 20 women who subsequently developed GDM and 30 women with uneventful pregnancies. Blood samples were collected once from each participant at 6-11th weeks of gestation during the fetal viability scan and at 24-28th weeks of gestation during screening for GDM. RESULTS: In the first trimester, irisin levels were significantly lower in women who later developed GDM (median = 453 ng/mL, range: 257-811 ng/mL) than in controls (median = 721 ng/mL, range: 700-786 ng/mL). In the second trimester, the difference in irisin levels between the GDM group (median = 749 ng/mL; range: 456-910 ng/mL) and controls (median = 757 ng/mL; range: 703-898 ng/mL) was not statistically significant. CONCLUSIONS: Irisin may be a useful biomarker in early pregnancy to predict the development of GDM.

Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion.

The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n = 23), PHM (n = 24), and CHM (n = 23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.

Evaluation of circulating betatrophin levels in gestational diabetes mellitus.

Experimental data indicate that betatrophin plays a significant role in the regulation of lipid metabolism and glucose homeostasis. In recent years, considerable attention has focused on the relationship between betatrophin and diabetes mellitus in humans. This case-control study included 45 women diagnosed with gestational diabetes mellitus (GDM) and 45 pregnant healthy controls. The groups were matched for maternal and gestational age and body mass index. Serum betatrophin levels were significantly higher in women with GDM (median = 635.8 ng/L; range: 290-1841.6 ng/L) compared to control subjects (median = 320.1 ng/L; range: 94.6-936.8 ng/L; p = 0.001). No significant correlations were observed between serum betatrophin levels and clinical or biochemical parameters in the control group. However, in the GDM group, serum betatrophin levels were positively correlated with weight gain during pregnancy (r = 0.304, p = 0.042), systolic blood pressure (r = 0.394, p = 0.007), fasting insulin level (r = 0.348, p = 0.019), and homeostatic model assessment insulin resistance (HOMA-IR; r = 0.311, p = 0.038). Multivariate stepwise linear regression analysis revealed that fasting insulin levels (ß = 0.342, p = 0.022) and HOMA-IR (ß = 0.312, p = 0.037) were independently associated with serum betatrophin levels.

Do the first, second and third trimester maternal serum hepcidin concentrations clarify obstetric complications?

OBJECTIVE: To evaluate whether first, second, and third-trimester maternal serum hepcidin levels are different in pregnancies with and without adverse pregnancy outcomes (APO). METHODS: A 165 nullipar pregnant women were included in this prospective cohort study. Serum hepcidin, ferritin, IL-6, C-reactive protein (CRP) and Hb values were measured at 11-14, 24-28, and 30-34 weeks of gestation. The relation between these parameters and APO and neonatal outcomes were investigated. Preterm delivery, intrauterine growth restriction, pre-eclampsia, gestational hypertension and placental abruption were determined as adverse pregnancy outcomes. RESULTS: The risk of APO was three times higher in women with high IL-6 levels in the second trimester. High hepcidin levels in the second trimester were associated with a 1.6 times increased risk of APO. Newborns of women with high IL-6 levels in the third trimester had a 1.6-fold increased risk of neonatal complications. High ferritin levels in the third trimester were associated with minimally increased risk of neonatal complications. CONCLUSIONS: Mean serum hepcidin levels were similar in all pregnant women, however, elevated second trimester serum hepcidin and IL-6 levels were associated with a higher risk of APO and high third trimester hepcidin, ferritin and IL-6 levels were associated with higher risk of neonatal complications.

The impact of copper-containing and levonorgestrel-releasing intrauterine contraceptives on cervicovaginal cytology and microbiological flora: a prospective study.

OBJECTIVE: To compare vaginal microflora and cervical cytology before and after insertion of a copper-containing intrauterine device (Cu-IUD) or a levonorgestrel releasing-intrauterine system (LNG-IUS). METHODS: Between April 2009 and February 2011, all women requesting insertion of an intrauterine contraceptive for family planning or noncontraceptive indications were enrolled. One hundred and eight Cu-IUDs and 42 LNG-IUSs were placed. Cervical cytological and vaginal microbiological findings before insertion and after 12 months were recorded. RESULTS: With regard to cervical cytology, nonspecific inflammatory changes became more frequent (but not significantly so; p = 0.062) after one year of use of a Cu-IUD, whereas their prevalence remained unchanged among women fitted with a LNG-IUS. Colonisation by Candida spp. and mycoplasma infections were diagnosed significantly more often after one year of use of the Cu-IUD than at baseline. During the study period, women wearing a Cu-IUD complained significantly more frequently of vaginal discharge, pelvic pain, and increased menstrual flow. CONCLUSION: Use of a Cu-IUD - but not that of a LNG-IUS - was associated with an alteration of the vaginal flora and showed a trend towards a higher frequency of nonspecific inflammatory changes affecting cervical cytology.

Hepcidin, iron status, and inflammation variables among healthy pregnant women in the Turkish population.

PURPOSE: To investigate hepcidin levels in each trimester and their association with other haematological variables and inflammation markers during normal pregnancy among low-risk pregnant women in rural Turkey. METHOD: The series comprised 103 healthy Turkish primigravida women with a normal pregnancy. Blood samples were obtained at 11-14, 24-28 and 30-34 weeks of gestation. Haemoglobin, hematocrit, red cell indices, white blood cell count, platelet count, iron status indicators (plasma iron, transferrin, ferritin levels and iron binding capacity), serum hepcidin, interleukin-6 and C-reactive protein levels were analysed. The proportions were compared using Pearson's χ2 test or Friedman's test. RESULTS: The mean serum hepcidin concentrations at 11-14, 24-28 and 30-34 weeks of gestation were as follows: 7.8 ± 3.4 ng/mL, 8.6 ± 3.1 ng/mL and 7.3 ± 3.0 ng/mL, respectively. The mean serum ferritin concentrations with median values at each trimester were 14.2 (11.5), 9.5 (8.8) and 11.2 (9.3), respectively. The mean serum CRP values at each trimester were 5.1 (4.0), 5.5 (4.6) and 6.0 (5.5), respectively. The serum hepcidin levels were not related to iron status or the haemoglobin, IL-6 or C-reactive protein levels. CONCLUSIONS: There was no association between serum hepcidin and serum ferritin, IL-6 or CRP concentrations in each trimester among low-risk pregnant women.

Serum levels of visfatin and possible interaction with iron parameters in gestational diabetes mellitus.

BACKGROUND/AIMS: Visfatin is a novel adipokine with insulinomimetic properties that increases in diabetes. However, for gestational diabetes mellitus (GDM) there are conflicting reports. Recent studies have reported a positive association of serum ferritin concentrations with insulin resistance. Thus, we assessed serum levels of visfatin in pregnant women with varying degrees of glucose tolerance and investigated the possible interaction of visfatin with parameters of iron metabolism. METHODS: Visfatin levels were measured at 24-28 weeks of gestation in 88 women who were divided into three groups according to their response to a 50-gram glucose challenge test and a 100-gram oral glucose tolerance test: control group (n = 28), impaired glucose tolerance (IGT) group (n = 30) and GDM group (n = 30). RESULTS: Visfatin levels were significantly higher in the GDM and IGT group than in control (p < 0.001 for GDM vs. control, and p = 0.004 for IGT vs. control). Serum visfatin was significantly associated with serum ferritin, insulin, age, gravidity, and body mass index. In a linear regression model, the covariates explained only 17% of variability of serum visfatin concentration. Body mass index (p < 0.001) contributed independently to visfatin variance. CONCLUSION: Serum visfatin concentration is significantly higher in GDM and is correlated with ferritin levels.

Serum hepcidin is associated with parameters of glucose metabolism in women with gestational diabetes mellitus.

OBJECTIVES: Hepcidin is considered a major regulator of iron metabolism. Despite previous studies showing elevated ferritin and hepcidin levels in type 2 diabetes mellitus (DM), no study has investigated hepcidin levels in pregnant women with gestational DM (GDM). METHODS: A case-control study was conducted in 30 cases of GDM, 47 pregnant women with impaired glucose tolerance (IGT) and 72 pregnant women with normal glucose tolerance (control) between April 2009 and July 2011. Serum hepcidin and other iron metabolism parameters were analyzed in all groups. RESULTS: Serum ferritin and serum iron were significantly elevated in the GDM group compared to controls (p = 0.014, p = 0.018, respectively) and to the IGT group (p = 0.021, p = 0.008, respectively). Hepcidin levels were elevated significantly in the diabetic patients compared to the IGT group (p = 0.011) and controls (p = 0.002). We found no correlation between hepcidin and other iron metabolism parameters (Hb, serum iron and ferritin), whereas positive correlations were found between hepcidin and parameters of glucose metabolism (fasting blood glucose, fasting insulin level and glucose value response to glucose challenge test). CONCLUSIONS: Serum hepcidin concentrations were increased in pregnant women with IGT and GDM and this was not related to inflammation parameters.

Awareness and use of folic acid among reproductive age and pregnant women.

OBJECTIVE: Folic acid supplementation during the pre-conception period and first trimester of pregnancy reduces the incidence of neural tube defects (NTDs). In this study, our aim is to investigate knowledge and use of folic acid among women attending our clinic. MATERIAL AND METHODS: Between January 2012 and June 2012, 817 participants, consisting of 345 pregnant and 472 non-pregnant women, were enrolled in this survey. A questionnaire including socio-demographic information, knowledge and use of folic acid was applied. RESULTS: 48.2% of participants were aware of folic acid for the prevention of congenital anomalies. Knowledge and use of folic acid increase with socio-economic status and educational level. Participants who were already knowledgeable about folic acid cited health care professionals as common sources of information. Although 88.2% of the pregnancies were planned among the currently pregnant women, only 14.2% of them stated that they had used folic acid in the pre-conception period. The use of folic acid during the first trimester among pregnant women was 48.6%. Furthermore, 18.4% of participants had not used folic acid and 29.3% of them had not remembered whether they had or not. Even though 94.4% of health care professionals had heard about folic acid, 28.3% reported that they had used folic acid before pregnancy. CONCLUSION: It is thought that there is a relatively high incidence of NTD in Turkey, which is due to inadequate information about NTDs and the use of folic acid. Primarily health care professionals such as midwives, nurses and family physicians should aim to inform all reproductive age women about folic acid for the prevention of NTDs, who should be encouraged to take the supplement when planning pregnancy.

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy.

OBJECTIVE: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. METHODS: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. RESULTS: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free ß-human chorionic gonadotropin (ß-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. CONCLUSION: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.

Does vaginal irrigation with saline solution in women with infectious vaginitis contribute to the clinical and microbiological results of antibiotic therapy?

AIM: To compare the clinical and microbiological results between patients with infectious vaginitis receiving vaginal irrigation with saline or no irrigation before standard antibiotic therapy. METHODS: Women with vaginitis (n = 109) were randomized to receive vaginal irrigation with saline or no irrigation before standard antibiotic therapy. The vaginal symptoms perceived by subjects and clinical findings were assessed with a standardized scale during four follow-up visits, and Gram stain Nugent scores and vaginal fluid cultures were analyzed at each visit. RESULTS: Vaginal discharge (z = 7.159; p < 0.001), pruritus (z = 5.169; p < 0.001), itching (z = 2.969; p < 0.003) and odor scores (z = 2.303; p < 0.021) were significantly reduced in the study group compared to the control group between the first visit and 3-5 days after irrigation, before the start of antibiotic therapy. The second and third visits (15 and 30-45 days after antibiotic therapy) showed that the patients' symptoms and amounts of visible vaginal discharge did not differ between the two groups. Moreover, the microbiological cures of patients in each group did not differ at these visits (z = 0.447; p = 0.655). CONCLUSION: Vaginal irrigation with saline significantly reduces self-reported symptoms in the short term but has no effect on long-term clinical and laboratory results in women with infectious vaginitis.

Evaluation of risk factors and effect of physical activity in caesarean section in nulliparous women.

OBJECTIVE: The aim of this study was to evaluate risk factors for caesarean section (CS) in nulliparous women and to determine the effect of physical activity on ease of labour. METHODS: A prospective observational study, including 282 nulliparous women at 37-41 gestational weeks was conducted. Maternal demographic characteristics, obstetric history and Modified Grimby scale for evaluation of physical activity were noted. Patients were classified into spontaneous labour and induction group. Multiple logistic regression model was used to assess independent risk factors for type of delivery. RESULTS: Caesarean rate was increasing with higher educational status (p < 0.001). Maternal height, maternal and paternal age were higher, whereas dilatation on admission was lower in CS group (p < 0.05). Maternal age, weight gain and CS rate were higher in induction group (p < 0.05). Fetal distress as a cause of CS was detected higher in induction group (p < 0.05). Physical activity has no significant effect on mode of delivery (p > 0.05). Maternal height (p = 0.011), and cervical dilatation on admission (p = 0.004) were identified as predictor factors for CS. CONCLUSION: Cervical dilatation is the most important negative predictive factor for CS, whereas, moderate physical activity has no effect on mode of delivery. Fetal distress was the most frequent cause of CS in induction group.

Evaluation of risk factors in cesarean delivery among multiparous women with a history of vaginal delivery.

OBJECTIVE: To predict the risk of cesarean delivery (CS) for multiparous women who have undergone previous vaginal delivery. MATERIAL AND METHODS: A prospective observational study was performed, among multiparous pregnancies that were between 38 and 41 gestational weeks and had a singleton, vertex presentation fetus. Women's physical activity score, obstetric history, intrapartum and postpartum events were assessed. Multivariable logistic regression was used to explore risk factors associated with CS. RESULTS: Of the 245 total 83.7% had spontaneous labor and 16.3% were induced. Seventy-five percent of the induced women required CS, whereas only 19.5% of those with spontaneous labor required CS (p<0.001). The logistic regression analysis model included maternal weight gain, physical activity score, cervical dilatation, and fetal weight as the predictors of CS. We detected 7 (10%) maternal complications in women who underwent intrapartum CS. CONCLUSION: Labor induction is significantly associated with increased risk of cesarean delivery among previously vaginally delivered women and maternal weight gain, physical activity score, cervical dilatation, and fetal weight are most accurate parameters in the prediction of the risk of CS delivery. Intrapartum CS has an increased risk of maternal morbidity.

First trimester maternal serum PAPP-A and free ß-HCG levels in hyperemesis gravidarum.

OBJECTIVE: To evaluate whether hyperemesis gravidarum (HG) affects first-trimester maternal serum PAPP-A and free ß-hCG levels. METHOD: An observational study was conducted in 115 cases of HG and 110 control pregnancies who attended the first-trimester prenatal screening program between January 2006 and July 2010. RESULTS: Maternal serum TSH levels were lower and free T4, and transaminases (ALT, AST) levels were higher in pregnancies complicated with HG compared with controls (p < 0.05 for all). In HG cases, median values of maternal serum PAPP-A were significantly higher with respect to normal pregnancies (1.2 vs 1.0 MoM; p = 0.009). Similarly, median values of free ß-hCG were 1.3 MoM in HG pregnancies and 1.0 MoM in controls (p = 0.006). Multivariate analysis revealed that PAPP-A and hCG were independently associated with HG after controlling for TSH, free T4, AST, and ALT. CONCLUSION: HG is associated with elevated levels of PAPP-A and free ß-hCG, and such changes are independent of serum indicators of thyroid and liver function.