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We aimed to determine the second-trimester amniotic fluid (AF) levels of soluble Fas (sFas) and Fas-ligand (FasL) and investigate their association with fetal growth. Therefore, sFas and FasL levels were measured by enzyme immunoassay in the AF of 21 small for gestational age (SGA), 13 large for gestational age (LGA), and 44 appropriate for gestational age (AGA) fetuses of pregnant women who underwent amniocentesis at between 15 and 22 weeks gestation. Our study results showed that sFas and FasL levels were detectable in AF. sFAS median (25th-75th centile) levels were 3.8 (2.8-4.6). ng/ml in SGA, 3.6 (3.1-4.5). ng/ml in AGA, and 4.0 (3.1-4.4). ng/ml in LGA. FasL median (25th-75th centile) levels were 26.0 (20.3-32.7). pg/ml in SGA, 22.7 (18.4-28.5). pg/ml in AGA, and 21.5 (15.8-30.9). pg/ml in LGA. The differences were not statistically significant. Nevertheless, statistically significant differentiation of FasL levels existed when SGA fetuses in the extremes of distribution (≤5th, ≤2.5th centile) were considered. This is the first study presenting sFas and FasL concentrations in early second-trimester amniotic fluid in AGA, SGA, and LGA fetuses. We found indications that severe and very severe SGA fetuses (≤5th and ≤2.5th centile) have high levels of FasL in the amniotic fluid. This finding probably reflects the increased rate of apoptosis that is assumed to exist in cases of extreme growth restriction. © 2013 Elsevier Ireland Ltd.

The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA's role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52-100%), specificity (0-100%), and PPV (18-100%) and NPV (0-100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75-100%), good specificity (57-100%), and high PPV (79-100%) and NPV (68-100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting. © 2013 Paraskevi Vogiatzi et al.

There is an increasing need for clinician self-evaluation. The need becomes bigger when it comes to assess residents in operative procedures; office hysteroscopy in its current form is one of the best examples to teach and to assess them. We propose a simple protocol for the evaluation of residents in office hysteroscopy that can be used as a platform for future improvement. This will improve their learning experience and ensure that they do not miss any steps of the procedure. As each task is outlined on the evaluation checklist, it is easier to objectively demonstrate the strengths and deficiencies of each one with respect to the given procedure. This can be the basis for application of extra attention and highlights the areas in which each individual needs to improve. The advantage of recording parameters, such as duration of the procedure and pain scores, is that they can serve as tools that demonstrate acquisition of experience and of confidence. © 2013 Springer-Verlag Berlin Heidelberg.

Background: Hormone therapy (HT) is the treatment of choice for the alleviation of menopausal symptoms; concerns, however, about its concomitant long-term health risks have limited its use. DT56a is a unique enzymatic isolate of soybeans. The purpose of our study was to evaluate the efficacy and safety of DT56a, compared to HT, in symptomatic post-menopausal women. Subjects and methods: Eighty-nine post-menopausal women were studied prospectively. Women with climacteric symptoms were randomly assigned to receive eitherDT56a (no.=27) or oral low dose continuous combined HT (no.=26). Symptomatic women not wishing to receive any treatment served as controls (no.=36). Menopausal symptoms as assessed through the Kupperman index, serum lipids and lipoproteins, calcium, as well as bone mineral density (BMD), endometrial thickness, and mammography were assessed at baseline and at 12 months. Results: Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms (mean difference in Kupperman score, DT56a group: -3.98, HT group -5.601, no treatment group +1.76, p-value

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients. © 2013 Areti Augoulea et al.

Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure. © 2013 Charalampos Siristatidis et al.

Objective: The aim of this study was to examine whether resistin is present in second trimester amniotic fluid from trisomy 21 (also known as Down’s syndrome) pregnancies and whether its concentration differs compared with euploid pregnancies. Methods: The study cohort consisted of 58 women in the mid-trimester of pregnancy who underwent amniocentesis for prenatal diagnosis, 31 of whom carried a single fetus with diagnosed trisomy 21 (study group) and the rest with normal karyotype (control group, n = 27). Groups were matched for maternal and gestational age. Levels of resistin in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: Resistin was detected in all amniotic fluid samples. Its median concentration in the second trimester amniotic fluid of trisomy 21 pregnancies (2.1 ng/ml) was statistically significantly lower (p value

Through a non-randomized clinical trial, we examined the theoretical benefit of the coadministration of low molecular weight heparin (LMWH) and prednisolone on pregnancy outcomes in women with previously failed IVF/ICSI cycles. Fifteen women constituted the study group, and were compared with 19 women receiving LMWH alone and another 18 women with no drugs. Our finding that the combination of the two drugs produced positive differences in terms of embryo quality, pregnancy and live birth rates points to the necessity for adequately powered randomized trials. © 2013 The British Fertility Society.

Gestational diabetes, occurring during the hyperglycemic period of pregnancy in maternal life, is a pathologic state that increases the incidence of complications in both mother and fetus. Offspring thus exposed to an adverse fetal and early postnatal environment may manifest increased susceptibility to a number of chronic diseases later in life. Compelling evidence for the role of epigenetic transmission in these complications has come from comparison of siblings born before and after the development of maternal diabetes, exposure to this intrauterine diabetic environment being shown to cause alterations in fetal growth patterns which predispose these infants to developing overweight and obesity later in life. Diabetes of the offspring is also mainly the consequence of exposure to the diabetic intrauterine environment, in addition to genetic susceptibility. Since obesity and diabetes are known to increase the risk of cardiovascular disease, cardiovascular sequelae in the offspring of diabetic mothers are virtually inevitable. Research data also suggest that exposure to a diabetic intrauterine environment during pregnancy is associated with an increase in dyslipidemia, subclinical vascular inflammation, and endothelial dysfunction processes in the offspring, all of which are linked with development of cardiovascular disease later in life. The main underlying mechanisms involve persistent hyperglycemia hyperinsulinemia and leptin resistance. © 2012 Nikolaos Vrachnis et al.

Objective. We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results. The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8ng/mL). Conclusion. Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesis. Copyright © 2012 S. Iliodromiti et al.

Objective: The temporal bone may be the first involved site in cases of systemic disease, and may even present with acute, mastoiditis-like symptomatology. This study aimed to evaluate the incidence of such non-infectious ‘acute mastoiditis’ in children. Materials and methods: Retrospective chart review of 73 children admitted to a tertiary referral centre for acute mastoiditis. Results: In 71 cases (97.3 per cent), an infectious basis was identified. In the majority of cases (33 of 73; 45 per cent), the responsible bacteria was Streptococcus pneumoniae. However, histopathological studies revealed a non-infectious underlying disease (myelocytic leukaemia or Langerhans’ cell histiocytosis) in two atypical cases (2.7 per cent). Conclusion: ‘Acute mastoiditis’ of non-infectious aetiology is a rare but real threat for children, and a challenging diagnosis for otologists. A non-infectious basis should be suspected in every atypical, persistent or recurrent case of acute mastoiditis.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting 5-10% of reproductive-age women. Hyperandrogenemia, which characterizes the syndrome, stimulates the maturation of adipocytes and favors central obesity. The linking hub between obesity and other metabolic manifestations of the syndrome seems to be chronic low-grade inflammation. We discuss the most reliable current data regarding the role of inflammatory mediators in PCOS, with particular focus on the genetic mechanisms implicated. C-reactive protein levels are 96% higher in PCOS patients than in healthy controls. Patients with the -308A polymorphism of the tumor necrosis factor-a gene have elevated androgens in comparison with carriers of the -308G. Interleukin 18(IL-18) is elevated in lean patients, with a further rise in the presence of obesity and insulin resistance. Polymorphisms of the IL-1a, IL-1b and IL-6 genes have also been associated with PCOS. Plasminogen activator inhibitor-1 levels are positively associated with the syndrome, and carriers of the 4G allele of the 4G/5G polymorphism are at risk of developing PCOS. Other mediators discussed include adhesion molecules, osteoprotegerin, asymmetric dimethylarginine, homocysteine and advanced glycation end-products. The elucidation of the pathogenetic mechanisms implicated in PCOS and their connection with low-grade inflammation may in the future offer the opportunity for the formulation of novel therapeutic strategies and individualized therapy for these patients.

Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, adiponectin, leptin, Retinol-Binding Protein-4 (RBP-4), and resistin. These substances as well as other inflammatory mediators (CRP, IL-6, PAI-1, TNF-) seem to play an important role in glucose tolerance and insulin sensitivity dysregulation in women with pGDM. We summarize the data available on the role of these molecules. Copyright © 2012 Nikolaos Vrachnis et al.

Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Specifically, chronic amniotic fluid inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, viral infections also appear to be involved. Recently, molecular genetic techniques have helped us better understand the underlying pathophysiologic processes. This is especially important because epidemiological and experimental studies indicate that intrauterine infection and inflammation constitute a risk factor for adverse neurological outcome in preterm infants. Chronic subclinical chorioamnionitis associated with preterm birth can also modify lung development. Although no current clinical strategy is aimed at adapting the maternofetal inflammatory response, immunomodulators may serve as a future intervention in preterm embryos.

OBJECTIVE: To determine during mid-trimester amniocentesis if elevated concentrations of ADAM-8 (A Disintegrin And Metalloprotease 8) and/or cortisol can recognize women at risk for spontaneous preterm delivery. METHODS: The study involved 312 women who underwent mid-trimester amniocentesis. Thirteen patients, who progressed to preterm delivery, were matched with 21 controls for age, parity, gestational age at amniocentesis, and year of amniocentesis. ADAM-8 and cortisol levels were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: ADAM-8 mean amniotic fluid concentrations were significantly higher in women with preterit delivery than in women delivering at term (mean 1213.9 [SE 96.7] pg/mL [range, 780 to 1854 pg/mL] vs mean 937.2 [SE 50.3] pg/mL [range, 486 to 1508 pg/mL], P < .02). Amniotic fluid ADAM-8 concentrations higher than 1149 pg/mL had the highest specificity and odds ratio (OR) in the identification of the women with increased risk for preterm delivery (sensitivity 61.5%; specificity 81.7%; OR, 9.6 [95% confidence interval (CI), 1.8 to 50.3]). Women with preterit delivery had suggestively higher amniotic fluid concentrations of cortisol (meant 1.3 [SE 0.2] mu g/dL [range, 0.4 to 2.2 mu g/dL]) than women delivering at term (meant 1.0 [SE 0.09] mu g/dL [range, 0.6 to 1.7 mu g/dL], P < .07). Furthermore, cortisol levels were positively correlated with ADAM-8 levels (Spearman’s r = .418, P < .014). CONCLUSIONS: Elevated paid-trimester amniotic fluid ADAM-8 concentrations possibly are a risk factor,for preterm delivery, particularly if ADAM-8 levels are greater than 1149 pg/mL. Potential intrauterine inflammation is also associated with suggestively increased amniotic fluid cortisol levels.

Interferon-γ-inducible T cell-α chemoattractant (ITAC) is a chemokine, directing activated T lymphocytes toward sites of inflammation. ADAM-8 (A disintegrin and metalloprotease-8) is a glycoprotein expressed in cells promoting inflammation. Elastase, a protease targeting at the degradation of intra- or extracellular proteins, is inhibited by secretory leukocyte proteinase inhibitor (SLPI), which protects against microbial invasion. Adhesion molecules (soluble intercellular adhesion molecule - sICAM-1 and soluble vascular cell adhesion molecule - sVCAM-1) serve as markers of inflammation or tissue damage. We hypothesized that elevated midtrimester amniotic fluid concentrations of above substances, and decreased levels of SLPI could possibly be useful predictors of asymptomatic intra-amniotic inflammation and/or infection, eventually resulting in preterm labor and delivery. The study involved 312 women undergoing midtrimester amniocentesis. Thirteen cases, progressing to preterm delivery (37 weeks) for age, parity, and gestational age at amniocentesis. Amniotic fluid levels of the above substances were measured by enzyme-linked immunosorbent assay (ELISA). Only amniotic fluid ITAC and ADAM-8 levels were significantly higher (P = 0.005 and P < 0.02, respectively) in women delivering at 37 weeks. SLPI concentrations significantly increased in women going into labor without ruptured membranes irrespective of pre- or term delivery (P < 0.007, P < 0.001, respectively) and correlated with elastase (r = 0.508, P < 0.002). In conclusion, elevated midtrimester amniotic fluid levels of ITAC and ADAM-8 could predict occult infections/inflammations, possibly resulting in preterm birth. © 2006 New York Academy of Sciences.

Aims. Our aim is to investigate, in 13 cases (delivering preterm) and 21 matched (for age, parity, and gestational age) controls (delivering at term), whether midtrimester amniotic fluid concentrations of elastase, secretory leukocyte proteinase inhibitor (SLPI), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule predict asymptomatic intra-amniotic inflammation/infection and preterm labor. Results. Concentrations of all substances were not statistically different among mothers, delivering preterm or at term. SLPI concentrations significantly increased in women, going into labor without ruptured membranes, irrespective of pre- or term delivery (p

OBJECTIVE: To study the impact of intrauterine growth restriction (IUGR) on anti-angiogenesis, by determining and comparing circulatiug levels of the potent anti-angiogenic factor endostatin, in full-term IUGR (under the 10th customized centile) and appropriate for gestational age (AGA) fetuses, neonates, as well as their mothers, granted that IUGR implies hypoxia and endostatin is down-regulated by the latter. METHODS: In 20 IUGR cases (mainly due to hypertension or preeclampsia) and 20 AGA controls we determined circulating endostatin levels, by enzyme immunoassay in the serum of mothers (MS), umbilical cords (UC-mixed arteriovenous blood)-representing the fetal state, and asymptomatic neonates on day I (N1) and 4 (N4) of he-signifying transition and stabilization to extrauterine life, respectively. RESULTS: Endostatin levels were sigruicantly higher in AGA than IUGR UC, N1, and N4 (P < .0000, P = .0006, P = .024, respectively). Furthermore, UC endostatin levels positively correlated with the customized centiles of the infants (Spearman correlation coefficient 0.69, P = .00001). CONCLUSIONS: JUGR is characterized by lower circulating endostatin concentrations in the fetus and neonate, possibly because under lower oxygen concentrations an unbalanced state of angiogenesis stimulators versus inhibitors takes place. Copyright (c) 2005 by the Society for Gynecologic Investigation.