Platelet Glycoprotein Receptor Ia-C807T and IIIa-PlA1/PlA2 Genetic Polymorphisms Are Associated With Enhanced Platelet Function in Women With Recurrent Miscarriages.

INTRODUCTION: Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages. METHODS: This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100. RESULTS:  In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds; relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean: 121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the median and OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. CONCLUSION: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promote the analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

Maternity blues: risk factors in Greek population and validity of the Greek version of Kennerley and Gath's blues questionnaire.

Aim: To validate the Greek version of Kennerley and Gath's Blues Questionnaire (BQ) and gather further knowledge on maternity blues (MB) associations with certain clinical and sociodemographic factors in Greek population.Material and methods: 116 postpartum women, who met the inclusion criteria, completed the Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the third day after delivery. Sociodemographic and clinical data were also collected.Results: Fifty women (43.1%) experienced severe MB on the third day postpartum. Lower number of previous births, fewer years of marriage, and husband's occupation were found to be associated with MB occurrence. Of them, years of marriage (odds 0.21, p = .001) and husband's occupation in private sector (odds 1.21, p = .04) were independent predictors of MB in logistic regression analysis. Cronbach's α for the total 28-item Greek version of BQ was 0.85. Cluster analysis in our data showed that the optimal number of clusters of BQ items was 4; these four clusters of items presented similarities with the Bartholomew and Horowitz's four-category model of attachment styles (avoidant - dismissing, preoccupied, secure, avoidant - fearful).Conclusions: The Greek version of Blues Questionnaire is a reliable tool for the detection and measurement of MB. Fewer years of marriage and the economic insecurity seem to have strong impact on the occurrence of MB. Further investigation is needed to evaluate whether the phenomenon of MB is associated with parental or mother-to-infant bonding disorders.

Altered Resistin Concentrations in Mid-trimester Amniotic Fluid of Fetuses With Trisomies 18 and 13: A Window onto the Pathophysiology of Trisomies 18 and 13.

BACKGROUND/AIM: The study aimed to examine whether resistin is present in second trimester amniotic fluid from pregnancies with trisomy 18 and 13 and evaluate its concentration in comparison with euploid pregnancies. PATIENTS AND METHODS: The study included 37 women who underwent amniocentesis. Eleven fetuses had trisomy 18, 3 had trisomy 13, while 23 had a normal karyotype. RESULTS: Resistin was detected in all cases. The mean level of resistin in trisomy 18 was statistically significantly lower compared to euploid controls. Resistin levels in all abnormal cases were below its median concentration in euploid controls. ROC analysis showed very good prognostic value for both trisomies. CONCLUSION: Resistin is a constituent of mid-trimester amniotic fluid of pregnancies with trisomies 13 and 18, exhibiting lower levels than those in euploid fetuses. The reduced levels of resistin in amniotic fluid may be associated with early changes in metabolic pathways and immunoinflammatory responses.

Gestational Diabetes and T-cell (Th1/Th2/Th17/Treg) Immune Profile.

BACKGROUND/AIM: Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by insulin resistance and low-grade systemic inflammation with a pro-inflammatory immune system response. Our objective was to study the peripheral Th1, Th2, Th17 and Treg response in GDM compared to normal pregnancy. MATERIALS AND METHODS: Th1, Th2, Th17 and Treg subsets was determined by flow cytometry based on staining for specific intracellular cytokines, as well as C-reactive protein (CRP) and total IgE circulating levels. The health status of all offspring was also assessed 6 months post-delivery. RESULTS: A total of 49 Caucasian adult pregnant women were enrolled into a GDM (n=26) and Control (n=23) group. At the third trimester of pregnancy, the GDM group had a higher proportion of Th2, Th17 and Treg cells compared to control. Contrary to the control group, the GDM group exhibited no significant change in the Th1/Th2/Th17/Treg profile postpartum. Furthermore, higher circulating CRP and total IgE levels were noted in the GDM group compared to controls. At the 6-month post-delivery assessment, 30.8% of the offspring from the GDM group were found to have developed atopic dermatitis, food allergy or allergic proctocolitis compared to none from the control group. CONCLUSION: Compared to an uncomplicated pregnancy, GDM exhibits a significantly different peripheral T-cell profile at the third pregnancy trimester characterized by higher proportion of Th2, Th17 and Treg cells which persist six months post-delivery, while the increased high sensitivity CRP (hsCRP) levels stressed the low-grade inflammatory profile of this disease.

Association between Brain-Derived Neurotrophic Factor (BDNF) Levels in 2nd Trimester Amniotic Fluid and Fetal Development.

The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid were collected from women who had undergone amniocentesis early in the 2nd trimester. All pregnancies were followed up until delivery and fetal growth patterns and birth weights were recorded, following which pregnancies were divided into three groups based on fetal weight: (1) AGA (appropriate for gestational age), (2) SGA (small for gestational age), and (3) LGA (large for gestational age). We focused on these three groups representing a reflection of the intrauterine growth spectrum. Our results revealed the presence of notably higher BDNF levels in the amniotic fluid of impaired growth fetuses by comparison with those of normal growth. Both SGA and macrosomic fetuses are characterized by notably higher amniotic fluid levels of BDNF (mean values of 36,300 pg/ml and 35,700 pg/ml, respectively) compared to normal-growth fetuses (mean value of 32,700 pg/ml). Though apparently small, this difference is, nevertheless, statistically significant (p value < 0.05) in SGA fetuses in the extremes of the distribution, i.e., below the 3rd centile. In conclusion, there is clear evidence that severe impairment of fetal growth induces the increased production of fetal brain growth factor as an adaptive mechanism in reaction to a hostile intrauterine environment, thereby accelerating fetal brain development and maturation.

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause.

The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

Polymorphisms of Platelet Glycoprotein Receptors and Cell Adhesion Molecules in Fetuses with Fetal Growth Restriction and Their Mothers As Detected with Pyrosequencing.

BACKGROUND: Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR. MATERIALS AND METHODS: We compared the maternal and fetal genotypic frequencies of single nucleotide polymorphisms (SNPs) in four genes coding for platelet receptors and cell adhesion molecules [integrin alpha subunit 2 (ITGA2)C807T, integrin subunit beta 3(ITGB3) T1565C, platelet cell adhesion protein 1 (PECAM1) CTG-GTG and selectin P(SELP)A/C]. A total of 32 fetuses with fetal growth restriction and their mothers were matched with 18 normal controls. Using maternal venous blood and umbilical cord blood samples, nucleotide sequences were determined from pyrograms. Genotypic frequencies were calculated and analyzed using appropriate tests and logistic regression. RESULTS: There was no statistical difference in the proportion of heterozygotes or homozygotes for any of the genotypic frequencies between FGR and control groups in mothers or fetuses. CONCLUSION: Our study demonstrated no association of maternal or fetal ITGA2 C807T SNP, ITGB3 T1565C SNP, PECAM1 CTG - GTG and SELP A/C polymorphisms with FGR.

mTOR downstream effectors, 4EBP1 and eIF4E, are overexpressed and associated with HPV status in precancerous lesions and carcinomas of the uterine cervix.

The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens. Whole protein extracts were analyzed for the expression of 4EBP1 and eIF4E proteins using western blotting. In addition, distribution of 4EBP1 and eIF4E protein expression and 4EBP1 phosphorylation (P-4EBP1) were analyzed by immunohistochemistry in archival tissues and correlated with the degree of dysplasia. The presence of high-risk HPV (HR-HPV) types was assessed by polymerase chain reaction. Using western blot analysis, high expression levels of 4EBP1 and eIF4E were observed in all uterine cervical carcinomas, which significantly correlated with the degree of dysplasia. By immunohistochemistry, overexpression of 4EBP1 and eIF4E was detected in 20 of 21 (95%) and 17 of 21 (81%) samples, respectively, in patients with high-grade dysplasia and carcinomas, compared with 1 of 20 (5%) and 2 of 20 (10%) samples, respectively, in patients with low-grade lesions or normal histology. All 4EBP1-positive cases tested were also positive for P-4EBP1. Furthermore, overexpression of 4EBP1 and eIF4E significantly correlated with the presence of HR-HPV oncogenic types. The present study demonstrated that critical effectors of mTOR signaling, which control protein synthesis initiation, are overexpressed in cervical high-grade dysplasia and cancer, and their levels correlate with oncogenic HPV types. These findings may provide novel targets for investigational therapeutic approaches in patients with cancer of the uterine cervix.

Chlamydia trachomatis infection and Vγ9Vδ2 Τ cells in women with recurrent spontaneous abortions.

PROBLEM: Vγ9Vδ2 T cells (γ9δ2) are involved in antibacterial immune responses. The aim of this study was to look for associations between peripheral blood (PB) γ9δ2 T cells and cervix/vaginal Chlamydia trachomatis (Ct) infection in women with recurrent spontaneous abortions (RSA). METHOD OF STUDY: Peripheral blood samples were obtained from 201 RSA women within 10 days after they experienced a new miscarriage. γ9δ2 T cells and their percentage in total γδ T cells were compared between women who had been found and women who had not been found infected with Ct (last 6 months). Fertile women (82) served as control subjects. RESULTS: The difference of mean percentages of γ9δ2 T cells between the abortion and control groups, and the Chlamydia (+) and Chlamydia (-) groups was highly statistically significant (P<.00001). Significant difference was also found between the Chlamydia (+) and Chlamydia (-) group and the control group (ANOVA). CONCLUSION: The measurement of γ9δ2T cells may be useful to suspect possibly undiagnosed chlamydial infection in RSA women.

Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome.

BACKGROUND: Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated. METHODS: In this cross-sectional study, one hundred and thirty-eight consecutive young patients presenting with amenorrhea or oligomenorrhea referred to an adolescent endocrinology and gynecology university clinic were studied. Clinical examination and an abdominal ultrasound were performed. Testosterone, free-testosterone, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, sex hormone binding globulin (SHBG), Δ4-androstenedione (Δ4A), free androgen index (FAI), insulin, glucose, thyroid stimulating hormone (TSH), total thyroxine (T4) (TT4), free T4 (FT4), total triiodothyronine (T3) (TT3) and free T3 (FT3). Concentrations were measured in blood samples. RESULTS: Patients with primary and secondary amenorrhea presented more often with body mass index (BMI) <18.5 and BMI >25 kg/m2, respectively. BMI values correlated positively with insulin (r=0.742) and glucose (r=0.552) concentrations and negatively with glucose/insulin ratio values (r=-0.54); BMI values and insulin concentrations correlated positively with FAI values (r=0.629 and r=0.399, respectively). In all patients, BMI values correlated positively and negatively with free testosterone (r=0.249) and SHBG (r=-0.24) concentrations, respectively. In patients with secondary amenorrhea insulin concentrations correlated negatively with SHBG concentrations (r=-0.75). In patients with oligomenorrhea BMI values correlated positively with insulin (r=0.490) and TSH (r=0.325) concentrations, and negatively with SHBG (r=-0.33) concentrations. Seventy-two percent, 21% and 7% of patients presented with TSH concentrations <2.5 µIU/mL, between 2.5 µIU/mL, 4.5 µIU/mL and >4.5 µIU/mL (subclinical hypothyroidism), respectively. Following the definition of polycystic ovary syndrome (PCOS) according to either the National Institutes of Health (NIH) criteria or those proposed in the literature by Carmina and his team, patients presented mainly with oligomenorrhea or secondary amenorrhea. There was good agreement between patients with amenorrhea or oligomenorrhea fulfilling both of the PCOS definition criteria employed. CONCLUSIONS: Among adolescent patients presenting with amenorrhea or oligomenorrhea for the first time those with low and high BMI present more often with primary and secondary amenorrhea, respectively. Obesity is involved in the development of hyperandrogenemia and hyperinsulinemia, particularly in PCOS patients. In these patients, subclinical hypothyroidism may be concealed and it should be investigated. These patients should be treated for abnormally increased or decreased BMI and be investigated for autoimmune thyroiditis.

Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

INTRODUCTION: Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship. MATERIALS AND METHODS: This is a narrative review of the current literature, following a search on MEDLINE and the Cochrane Library, from their inception until January 2012. Articles investigating gynecologic cancer (endometrial, ovarian, and breast) incidence in diabetic patients were extracted. RESULTS: The strong evidence for a positive association between diabetes mellitus and the risk for cancer indicates that energy intake in excess to energy expenditure, or the sequelae thereof, is involved in gynecological carcinogenesis. This risk may be further heightened by glucose which can directly promote the production of tumor cells by functioning as a source of energy. Insulin resistance accompanied by secondary hyperinsulinemia is hypothezised to have a mitogenic effect. Steroid hormones are in addition potent regulators of the balance between cellular differentiation, proliferation, and apoptosis. Inflammatory pathways may also be implicated, as a correlation seems to exist between diabetes mellitus and breast or endometrial carcinoma pathogenesis, although an analogous correlation with ovarian carcinoma is still under investigation. Antidiabetic agents have been correlated with elevated cancer risk, while metformin seems to lower the risk. CONCLUSION: Diabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.

The impact of Anastrazole and Letrozole on the metabolic profile in an experimental animal model.

Anastrazole and Letrozole are used as endocrine therapy for breast cancer patients. Previous studies suggested a possible association with metabolic and liver adverse effects. Their results are conflicting. Fifty-five 4-week-old female Wistar rats were allocated in 4 groups 1) ovariectomy control (OC), 2) ovariectomy-Anastrazole (OA) 3) ovariectomy -Letrozole (OL), 4) control. Serum glucose, cholesterol, triglycerides, HDL-c and LDL-c were measured at baseline, 2 and 4 months. At the end, the animals' liver were dissected for pathology. At 4 months, total cholesterol differed among the OC and OL groups (p = 0.15) and the control and OL groups (p = 0.12). LDL-C differed between the control and OC groups (p = 0.015) as well as between the control and OA (p =0 .015) and OL groups (p = 0.002). OC group triglycerides, differed from those of the OL group (p =0 .002) and the control group (p = 0.007). The OA also significantly differed from the OL (p = 0.50). Liver pathology analysis revealed differences among groups with favored mild steatosis and ballooning. Anastrazole and Letrozole seem to negatively influence the lipid profile in our experimental model. This information should be taken in caution by medical oncologists when addressing patients with altered lipid metabolism.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

OBJECTIVE: To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. INTERVENTION(S): A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. OUTCOME: Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. RESULTS: The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. CONCLUSIONS: AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

Dehydroepiandrosterone administration before IVF in poor responders: a prospective cohort study.

The use of dehydroepiandrosterone (DHEA) may improve ovarian stimulation outcomes in women of advanced reproductive age and could reduce embryo aneuploidy. In this prospective study, 48 women diagnosed with poor ovarian response received DHEA supplementation for at least 12 weeks. These women were compared with a group of poor responders (n = 113) who did not receive supplementation. During the study period, patients taking day 2 FSH and oestradiol were measured monthly before and after treatment. Stimulation characteristics, stimulation outcome and clinical outcome (clinical pregnancy and live birth rates) were reported. Evaluation of anti-Müllerian hormone (AMH) was carried out before initiation of treatment and immediately before the subsequent stimulation. Supplementation with DHEA for at least 12 weeks resulted in a modest, but statistically significant, increase in AMH levels and decrease in baseline FSH (P < 0.001 and P = 0.007, respectively). Administration of DHEA had no effect on any of the stimulation parameters nor was there any difference in clinical pregnancy rates and live birth rates between the two groups. Supplementation with DHEA significantly affects women with poor prognosis undergoing ovarian stimulation for IVF. Patients should be counselled about the uncertain effectiveness, potential side-effects and cost of this treatment.

Oocyte and embryo vitrification in the IVF laboratory: a comprehensive review.

Vitrification is an excellent tool in the IVF laboratory, enabling options and offering flexibility in assisted reproduction. The technology of cryopreservation has been underway since the early 20th century. The advent of vitrification has advanced the expectations in routine clinical practice in the IVF laboratory presenting impressive results both in post-thaw survival, and in clinical pregnancy rates, as well as significantly enhancing clinical results on preimplantation genetic diagnosis (PGD). Contradicting opinions have been published recently on the limitations and potential that vitrification has in the laboratory, as well as on the optimal approach to employ vitrification in IVF. This review aims to present a comprehensive analysis of the practical aspects of vitrification including concerns and options regarding its use on oocytes and embryos while comparing it with the traditional "slow-freezing" cryopreservation technique.

Neonatal birth waist is positively predicted by second trimester maternal active ghrelin, a pro-appetite hormone, and negatively associated with third trimester maternal leptin, a pro-satiety hormone.

INTRODUCTION: In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth. METHODS: Forty-two normal and thirty eight overweight women (mean±SD; age: 26.9±2.5years; pre-pregnancy BMI 26±2.2kg/m(2)) were seen during each of the three trimesters, had blood sampling and a 75g oral glucose tolerance test. At birth, neonates underwent anthropometry and cord blood sampling for c-peptide, glucose, insulin. RESULTS: During all three trimesters maternal weight correlated positively with percent total neonatal body fat while during the second and third trimesters it correlated positively with birth weight. The second trimester maternal active ghrelin levels correlated positively with neonatal waist and were its best positive predictor. The third trimester maternal active ghrelin levels correlated positively with neonatal waist and negatively with percent total neonatal body fat, fetal cord blood insulin levels and were the best negative predictor of the latter. The third trimester maternal leptin levels correlated negatively with neonatal waist. CONCLUSIONS: During pregnancy circulating maternal active ghrelin, a pro-appetite hormone, is associated with neonatal visceral energy storage (as expressed by neonatal waist). By inhibiting glucose-driven maternal insulin secretion, ghrelin might ensure adequate fasting glucose and nutrient supplies to the fetus while limiting overall fetal adipose tissue deposition.

Experiencing sexuality in youth living in Greece: contraceptive practices, risk taking, and psychosocial status.

STUDY OBJECTIVE: To assess initiation of sexual activity and contraception methods used among Greek adolescents. To determine the association of adolescents' emotional and behavioral status with their sexual activity. DESIGN: A descriptive cross-sectional survey was conducted. SETTING, PARTICIPANTS: The population (N = 1074, age 14-16) consisted of a random sample, stratified according to locality and population density, of 20 public junior high and high schools located in the urban district of Athens, Greece. INTERVENTIONS: Anonymous self-reported questionnaires were used to assess sexual activity choices and contraception methods. The Youth Self-Report questionnaire was used to evaluate the psychosocial competencies and difficulties of Greek adolescents. MEASURES: Analyses included frequencies with chi-square tests and multivariate logistic regression analysis. MAIN OUTCOME: Factors that may influence sexual engagement of Greek adolescents were assessed. RESULTS: Of the adolescents who completed the questionnaire 21.8% reported having experienced sexual intercourse. The male/female ratio was 3/1 (P < .001) and the mean age of sexual debut was 14.5 ± 0.9 years. Condoms were the most preferred contraceptive method (79.9%), followed by withdrawal (38.9%). Emergency contraception was used by 9.6% of participants. Adolescents with separated, divorced or with a deceased parent, and non-Greek nationality have higher possibility of being sexually active. Adolescents who reported sexual intercourse had significantly higher score of thought problems (ß = 1.07, SE = 0.35, P = .002), attention difficulties (ß = 0.67, SE = 0.29, P = .022), delinquent behavior problems (ß = 2.37, SE = 0.34, P < .001), aggressive behavior (ß = 1.97, SE = 0.48, P < .001), and externalizing problems (ß = 4.18, SE = 0.78, P < .001). CONCLUSIONS: Engagement in sexual activities was significantly associated with psychosocial difficulties among adolescents living in Greece.

Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old.

This prospective study examines if pre-treatment with two different doses of an oral contraceptive pill (OCP) modifies significantly the hormonal profile and/or the IVF/ICSI outcome following COS with a GnRH antagonist protocol. Infertile patients were allocated to receive either OCP containing 0.03 mg of ethinylestradiol and 3 mg of drospirenone, or OCP containing 0.02 mg of ethinylestradiol and 3 mg of drospirenone prior to initiation of controlled ovarian stimulation (COS) with recombinant gonadotropins on a variable multi-dose antagonist protocol (Ganirelix), while the control group underwent COS without OCP pretreatment. Lower dose OCP was associated with recovery of FSH on day 3 instead of day 5, but the synchronization of the follicular cohort, the number of retrieved oocytes and the clinical pregnancy rate were similar to higher dose OCP.

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17ß-estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05 ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73 ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.