BioMed Research International: Obstetrics and Gynecology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Prediction of Outcome for Transabdominal Cerclage in Women with Cervical Insufficiency Wed, 25 Feb 2015 16:09:45 +0000 We investigated pregnancy outcome following transabdominal cerclage (TAC) in women with cervical insufficiency (CI) and explored parameters for predicting pregnancy outcomes following TAC. In this retrospective cohort study, we included 161 women with TAC. We considered demographic, obstetric, and gynecologic histories, pre- and postoperative cervical length (CL), and CL at 20–24 weeks as parameters for predicting outcomes following TAC. Univariate and multivariate analyses were used to identify risk factors for predicting delivery before 34 weeks after TAC. 182 pregnancies occurred after TAC, and 290 pregnancies prior to TAC were identified. The rate of delivery <34 weeks significantly decreased following TAC (5% versus 82%, ). Univariate analysis demonstrated that a short CL (<25 mm) at 20–24 weeks and adenomyosis were associated with delivery at <34 weeks’ gestation following TAC ( and , resp.). However, multivariate analysis demonstrated that only a short CL (<25 mm) at 20–24 weeks was a significant predictor (). TAC is an efficacious procedure that prolongs pregnancy in women with CI. A short CL at 20–24 weeks may predict the delivery at <34 weeks’ gestation following TAC. Ji Eun Song, Keun Young Lee, and Ga Hyun Son Copyright © 2015 Ji Eun Song et al. All rights reserved. Prevalence of Human Papillomavirus Variants and Genetic Diversity in the L1 Gene and Long Control Region of HPV16, HPV31, and HPV58 Found in North-East Brazil Sun, 22 Feb 2015 14:11:18 +0000 This study showed the prevalence of human papillomavirus (HPV) variants as well as nucleotide changes within L1 gene and LCR of the HPV16, HPV31, and HPV58 found in cervical lesions of women from North-East Brazil. Ana Pavla Almeida Diniz Gurgel, Bárbara Simas Chagas, Carolina Medeiros do Amaral, Kamylla Conceição Gomes Nascimento, Lígia Rosa Sales Leal, Jacinto da Costa Silva Neto, Maria Tereza Cartaxo Muniz, and Antonio Carlos de Freitas Copyright © 2015 Ana Pavla Almeida Diniz Gurgel et al. All rights reserved. Inhibition of Adhesion, Proliferation, and Invasion of Primary Endometriosis and Endometrial Stromal and Ovarian Carcinoma Cells by a Nonhyaluronan Adhesion Barrier Gel Sun, 15 Feb 2015 11:24:06 +0000 Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences. Stefan P. Renner, Pamela L. Strissel, Matthias W. Beckmann, Johannes Lermann, Stefanie Burghaus, Janina Hackl, Peter A. Fasching, and Reiner Strick Copyright © 2015 Stefan P. Renner et al. All rights reserved. Ethnogynaecological Assessment of Medicinal Plants in Pashtun’s Tribal Society Tue, 10 Feb 2015 07:32:46 +0000 The present study was designed to document detailed ethnogynaecological knowledge of selected remote regions of Pashtun’s tribe in northwest Pakistan. Semistructured questionnaires were designed to collect ethnogynaecological and ethnographic data. Total of 51 medicinal plants belonging to 36 families were documented that were used by the women of studied regions for the treatment of 9 types of gynaecological complaints. Majority of the plants (19) were found used against menses followed by 11 plants each for gonorrhea and pregnancy. Bannu region has high number of gynaecological plants (22) followed by Karak (15). Women of the regions mostly used whole plants (33%) and leaves (31%) for various ethnomedicinal preparation of gynae. Fic results showed that all ailments in different areas scored high consensus ranges between 0.6 and 1.00. Majority of the female respondents (44%) were aged between 61 and 70 years, of which most were illiterate. Women in the remote regions of Pakistan have tremendous traditional knowledge in utilizing medicinal plants for their reproductive health. Plants with high Fic values should be cross-checked for their in vitro and in vivo validation. Young girls should be educated on the importance of ethnogynaecological practices to conserve this valuable knowledge. Muhammad Adnan, Akash Tariq, Sakina Mussarat, Shaheen Begum, Naser M. AbdEIsalam, and Riaz Ullah Copyright © 2015 Muhammad Adnan et al. All rights reserved. Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study Wed, 04 Feb 2015 06:15:53 +0000 Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from “classic” GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26–3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12–3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis. Bruno Borghese, Jörg Tost, Magalie de Surville, Florence Busato, Frank Letourneur, Françoise Mondon, Daniel Vaiman, and Charles Chapron Copyright © 2015 Bruno Borghese et al. All rights reserved. American Ginseng Regulates Gene Expression to Protect against Premature Ovarian Failure in Rats Sun, 01 Feb 2015 13:27:42 +0000 Premature ovarian failure (POF) is defined as lost ovarian functions before the age of 40. Three possible molecular markers (PLA2G4A, miR-29a, and miR-144) have been identified in our previous study by integrated analysis of mRNA and miRNA expression profiles. The present study aimed to evaluate American ginseng root’s protective potential against POF by studying transcriptional and protein variations between American ginseng treatments and controls in rats. 4-Vinylcyclohexene diepoxide (VCD) was administered to rats for 14 days to induce POF. Additionally, American ginseng was administered to POF rats for one month, and PLA2G4A, miR-29a, and miR-144 expressions were measured in rat ovaries by qRT-PCR. PLA2G4A protein expression was examined by Western Blot, and PGE2, LH, FSH, and E2 serum levels were detected by ELISA. PLA2G4A mRNA and protein were downregulated in American ginseng-treated rats, miR-29a and miR-144 levels increased, and PGE2 serum levels decreased, while LH, FSH, and E2 increased compared to POF induction alone. Analysis of transcriptional and protein variations suggested that American ginseng protects the ovary against POF by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. High hormone levels (PGE2, FSH, and LH) were reduced, and E2 secretion approached normal levels, leading to improved POF symptoms and abnormal ovulation. Lei Zhu, Ji Li, Nannan Xing, Dongwei Han, Haixue Kuang, and Pengling Ge Copyright © 2015 Lei Zhu et al. All rights reserved. Three-Dimensional Modeling of the Pelvic Floor Support Systems of Subjects with and without Pelvic Organ Prolapse Sun, 01 Feb 2015 11:33:04 +0000 The purpose of this study was to develop three-dimensional finite element models of the whole pelvic support systems of subjects with and without pelvic organ prolapse (POP) that can be used to simulate anterior and posterior wall prolapses. Magnetic resonance imaging was performed in one healthy female volunteer (55 years old, para 2) and one patient (56 years old, para 1) with anterior vaginal wall prolapse. Contours of the pelvic structures were traced by a trained gynecologist. Smoothing of the models was conducted and attachments among structures were established. Finite element models of the pelvic support system with anatomic details were established for both the healthy subject and the POP patient. The models include the uterus, vagina with cavity, cardinal and uterosacral ligaments, levator ani muscle, rectum, bladder, perineal body, pelvis, obturator internus, and coccygeal muscle. Major improvements were provided in the modeling of the supporting ligaments and the vagina with high anatomic precision. These anatomically accurate models can be expected to allow study of the mechanism of POP in more realistic physiological conditions. The resulting knowledge may provide theoretical help for clinical prevention and treatment of POP. Shuang Ren, Bing Xie, Jianliu Wang, and Qiguo Rong Copyright © 2015 Shuang Ren et al. All rights reserved. Insufflation with Humidified and Heated Carbon Dioxide in Short-Term Laparoscopy: A Double-Blinded Randomized Controlled Trial Wed, 28 Jan 2015 15:36:35 +0000 Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment () or control () group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number  DRKS00003853 (German Clinical Trials Register (DRKS)). Anja Herrmann and Rudy Leon De Wilde Copyright © 2015 Anja Herrmann and Rudy Leon De Wilde. All rights reserved. Low Mutational Burden of Eight Genes Involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 Pathways in Female Genital Tract Primary Melanomas Wed, 28 Jan 2015 08:15:19 +0000 Mucosal melanomas exhibit discrete genetic features compared to cutaneous melanoma. Limited studies on gynecological melanomas revealed significant heterogeneity and low mutational burden. To gain further insight into their genetics and DNA repair efficiency, we systematically investigated the status of eight genes whose products are critically involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways, including BRAF, NRAS, HRAS, KRAS, c-KIT, PI3K, GNAQ, and GNA11, in a series of 16 primary gynecological melanomas, covering all anatomical locations, ranging from stages I to III. Analysis either by real-time PCR coupled with fluorescence melting curve analysis or by PCR followed by direct sequencing, along with studies for DNA mismatch repair status using immunohistochemistry, disclosed that 15 out of the 16 cases displayed wild-type genotypes, with a single case of vulvar primary melanoma, harboring the activating mutation . Investigations on whether this could reflect partly an efficient mismatch repair (MMR) mechanism were confirmed by normal expression of hMLH1 and hMSH2, suggesting that the lack of mutations could be explained by the operation of alternative pathogenetic mechanisms modulating downstream effectors of the signaling pathways. Our data suggest the presence of additional genetic components and provide the impetus for systematic approaches to reveal these yet unidentified genetic parameters. Kalliopi I. Pappa, George D. Vlachos, Maria Roubelakis, Dimitrios-Efthymios G. Vlachos, Theodora G. Kalafati, Dimitrios Loutradis, and Nicholas P. Anagnou Copyright © 2015 Kalliopi I. Pappa et al. All rights reserved. Validation of the Malay Version of the Inventory of Functional Status after Childbirth Questionnaire Thu, 15 Jan 2015 07:59:37 +0000 Objective. This study was designed to examine the psychometric properties of Malay version of the Inventory of Functional Status after Childbirth (IFSAC). Design. A cross-sectional study. Materials and Methods. A total of 108 postpartum mothers attending Obstetrics and Gynaecology Clinic, in a tertiary teaching hospital in Malaysia, were involved. Construct validity and internal consistency were performed after the translation, content validity, and face validity process. The data were analyzed using Analysis of Moment Structure version 18 and Statistical Packages for the Social Sciences version 20. Results. The final model consists of four constructs, namely, infant care, personal care, household activities, and social and community activities, with 18 items demonstrating acceptable factor loadings, domain to domain correlation, and best fit (Chi-squared/degree of freedom = 1.678; Tucker-Lewis index = 0.923; comparative fit index = 0.936; and root mean square error of approximation = 0.080). Composite reliability and average variance extracted of the domains ranged from 0.659 to 0.921 and from 0.499 to 0.628, respectively. Conclusion. The study suggested that the four-factor model with 18 items of the Malay version of IFSAC was acceptable to be used to measure functional status after childbirth because it is valid, reliable, and simple. Norhayati Mohd Noor, Aniza Abd. Aziz, Mohd Rosmizaki Mostapa, and Zainudin Awang Copyright © 2015 Norhayati Mohd Noor et al. All rights reserved. A Simple Sperm DNA Toroid Integrity Test and Risk of Miscarriage Thu, 15 Jan 2015 07:49:57 +0000 Current methods of analyzing sperm chromatin competency overlook the inner sperm compartment which is inaccessible to probes and reagents. By breaking the molecular protamine disulfide bridges, the DNA toroids are exposed to integrity analysis. The aim was to develop a simple nuclear toroid test and determine its association with fertilization, pregnancy, and miscarriage. The approach involved treating washed sperm remaining after ICSI procedures ( cases) with acidified Triton X-100 and dithiothreitol (DTT) before Diff-Quik staining. Percentages of sperm with normal chromatin indicated by light-colored nuclei were assessed. The toroid integrity test showed more sperm with normal chromatin in the pregnant group (73.6 ± 1.7%, mean ± SEM) when compared with the miscarriage (51.2 ± 6.6%) or nonpregnant groups (60.9 ± 4.8%). Furthermore, the toroid results were correlated with ICSI fertilization (, ) and pregnancy outcome (pregnant cases 73.6 ± 1.7% versus nonpregnant 58.0 ± 3.9%, ). ROC calculated cut-off was >70.0% for normal toroid integrity (sensitivity 0.98, specificity 0.33, and diagnostic accuracy 78.3%). An association between normal sperm toroid integrity and miscarriage was evident when the staining procedure included acidified detergent DTT pretreatment. Philip J. Chan, Eliza M. Orzylowska, Johannah U. Corselli, John D. Jacobson, and Albert K. Wei Copyright © 2015 Philip J. Chan et al. All rights reserved. Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood Wed, 14 Jan 2015 14:36:01 +0000 Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight <2,500 grams (g) was negatively correlated with (a) increased waist-to-hip ratio (WHR), according to regression coefficient (RC) equal to −0.323, 95% CI [−0.571, −0.075] ; (b) diastolic blood pressure (RC = −4.744, 95% CI [−9.017, −0.470] ); (c) low HDL-cholesterol (RC = −0.272, 95% CI [−0.516, −0.029] ); (d) frequency of intima-media thickness (IMT) of left carotid >75th percentile (RC = −0.242, 95% CI [−0.476, −0.008] ). Birthweight >3,500 g was associated with (a) BMI >25.0 kg/m2, (RC = 0.317, 95% CI [0.782, 0.557] ); (b) increased waist circumference (RC = 0.284, 95% CI [0.054, 0.513] ); (c) elevated WHR (RC = 0.280, 95% CI [0.054, 0.505] ); (d) minimum subcutaneous adipose tissue (SAT) (RC = 4.354, 95% CI [0.821, 7.888] ); (e) maximum SAT (RC = 7.095, 95% CI [0.608, 13.583] ); (f) right lobe of the liver side (RC = 6.896, 95% CI [1.946, 11.847] ); (g) frequency’s right lobe of the liver >75th percentile (RC = 0.361, 95% CI [0.169, 0.552] ). Weight gain in the first year of life was inversely correlated with (a) mean IMT of left carotid (RC = −0.046, 95% CI [−0.086, −0.006] ; (b) frequency IMT of left carotid >75th percentile (RC = −0.253, 95% CI [−0.487, −0.018] ); (c) mean IMT (RC = −0.038, 95% CI [0.073, −0.002] ); (d) the frequency of the mean IMT >75th percentile (RC = −0.241, 95% CI [−0.442, −0.041] ). Conclusions. Adults birthweight <2,500 g and >3,500 g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis. Maria Helena Valente, Filumena Maria da Silva Gomes, Isabela Judith Martins Benseñor, Alexandra Valéria Maria Brentani, Ana Maria de Ulhôa Escobar, and Sandra J. F. E. Grisi Copyright © 2015 Maria Helena Valente et al. All rights reserved. Neuroprotection in Preterm Infants Sun, 11 Jan 2015 13:26:01 +0000 Preterm infants born before the 30th week of pregnancy are especially at risk of perinatal brain damage which is usually a result of cerebral ischemia or an ascending intrauterine infection. Prevention of preterm birth and early intervention given signs of imminent intrauterine infection can reduce the incidence of perinatal cerebral injury. It has been shown that administering magnesium intravenously to women at imminent risk of a preterm birth leads to a significant reduction in the likelihood of the infant developing cerebral palsy and motor skill dysfunction. It has also been demonstrated that delayed clamping of the umbilical cord after birth reduces the rate of brain hemorrhage among preterm infants by up to 50%. In addition, mesenchymal stem cells seem to have significant neuroprotective potential in animal experiments, as they increase the rate of regeneration of the damaged cerebral area. Clinical tests of these types of therapeutic intervention measures appear to be imminent. In the last trimester of pregnancy, the serum concentrations of estradiol and progesterone increase significantly. Preterm infants are removed abruptly from this estradiol and progesterone rich environment. It has been demonstrated in animal experiments that estradiol and progesterone protect the immature brain from hypoxic-ischemic lesions. However, this neuroprotective strategy has unfortunately not yet been subject to sufficient clinical investigation. R. Berger and S. Söder Copyright © 2015 R. Berger and S. Söder. All rights reserved. Endometriosis: Novel Models, Diagnosis, and Treatment Tue, 30 Dec 2014 10:12:25 +0000 Renato Seracchioli, Giulia Montanari, Mohamed Mabrouk, and Joseph Nassif Copyright © 2014 Renato Seracchioli et al. All rights reserved. Prostaglandin E2 Labour Induction with Intravaginal (Minprostin) versus Intracervical (Prepidil) Administration at Term: Randomized Study of Maternal and Neonatal Outcome and Patient’s Perception Using the Osgood Semantic Differential Scales Mon, 29 Dec 2014 00:10:40 +0000 Aim. To compare the efficacy, safety, and patient’s perception of two prostaglandin E2 application methods for induction of labour. Method. Above 36th weeks of gestation, all women, who were admitted to hospital for induction of labour, were prospectively randomised to intravaginal 1 mg or intracervical 0.5 mg irrespective of cervical Bishop score. The main outcome variables were induction-to-delivery interval, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, rate of vaginal delivery, and patient’s perception using semantic differential questionnaire. Results. Thirty-nine patients were enrolled in this study. There was no statistical significant difference between the two groups in regard to perceptions of induction. The median induction delivery time using intravaginal versus intracervical administration was 29.9 versus 12.8 hours, respectively (). No statistically difference between the groups was detected in regard to parity, gestation age, cervical Bishop score, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, and mode of birth. Summary. Irrespective of the cervical Bishop Score, intracervical gel had a shorter induction delivery time without impingement on the women’s perception of induction. Joscha Reinhard, Roberta Rösler, Juping Yuan, Sven Schiermeier, Eva Herrmann, Michael H. Eichbaum, and Frank Louwen Copyright © 2014 Joscha Reinhard et al. All rights reserved. Ovarian Cancer Sun, 21 Dec 2014 08:03:30 +0000 Yong Sang Song, Hee Seung Kim, Daisuke Aoki, Danny N. Dhanasekaran, and Benjamin K. Tsang Copyright © 2014 Yong Sang Song et al. All rights reserved. Impact of Medical and Surgical Treatment of Endometriosis on the Cure of Endometriosis and Pain Mon, 15 Dec 2014 09:03:29 +0000 This endometriosis study evaluates three different treatment strategies (hormonal medication, surgical, or combined treatment) and discusses the influence of endometriosis on the cure of this disease and pain relief. Four hundred and fifty patients with genital endometriosis, aged 18–44 years, were randomly distributed to three treatment groups at the first laparoscopy. They were reevaluated at a second-look laparoscopy (D 426/10), one to two months after the three-month hormonal therapy for groups 1 and 3 and five to six months later for group 2 (surgical treatment alone). Outcome data focussed on the recurrence of symptoms and pain. The three treatment options independent of the initial endoscopic endometriosis classification (EEC) stage including deep infiltrating endometriosis (DIE) achieved an overall cure rate of 50% or higher. The highest cure rate of 60% was achieved by the combined treatment, 55% by the exclusively hormonal therapy, and 50% by the exclusively surgical treatment. An overall pregnancy rate between 55% and 65% was achieved with no significant difference in relation to the therapeutical option. Liselotte Mettler, R. Ruprai, and Ibrahim Alkatout Copyright © 2014 Liselotte Mettler et al. All rights reserved. Emodin Augments Cisplatin Cytotoxicity in Platinum-Resistant Ovarian Cancer Cells via ROS-Dependent MRP1 Downregulation Sun, 14 Dec 2014 13:15:10 +0000 The intracellular level of reactive oxygen species (ROS) is closely associated with chemosensitivity of cancer cells. Overexpression of ATP binding cassette transporter MRP1 is correlated with resistance to platinum drugs. In this study, we tested the hypothesis that emodin, a potent ROS generator, may increase sensitivity of cisplatin-(cDDP-) resistant ovarian carcinoma cells to cDDP cytotoxicity via ROS-mediated suppression of MRP1 expression. Using the isogenic pair of the human ovarian carcinoma cell line COC1 and its cDDP resistant variant COC1/DDP, we found that ROS level in the cDDP-sensitive ovarian cancer cells was significantly higher than that in the cDDP-resistant cells. Emodin enhanced ROS production in COC1/DDP cells and consequently sensitized them to cDDP-induced apoptosis. These effects were reversed by addition of the antioxidant N-acetyl-L-cysteine (NAC). Cotreatment with emodin and cDDP inhibited the tumor growth in vivo by increasing tumor cell apoptosis. The emodin-enhanced cDDP cytotoxicity was attributable to downregulation of multidrug resistance-related protein 1 (MRP1) expression. Together, these results suggest that emodin could act as an adjunct to enhance the anticancer effect of cDDP likely through ROS-related downregulation of MRP1 expression, and may be of therapeutic potential in cDDP-refractory ovarian carcinomas. Jun Ma, Jie Yang, Chao Wang, Nan Zhang, Ying Dong, Chengjie Wang, Yu Wang, and Xinjian Lin Copyright © 2014 Jun Ma et al. All rights reserved. Increased Serum Levels of Inflammatory Mediators and Low Frequency of Regulatory T Cells in the Peripheral Blood of Preeclamptic Mexican Women Sun, 07 Dec 2014 12:01:26 +0000 Regulatory T cells (; CD4+CD2Foxp3+) are critical in maintaining immune tolerance during pregnancy and uterine vascularization. In this study, we show that, in Mexican women with different preeclamptic severity levels, the number of and the subset of CD4+CD2Foxp3+ are decreased compared with those of normotensive pregnant women (NP). Moreover, a systemic inflammatory state is a pivotal feature in the pathogenesis of this disorder and could be related to hypertension and endothelial dysfunction. Likewise, we observed elevated levels of IL-6, TNF-α, and IL-8 in the serum of severe preeclamptic patients (SPE); no differences were found in the IL-1β and IL-10 levels compared with those of NP patients. An analysis of chemokines in the preeclamptic serum samples showed high levels of CXCL10, CCL2, and CXCL9. Our findings suggest that the preeclamptic state is linked with systemic inflammation and reduced numbers of . Mario Adan Moreno-Eutimio, José María Tovar-Rodríguez, Karina Vargas-Avila, Nayeli Goreti Nieto-Velázquez, María Guadalupe Frías-De-León, Mónica Sierra-Martinez, and Gustavo Acosta-Altamirano Copyright © 2014 Mario Adan Moreno-Eutimio et al. All rights reserved. Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis Sun, 07 Dec 2014 00:10:53 +0000 Objective. To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain. Laura Gaudet, Zachary M. Ferraro, Shi Wu Wen, and Mark Walker Copyright © 2014 Laura Gaudet et al. All rights reserved. Advanced Extrauterine Pregnancy at 33 Weeks with a Healthy Newborn Wed, 03 Dec 2014 13:32:01 +0000 Abdominal pregnancy is a very rare form of ectopic pregnancy, associated with high morbidity and mortality for both fetus and mother. It is, and often, seen in poor resource nations, where early diagnosis is often a major challenge due to poor prenatal care and lack of medical resources. An advanced abdominal pregnancy with a good fetal and maternal outcome is therefore a more extraordinary occurrence in the modern developed world. We present a case of an abdominal pregnancy at 33.4 weeks in an individual with no documented prenatal care, who arrived in a hospital in the Bronx, in June 25th 2014, with symptoms of generalized, severe lower abdominal pain. Upon examination it was found that due to category III fetal tracing an emergent cesarean section was performed. At the time of laparotomy the fetus was located in the pelvis covered by the uterine serosa, with distortion of the entire right adnexa and invasion to the right parametrium. The placenta invaded the pouch of Douglas and the lower part of the sigmoid colon. A massive hemorrhage followed, followed by a supracervical hysterectomy. A viable infant was delivered and mother discharged on postoperative day 4. Tajudeen Dabiri, Guillermo A. Marroquin, Boleslaw Bendek, Enyonam Agamasu, and Magdy Mikhail Copyright © 2014 Tajudeen Dabiri et al. All rights reserved. Development of a Provisional Model to Improve Transitional Care for Female Adolescents with a Rare Genital Malformation as an Example for Orphan Diseases Wed, 03 Dec 2014 11:34:56 +0000 Deficits of care exist during the transitional period, when young people with ongoing needs of support to achieve their physical, social, and psychological potential are entering adulthood. This study aims to develop a patient oriented, structured provisional model to improve transitional care for adolescents with Mayer-Rokitansky-Kuester-Hauser-Syndrome as an example for orphan diseases, where problems of access and continuity are even more complex. The study is funded by the German Federal Ministry of Education and Research (BMBF-Funding Code 01GY1125). The target patient group are young females with this disorder, treated at the Centre for Rare Genital Malformations in Women (ZSGF), University Hospital of Tuebingen. The study comprises five phases: an appraisal of literature, assessment of patients (), parents’, partners’, and health and social care providers’ () needs and experienced deficits in care and support in a qualitative approach, construction of a provisional model via scenario technique, followed by communicative validation (including interested public, ), preference finding, and identification of patient-oriented quality aims for follow-up. Quantitative data from questionnaires and chart review (as sociodemographic data, nonresponder analysis, and preference rating) are worked up for descriptive statistics. The results provide a platform for the development of future multidisciplinary transitional intervention programs in orphan diseases. Elisabeth Simoes, Andrea Kronenthaler, Christine Emrich, Monika A. Rieger, Kristin Katharina Rall, Norbert Schäffeler, Hanna Hiltner, Esther Ueding, and Sara Y. Brucker Copyright © 2014 Elisabeth Simoes et al. All rights reserved. A Rare Cause of Postpartum Low Back Pain: Pregnancy- and Lactation-Associated Osteoporosis Sun, 30 Nov 2014 00:10:42 +0000 Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis. It results in severe low back pain in the last trimester of pregnancy and in the postpartum period, decreases in height, and fragility fractures, particularly in the vertebra. The current case report presents a 32-year-old patient who presented with back and low back pain that began in the last trimester of the pregnancy and worsened at two months postpartum and who was diagnosed with pregnancy- and lactation-associated osteoporosis after exclusion of other causes; the findings are discussed in view of the current literature. PLO is a rare clinical condition causing significant disability. PLO must be kept in mind in the differential diagnosis in patients presenting with low back pain during or after pregnancy. The patients must be evaluated for the risk factors of PLO, and an appropriate therapy must be initiated. Rabia Terzi, Hasan Terzi, Tülay Özer, and Ahmet Kale Copyright © 2014 Rabia Terzi et al. All rights reserved. Breast Stimulation in Low-Risk Primigravidas at Term: Does It Aid in Spontaneous Onset of Labour and Vaginal Delivery? A Pilot Study Thu, 27 Nov 2014 06:44:39 +0000 Aims. The aim of the study was to elicit the safety and efficacy of breast stimulation as an intervention to prevent postdatism and as an aid in spontaneous onset of labour. Methods. Primigravidas with cephalic presentation, without any high-risk factor, were recruited between 36 to 38 weeks of gestation. 200 patients were recruited and randomized into two groups (n = 100). Breast stimulation was advised to one group but not to the other group. Bishop’s scoring was done at 38 weeks and repeated at 39 weeks of gestation. Maternal and fetal outcomes were compared in two groups. Result. Bishop’s score changed from 3.12 (±1.01) to 3.9 (±1.08) in control group and from 3.02 (±0.82) to 6.08 (±1.29) in breast stimulation group after one week ( value < 0.0001). The period of gestation at delivery was 39.5 (±2.3) weeks in control group and 39.2 (±2.8) weeks in intervention group ( value: 0.044). There were increased chances of vaginal delivery in intervention group (P value: 0.046). Duration of labor, hyperstimulation, presence of meconium stained liquor, postpartum hemorrhage, and neonatal outcomes were similar in both groups. Conclusion. Breast stimulation in low-risk primigravidas helps in cervical ripening and increases chances of vaginal delivery. Nilanchali Singh, Reva Tripathi, Yedla Manikya Mala, and Niharika Yedla Copyright © 2014 Nilanchali Singh et al. All rights reserved. Are There Differences in the Health Outcomes of Mothers in Europe and East-Asia? A Cross-Cultural Health Survey Thu, 27 Nov 2014 06:21:48 +0000 The aim of the current study was to investigate differences in quality of life outcomes and depression of mothers in East-Asia and Central Europe. 170 women in Japan and 226 women in Austria with children between 3 and 5 answered the same cross-culturally validated questionnaires. The Quality of Life Questionnaire from the WHO (WHOQOL-Bref), the Patient Health Questionnaire (PHQ-2), the Sense of Coherence Scale (SOC-13), a Social Support Scale (MSPSS), and questions on gender orientation were used. In all dimensions of QOL (physical, psychological, social, and environmental) Japanese women had lower QOL scores compared to Austrian mothers (). Seven percent of women in both countries experienced major depression. In both countries sense of coherence, experienced stress level, satisfaction with income, social support, and gender roles had an influence on QOL and depressive symptoms. Mothers in Japan consider life events less comprehensible, manageable, and meaningful and experience less support. Consequently, creating an environment where fathers could be more involved in child rearing and mothers have more opportunities to choose between life styles and working and social environments would improve QOL not only in Japanese mothers but also in other countries all over the world. Eva Mautner, Chie Ashida, Elfriede Greimel, Uwe Lang, Christina Kolman, Daniela Alton, and Wataru Inoue Copyright © 2014 Eva Mautner et al. All rights reserved. Perineal Ultrasound as a Complement to POP-Q in the Assessment of Cystoceles Thu, 27 Nov 2014 00:10:16 +0000 Purpose. In the present study we want to propose a classification system to quantify cystoceles by perineal ultrasound (PUS). Materials and Methods. 120 PUS data were analyzed measuring the distance between the lowest point of the bladder and the midpubic line (MPL) during rest and Valsalva. Results were classified into groups and compared to POP-Q using the -coefficient. Results for exact bladder position were checked for interrater reliability using ICC and Pearson’s coefficient and results for classification were checked using the κ-coefficient. Bladder positions at rest and Valsalva were correlated with the distance between these points. Results. Highly significant differences concerning the position at rest and the distance between rest and Valsalva were found between the groups. For the interrater agreement, the Pearson correlation coefficient was , the ICC (A-1) = 0.98, and . Comparing the classification results for POP-Q and PUS, the kappa-coefficient was . Conclusion. PUS using the MPL and the classification system is a highly reliable tool for the evaluation of cystoceles. PUS shows good correlation with POP-Q. Furthermore, PUS offers a doubtless identification of the descending organ. Further studies are needed to evaluate the clinical use of the classification system proposed here. Laila Najjari, Julia Hennemann, Pia Larscheid, Thomas Papathemelis, and Nicolai Maass Copyright © 2014 Laila Najjari et al. All rights reserved. Differentially Expressed MicroRNAs in Maternal Plasma for the Noninvasive Prenatal Diagnosis of Down Syndrome (Trisomy 21) Wed, 12 Nov 2014 08:46:15 +0000 Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS. Julian Kamhieh-Milz, Reham Fadl Hassan Moftah, Gürkan Bal, Matthias Futschik, Viktor Sterzer, Omid Khorramshahi, Martin Burow, Gundula Thiel, Annegret Stuke-Sontheimer, Rabih Chaoui, Sundrela Kamhieh-Milz, and Abdulgabar Salama Copyright © 2014 Julian Kamhieh-Milz et al. All rights reserved. Comparison of Low Urinary Tract Symptoms during Pregnancy between Primiparous and Multiparous Women Sun, 09 Nov 2014 13:25:11 +0000 Background and Purpose. Low urinary tract symptoms (LUTS) are a common problem during pregnancy. This study aimed to compare changes in the prevalence of LUTS during pregnancy between primiparous and multiparous women. Methods. A chart review of consecutive pregnant women who attended our antenatal clinic from March 2002 to January 2006 was performed. All of the women were asked to respond to a LUTS questionnaire in either of the three trimesters. Results. Of the 270 women included, 164 were nullipara and 106 were multipara. The most common LUTS during pregnancy were frequency (77%), followed by nocturia (75.6%), stress urinary incontinence (SUI) (51.1%), incomplete emptying (43.7%), dysuria (17.8%), and urgency incontinence (10.4%). There was a significantly higher prevalence of SUI () and urgency incontinence () in the multiparous compared to the nulliparous women. Increasing prevalence rates of frequency, nocturia, SUI, and incomplete emptying were reported with gestational age in both the nulliparous and multiparous women. Conclusions. Frequency and nocturia were the two most common LUTS during pregnancy. The prevalence rates of all LUTS increased with increasing gestational age except for frequency in the nulliparous women during the second trimester. In addition, multipara was a predictor of SUI during pregnancy. Kun-Ling Lin, Ching-Ju Shen, Ming-Ping Wu, Cheng-Yu Long, Chin-Hu Wu, and Chiu-Lin Wang Copyright © 2014 Kun-Ling Lin et al. All rights reserved. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study Wed, 05 Nov 2014 09:19:09 +0000 The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (: n.s.), underdiagnosis in 25.6% versus 41.4% (), and overdiagnosis in 11.6% versus 0% (). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events. Salvatore Gizzo, Roberto Berretta, Stefania Di Gangi, Maria Guido, Giuliano Carlo Zanni, Ilaria Franceschetti, Michela Quaranta, Mario Plebani, Giovanni Battista Nardelli, and Tito Silvio Patrelli Copyright © 2014 Salvatore Gizzo et al. All rights reserved. Early Second-Trimester Serum MicroRNAs as Potential Biomarker for Nondiabetic Macrosomia Mon, 27 Oct 2014 11:14:40 +0000 Background. Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. Methods. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. Results. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls ( for miR-194 and for miR-376a, resp.). Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (). Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity = 96.7% and specificity = 40.0%). Conclusions. Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia. Lingmin Hu, Jing Han, Fangxiu Zheng, Hongxia Ma, Jiaping Chen, Yue Jiang, and Hua Jiang Copyright © 2014 Lingmin Hu et al. All rights reserved. Efficacy of Intrauterine Device in the Treatment of Intrauterine Adhesions Mon, 01 Sep 2014 11:20:34 +0000 The primary purpose of this paper is to assess the efficacy of the use of the intrauterine device (IUD) as an adjunctive treatment modality, for intrauterine adhesions (IUAs). All eligible literatures were identified by electronic databases including PubMed, Scopus, and Web of Science. Additional relevant articles were identified from citations in these publications. There were 28 studies included for a systematic review. Of these, 5 studies were eligible for meta-analysis and 23 for qualitative assessment only. Twenty-eight studies related to the use of IUDs as ancillary treatment following adhesiolysis were identified. Of these studies, 25 studies at least one of the following methods were carried out as ancillary treatment: Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD. There was one study that used IUD therapy as a single ancillary treatment. In 2 studies, no adjunctive therapy was used after adhesiolysis. There was a wide range of reported menstrual and fertility outcomes which were associated with the use of IUD combined with other ancillary treatments. At present, the IUD is beneficial in patients with IUA, regardless of stage of adhesions. However, IUD needs to be combined with other ancillary treatments to obtain maximal outcomes, in particular in patients with moderate to severe IUA. Umme Salma, Min Xue, Ali Sheikh Md Sayed, and Dabao Xu Copyright © 2014 Umme Salma et al. All rights reserved. ABO and Rhesus Blood Groups and Risk of Endometriosis in a French Caucasian Population of 633 Patients Living in the Same Geographic Area Wed, 27 Aug 2014 00:00:00 +0000 Objectives. The identification of epidemiological factors increasing the risk of endometriosis could shorten the time to diagnosis. Specific blood groups may be more common in patients with endometriosis. Study Design. We designed a cross-sectional study of 633 Caucasian women living in the same geographic area. Study group included 311 patients with histologically proven endometriosis. Control group included 322 patients without endometriosis as checked during surgery. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. Results. We observed a higher proportion of Rh-negative women in the study group, as compared to healthy controls. Multivariate analysis showed that Rh-negative women are twice as likely to develop endometriosis (aOR = 1.90; 95% CI: 1.20–2.90). There was no significant difference in ABO group distribution between patients and controls. There was no difference when taking into account either the clinical forms (superficial endometriosis, endometrioma, and deep infiltration endometriosis) or the rAFS stages. Conclusion. Rh-negative women are twice as likely to develop endometriosis. Chromosome 1p, which contains the genes coding for the Rhesus, could also harbor endometriosis susceptibility genes. Bruno Borghese, Mélanie Chartier, Carlos Souza, Pietro Santulli, Marie-Christine Lafay-Pillet, Dominique de Ziegler, and Charles Chapron Copyright © 2014 Bruno Borghese et al. All rights reserved. LH Pretreatment as a Novel Strategy for Poor Responders Tue, 12 Aug 2014 09:25:20 +0000 Introduction. Poor response to ovarian stimulation is still a major problem in IVF. The study presents a new stimulation protocol evaluated in a suppopulation of very difficult young poor ovarian responders. Material and Methods. The study consists in two sections. The first includes data from a randomized controlled study involving forty-three young patients with a poor ovarian response in at least two previous cycles (intended as cycle cancellation or with ≤3 collected oocytes). Patients were randomized in two groups: group A (control) received FSH (400 IU/day), while group B received the new stimulation protocol consisting in a sequential association of 150 IU r-LH for 4 days followed by 400 IU r-FSH/after downregulation with daily GnRh agonist. The second includes data from the overall results in 65 patients treated with the new protocol compared to their previous performance with conventional cycles (historical control). Results. Both in the RCT and in the historical control study, LH pretreatment was able to decrease the cancellation rate, to improve the in vitro performance, and to significantly increase the live birth rates. Conclusions. LH pretreatment improved oocyte quantity and quality in young repeated poor responders selected in accordance with the Bologna criteria. Anna Pia Ferraretti, Luca Gianaroli, Tatiana Motrenko, Elisabetta Feliciani, Carla Tabanelli, and Maria Cristina Magli Copyright © 2014 Anna Pia Ferraretti et al. All rights reserved. A Disintegrin and Metalloproteinase 9 Is Involved in Ectodomain Shedding of Receptor-Binding Cancer Antigen Expressed on SiSo Cells Thu, 07 Aug 2014 13:00:53 +0000 In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. RCAS1 alters the tumor microenvironment by inducing peripheral lymphocyte apoptosis and angiogenesis, while reducing the vimentin-positive cell population. Although proteolytic processing, referred to as “ectodomain shedding,” is pivotal for induction of apoptosis by RCAS1, the proteases involved in RCAS1-dependent shedding remain unclear. Here we investigated proteases involved in RCAS1 shedding and the association between tumor protease expression and serum RCAS1 concentration in uterine cancer patients. A disintegrin and metalloproteinase (ADAM) 9 was shown to be involved in the ectodomain shedding of RCAS1. Given the significant correlation between tumor ADAM9 expression and serum RCAS1 concentration in both cervical and endometrial cancer as well as the role for ADAM9 in RCAS1 shedding, further exploration of the regulatory mechanisms by which ADAM9 converts membrane-anchored RCAS1 into its soluble form should aid the development of novel RCAS1-targeting therapeutic strategies to treat human malignancies. Kenzo Sonoda and Kiyoko Kato Copyright © 2014 Kenzo Sonoda and Kiyoko Kato. All rights reserved. Medical Treatments for Endometriosis-Associated Pelvic Pain Thu, 07 Aug 2014 00:00:00 +0000 The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors- ligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies. Gabriella Zito, Stefania Luppi, Elena Giolo, Monica Martinelli, Irene Venturin, Giovanni Di Lorenzo, and Giuseppe Ricci Copyright © 2014 Gabriella Zito et al. All rights reserved. Tumorigenic Factor CRIPTO-1 Is Immunolocalized in Extravillous Cytotrophoblast in Placenta Creta Wed, 06 Aug 2014 07:53:29 +0000 CRIPTO-(CR)1 is a protein associated with tumorigenesis and metastasis. Here we demonstrate that CR-1 expression in normal and creta placentas is associated with various degrees of uterine invasion. Cytokeratin (CK) and CR-1 protein expression was visualized by immunohistochemical staining of formalin-fixed, paraffin-embedded placental specimens (control placentas, ; accreta, ; increta, ; percreta, ). The pattern of extravillous trophoblast (EVT) cell morphology was distinctive in creta placentas: densely-compacted cell columns and large star-shaped cells with a typically migratory phenotype, not common among third trimester control placentas. Quantification revealed higher CR-1 immunoreactivities in accreta , increta , and percreta placentas than in controls. In contrast to controls, there was a significant positive relationship between CR-1 and CK reactivity in all creta placentas (accreta, ; increta, , and percreta, ). This study demonstrated CR-1 expression in the placental bed, its increased expression in creta placentas, and EVT cells as the main CR-1-producing cell type. Morphological examination revealed an immature and invasive trophoblast profile in creta placentas, suggesting impairment of the trophoblast differentiation pathway. These findings provide important new insights into the pathophysiology of abnormal creta placentation and its gestational consequences. Carla Letícia Bandeira, Alexandre Urban Borbely, Rossana Pulcineli Vieira Francisco, Regina Schultz, Marcelo Zugaib, and Estela Bevilacqua Copyright © 2014 Carla Letícia Bandeira et al. All rights reserved. Acceptability of Human Papillomavirus Vaccine: A Survey among Master of Business Administration Students in KwaZulu-Natal, South Africa Tue, 05 Aug 2014 00:00:00 +0000 Cervical cancer is a preventable public health problem. The two new human papillomavirus (HPV) vaccines are available but not accessible to everyone in South Africa, as they are very expensive. This study aimed to investigate educated peoples acceptability regarding HPV vaccination. This was a cross-sectional survey conducted among 146 master of business administration students by self-administered, anonymous questionnaire. The majority (74%) of the participants ever heard of cervical cancer, but only 26.2% heard about HPV. After reading the fact information regarding cervical cancer and HPV, the intention to vaccinate their daughters increased from 88% to 97.2% . The majority (75.4%) indicated that HPV vaccination should be given before their daughters are mature enough to understand about sex, and 80.3% reported that they will discuss matters related to sex with their daughters if their daughters want to know about the vaccine. Those who did not want to vaccinate their daughters highlighted that they want more information regarding safety of the vaccine which might change their decision towards HPV vaccination. A health education information method can increase the vaccination acceptance rate in South Africa. Muhammad Ehsanul Hoque and Guido Van Hal Copyright © 2014 Muhammad Ehsanul Hoque and Guido Van Hal. All rights reserved. Intrapartum Ultrasound Assessment of Fetal Spine Position Mon, 04 Aug 2014 00:00:00 +0000 We investigated the role of foetal spine position in the first and second labour stages to determine the probability of OPP detection at birth and the related obstetrical implications. We conducted an observational-longitudinal cohort study on uncomplicated cephalic single foetus pregnant women at term. We evaluated the accuracy of ultrasound in predicting occiput position at birth, influence of fetal spine in occiput position during labour, labour trend, analgesia request, type of delivery, and indication to CS. The accuracy of the foetal spinal position to predict the occiput position at birth was high at the first labour stage. At the second labour stage, CS (40.3%) and operative vaginal deliveries (23.9%) occurred more frequently in OPP than in occiput anterior position (7% and 15.2%, resp.), especially in cases of the posterior spine. In concordant posterior positions labour length was greater than other ones, and analgesia request rate was 64.1% versus 14.7% for all the others. The assessment of spinal position could be useful in obstetrical management and counselling, both before and during labour. The detection of spinal position, more than OPP, is predictive of successful delivery. In concordant posterior positions, the labour length, analgesia request, operative delivery, and caesarean section rate are higher than in the other combination. Salvatore Gizzo, Alessandra Andrisani, Marco Noventa, Giorgia Burul, Stefania Di Gangi, Omar Anis, Emanuele Ancona, Donato D'Antona, Giovanni Battista Nardelli, and Guido Ambrosini Copyright © 2014 Salvatore Gizzo et al. All rights reserved. The Evolution of Legislation in the Field of Medically Assisted Reproduction and Embryo Stem Cell Research in European Union Members Thu, 24 Jul 2014 07:18:37 +0000 Medically Assisted Reproduction (MAR), involving in vitro fertilisation (IVF), and research on embryos have created expectation to many people affected by infertility; at the same time it has generated a surplus of laws and ethical and social debates. Undoubtedly, MAR represents a rather new medical field and constant developments in medicine and new opportunities continue to defy the attempt to respond to those questions. In this paper, the authors reviewed the current legislation in the 28 EU member states trying to evaluate the different legislation paths adopted over the last 15 years and highlighting those EU countries with no specific legislation in place and MAR is covered by a general health Law and those countries in which there are no laws in this field but only “guidelines.” The second aim of this work has been to compare MAR legislation and embryo research in EU countries, which derive from different origins ranging from an extremely prohibitive approach versus a liberal one, going through a cautious regulatory approach. Francesco Paolo Busardò, Matteo Gulino, Simona Napoletano, Simona Zaami, and Paola Frati Copyright © 2014 Francesco Paolo Busardò et al. All rights reserved. Applying the Maternal Near Miss Approach for the Evaluation of Quality of Obstetric Care: A Worked Example from a Multicenter Surveillance Study Wed, 23 Jul 2014 12:18:19 +0000 Objective. To assess quality of care of women with severe maternal morbidity and to identify associated factors. Method. This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. The expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. Results. 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (), delays related to quality of medical care (), absence of blood derivatives (), difficulties of communication between health services (), and any delay during the whole process (). Conclusions. This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. In this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care. Samira Maerrawi Haddad, Jose Guilherme Cecatti, Joao Paulo Souza, Maria Helena Sousa, Mary Angela Parpinelli, Maria Laura Costa, Rodolfo C. Pacagnella, Ione R. Brum, Olímpio B. Moraes Filho, Francisco E. Feitosa, Carlos A. Menezes, Everardo M. Guanabara, Joaquim L. Moreira, Frederico A. Peret, Luiza E. Schmaltz, Leila Katz, Antonio C. Barbosa Lima, Melania M. Amorim, Marilia G. Martins, Denis J. Nascimento, Cláudio S. Paiva, Roger D. Rohloff, Sergio M. Costa, Adriana G. Luz, Gustavo Lobato, Eduardo Cordioli, Jose C. Peraçoli, Nelson L. Maia Filho, Silvana M. Quintana, Fátima A. Lotufo, Carla B. Andreucci, Márcia M. Aquino, and Rosiane Mattar Copyright © 2014 Samira Maerrawi Haddad et al. All rights reserved. BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management Tue, 22 Jul 2014 11:48:21 +0000 Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers. Giulia Girolimetti, Anna Myriam Perrone, Donatella Santini, Elena Barbieri, Flora Guerra, Simona Ferrari, Claudio Zamagni, Pierandrea De Iaco, Giuseppe Gasparre, and Daniela Turchetti Copyright © 2014 Giulia Girolimetti et al. All rights reserved. Management of Poor Responders in IVF: Is There Anything New? Sun, 20 Jul 2014 07:13:46 +0000 Despite the fact that in the last two decades an enormous number of papers on the topic of poor ovarian response have been published in the literature, so far it has been impossible to identify any efficient treatment to improve the ovarian response and the clinical outcome of this group of patients. The incidence of poor ovarian responders among infertile women has been estimated at 9–24% but according to recent reviews, it seems to have slightly increased. The limitation in quantifying the incidence of these patients among the infertile population is due to the difficulty of a clear definition in literature. A recent paper by the Bologna ESHRE working group on poor ovarian response has been the first real attempt to find a common definition. Current literature proposes new risk factors which could be the cause of a reduction in ovarian reserve, which also includes genetic factors. This represents the first necessary step towards finding applicable solutions for these patients. To date, there is a substantial lack of literature that identifies an ideal protocol for these patients. The use of the “Bologna criteria” and the introduction of long acting gonadotropin in clinical practice have given rise to new promising stimulation protocols for this group of patients. Filippo Ubaldi, Alberto Vaiarelli, Rosario D’Anna, and Laura Rienzi Copyright © 2014 Filippo Ubaldi et al. All rights reserved. Expression and Clinical Significance of the Autophagy Proteins BECLIN 1 and LC3 in Ovarian Cancer Thu, 17 Jul 2014 08:24:29 +0000 Autophagy is dysregulated in cancer and might be involved in ovarian carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k class III, plays a critical role in the regulation of both autophagy and cell death. Induction of autophagy is associated with the presence of vacuoles characteristically labelled with the protein LC3. We have studied the biological and clinical significance of BECLIN 1 and LC3 in ovary tumours of different histological types. The positive expression of BECLIN 1 was well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of BCL-2. The latter inhibits the autophagy function of BECLIN 1. We found that type I tumours, which are less aggressive than type II, were more frequently expressing high level of BECLIN 1. Of note, tumours of histologic grade III expressed low level of BECLIN 1. Consistently, high level of expression of BECLIN 1 and LC3 in tumours is well correlated with the overall survival of the patients. The present data are compatible with the hypotheses that a low level of autophagy favours cancer progression and that ovary cancer with upregulated autophagy has a less aggressive behaviour and is more responsive to chemotherapy. Guido Valente, Federica Morani, Giuseppina Nicotra, Nicola Fusco, Claudia Peracchio, Rossella Titone, Oscar Alabiso, Riccardo Arisio, Dyonissios Katsaros, Chiara Benedetto, and Ciro Isidoro Copyright © 2014 Guido Valente et al. All rights reserved. Pharmaceutical Options for Triggering of Final Oocyte Maturation in ART Tue, 15 Jul 2014 09:07:35 +0000 Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages over hCG trigger. GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle surge of gonadotropins, without the prolonged action of hCG, resulting in the retrieval of more mature oocytes and a significant reduction in or elimination of OHSS as compared to hCG triggering. The induction of final follicular maturation using GnRHa represents a paradigm shift in the ovulation triggering concept in ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key central regulators of the neuroendocrine mechanisms of human reproduction, who have been shown to effectively elicit an LH surge and to induce final oocyte maturation in IVF cycles. This new trigger concept may, therefore, offer a completely new, “natural” pharmacological option for ovulation induction. Whether kisspeptins will be the future agent to trigger ovulation remains to be further explored. Juan Carlos Castillo, Peter Humaidan, and Rafael Bernabéu Copyright © 2014 Juan Carlos Castillo et al. All rights reserved. Visualization of Polypropylene and Polyvinylidene Fluoride Slings in Perineal Ultrasound and Correlation with Clinical Outcome Sun, 13 Jul 2014 09:27:47 +0000 Introduction and Hypothesis. Complications and malfunctioning after TOT can occur due to several factors, such as the material of the sling. The aim of the present study is to evaluate morphology and functionality of two types of slings (PVDF; polypropylene) in vivo using perineal ultrasound (PUS). Materials. In women with TOT four criteria for PUS were taken and checked for possible differences: vertical stability of the sling position during Valsalva manoeuvre and contraction; distance “sling to urethra”; width of the sling and condition of the selvedges. Results. We observed an increased vertical displacement of the PP-slings, a significantly smaller variance to the extent of the displacement in PVDF-slings (), a significantly larger distance between sling and urethra () in PVDF-slings, and a significantly smaller width of the PP-slings (). Conclusion. Significant differences were found between the slings according to the four criteria. There was no difference established between the slings in the improvement of continence and no significant influence of the parameters was found for the resulting state of continence. In future studies, PUS may help to link differences in the morphology and functionality of in vivo slings to their material properties. Laila Najjari, Julia Hennemann, Ruth Kirschner-Hermanns, Nicolai Maass, and Thomas Papathemelis Copyright © 2014 Laila Najjari et al. All rights reserved. Biomarkers in Women’s Cancers, Gynecology, and Obstetrics Thu, 10 Jul 2014 12:47:00 +0000 Peter A. Fasching, Gottfried E. Konecny, and Amanda B. Spurdle Copyright © 2014 Peter A. Fasching et al. All rights reserved. Unique Pattern of Component Gene Disruption in the NRF2 Inhibitor KEAP1/CUL3/RBX1 E3-Ubiquitin Ligase Complex in Serous Ovarian Cancer Wed, 09 Jul 2014 00:00:00 +0000 The NFE2-related factor 2 (NRF2) pathway is critical to initiate responses to oxidative stress; however, constitutive activation occurs in different cancer types, including serous ovarian carcinomas (OVCA). The KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex is a regulator of NRF2 levels. Hence, we investigated the DNA-level mechanisms affecting these genes in OVCA. DNA copy-number loss (CNL), promoter hypermethylation, mRNA expression, and sequence mutation for KEAP1, CUL3, and RBX1 were assessed in a cohort of 568 OVCA from The Cancer Genome Atlas. Almost 90% of cases exhibited loss-of-function alterations in any components of the NRF2 inhibitory complex. CNL is the most prominent mechanism of component disruption, with RBX1 being the most frequently disrupted component. These alterations were associated with reduced mRNA expression of complex components, and NRF2 target gene expression was positively enriched in 90% of samples harboring altered complex components. Disruption occurs through a unique DNA-level alteration pattern in OVCA. We conclude that a remarkably high frequency of DNA and mRNA alterations affects components of the KEAP1/CUL3/RBX1 complex, through a unique pattern of genetic mechanisms. Together, these results suggest a key role for the KEAP1/CUL3/RBX1 complex and NRF2 pathway deregulation in OVCA. Victor D. Martinez, Emily A. Vucic, Kelsie L. Thu, Larissa A. Pikor, Roland Hubaux, and Wan L. Lam Copyright © 2014 Victor D. Martinez et al. All rights reserved. Neurobiological Mechanisms of Pelvic Pain Tue, 08 Jul 2014 08:55:29 +0000 Pelvic pain is a common condition which significantly deteriorates health-related quality of life. The most commonly identified causes of pain in the pelvic region are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal. However, in up to 33% of patients the source of this symptom is not identified, frustrating both patients and health-care professionals. Pelvic pain may involve both the somatic and visceral systems, making the differential diagnosing challenging. This paper aimed to review the mechanisms involved in pelvic pain perception by analyzing the neural plasticity and molecules which are involved in these complex circuits. Massimo Origoni, Umberto Leone Roberti Maggiore, Stefano Salvatore, and Massimo Candiani Copyright © 2014 Massimo Origoni et al. All rights reserved. Predictors of Size for Gestational Age in St. Louis City and County Mon, 07 Jul 2014 11:12:48 +0000 Objective. To identify social, behavioral, and physiological risk factors associated with small for gestational age (SGA) by gestational age category in St. Louis City and County. Methods. A retrospective cohort study was conducted using birth certificate and fetal death records from 2000 to 2009 (n = 142,017). Adjusted associations of risk factors with SGA were explored using bivariate logistic regression. Four separate multivariable logistic regression analyses, stratified by gestational age, were conducted to estimate adjusted odds ratios. Results. Preeclampsia and inadequate weight gain contributed significantly to increased odds for SGA across all gestational age categories. The point estimates ranged from a 3.41 increased odds among women with preeclampsia and 1.76 for women with inadequate weight gain at 24–28 weeks’ gestational age to 2.19 and 2.11 for full-term infants, respectively. Among full-term infants, smoking (aOR = 2.08), chronic hypertension (aOR = 1.46), and inadequate prenatal care (aOR = 1.25) had the next most robust and significant impact on SGA. Conclusion. Preeclampsia and inadequate weight gain are significant risk factors for SGA, regardless of gestational age. Education on the importance of nutrition and adequate weight gain during pregnancy is vital. In this community, disparities in SGA and smoking rates are important considerations for interventions designed to improve birth outcomes. Pamela K. Xaverius, Joanne Salas, Candice L. Woolfolk, Frances Leung, Jessica Yuan, and Jen Jen Chang Copyright © 2014 Pamela K. Xaverius et al. All rights reserved. Detection of Single Umbilical Artery in the First Trimester Ultrasound: Its Value as a Marker of Fetal Malformation Thu, 03 Jul 2014 00:00:00 +0000 Introduction. The value of a single umbilical artery (SUA) in first trimester ultrasound is not well established. The aim of our study was to determinate the relevance of diagnosis of single umbilical artery in first trimester ultrasound as an early marker suggesting the presence of malformations or associated chromosomopathies. Material and Methods. Retrospective study of clinical cases of SUA diagnosed at the University Hospital Puerta de Hierro in Madrid (Spain) during the first trimester ultrasound between September 2008 and September 2012. Results. Prevalence of SUA was 1.1% in single pregnancies and 3.3% in twin pregnancies. Sensitivity, specificity, false positive rate, and false negative rate for the finding in the first trimester were 84.2, 99.8, 0.2, and 15.7%, respectively. 17.6% of cases had associated malformations. With an ultrasound in the 16th week most of the cases with significant fetal malformation were diagnosed. Discussion. SUA is a useful marker in the first trimester for fetal malformation pathology, as it will allow detecting a large number of cases with malformations before 20 weeks of gestation. Cristina Martínez-Payo, Elena Cabezas, Yolanda Nieto, Miguel Ruiz de Azúa, Fátima García-Benasach, and Enrique Iglesias Copyright © 2014 Cristina Martínez-Payo et al. All rights reserved. Phytochemicals: A Multitargeted Approach to Gynecologic Cancer Therapy Tue, 01 Jul 2014 07:14:27 +0000 Gynecologic cancers constitute the fourth most common cancer type in women. Treatment outcomes are dictated by a multitude of factors, including stage at diagnosis, tissue type, and overall health of the patient. Current therapeutic options include surgery, radiotherapy, and chemotherapy, although significant unmet medical needs remain in regard to side effects and long-term survival. The efficacy of chemotherapy is influenced by cellular events such as the overexpression of oncogenes and downregulation of tumor suppressors, which together determine apoptotic responses. Phytochemicals are a broad class of natural compounds derived from plants, a number of which exhibit useful bioactive effects toward these pathways. High-throughput screening methods, rational modification, and developments in regulatory policies will accelerate the development of novel therapeutics based on these compounds, which will likely improve overall survival and quality of life for patients. Lee Farrand, Se-Woong Oh, Yong Sang Song, and Benjamin K. Tsang Copyright © 2014 Lee Farrand et al. All rights reserved. Value of Histopathologic Examination of Uterine Products after First-Trimester Miscarriage Thu, 26 Jun 2014 06:06:12 +0000 The main rationale of routine histopathologic examination of products after first-trimester miscarriages is to detect an ectopic pregnancy or a molar pregnancy, which require further management. An alternative approach is to examine the products only when there is a definite indication. As there is no agreement, we aimed to study whether routine histopathological examination of tissues obtained after first-trimester miscarriage is of any clinical value in our populations. Medical records of all (558) patients with a diagnosis of first-trimester miscarriage over 4 years (2007–2010) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were reviewed. Histopathologic examination confirmed products of conception in 537 (96.2%) patients, no products of conception in 17 (3%) patients, molar pregnancy in 2 (0.4%) patients, and decidual tissues without chorionic villi (Arias-Stella reaction) in 2 (0.4%) patients. After clinical correlation, only one unsuspected partial molar pregnancy was diagnosed by histopathology examination. Conclusion is that it does not appear reasonable to perform histopathological examination routinely after all first-trimester miscarriages in our studied population. We recommend that histopathological examination be performed in select instances: when the diagnosis is uncertain, when fewer tissues have been obtained during surgery, when unexpected pathology was seen, when ultrasound suggests a molar pregnancy, or when patients are considered at high risk for trophoblastic disease. Sharifa Ali Alsibiani Copyright © 2014 Sharifa Ali Alsibiani. All rights reserved. Using Adhesive Glue to Repair First Degree Perineal Tears: A Prospective Randomized Controlled Trial Thu, 26 Jun 2014 00:00:00 +0000 Our objective was to evaluate the effectiveness of adhesive glue in repairing first degree perineal tears. We conducted a noninferiority prospective, randomized, controlled trial comparing adhesive glue with traditional suturing. Each case was evaluated immediately after birth and after the puerperium. The two-sample t-test and the Mann-Whitney nonparametric test were applied to compare quantitative variables between the treatment groups. The chi-squared test and Fisher's exact test were used to assess the association between qualitative variables. A total of 102 women participated, 28 in the suture arm and 74 in the adhesive glue arm. While cosmetic and functional results of adhesive glue use were not inferior to suturing, the use of adhesive glue was associated with a shorter procedure, less need for local anesthetic, less pain, and greater satisfaction. Our results suggest a novel approach for the repair of common postpartum first degree lacerations. The use of adhesive glue achieves cosmetic and functional results equal to traditional suturing and offers some immediate advantages for the patient. While further clinical trials are needed to validate our results, it is important to inform obstetrician of the possible use of adhesive glue in these very common clinical scenarios. This trial is registered with NCT00746707. Tomer Feigenberg, Esther Maor-Sagie, Einat Zivi, Mushira Abu-Dia, Assaf Ben-Meir, Hen Y. Sela, and Yossef Ezra Copyright © 2014 Tomer Feigenberg et al. All rights reserved. Antiangiogenesis Therapy of Endometriosis Using PAMAM as a Gene Vector in a Noninvasive Animal Model Tue, 24 Jun 2014 12:10:19 +0000 Objective. To evaluate the characteristics and antiangiogenic effects of endostatin-loaded PAMAM on endometriosis in a noninvasive animal model. Materials and Methods. A noninvasive animal model was established by injecting adenovirus-GFP transfected endometrial stromal and glandular epithelial cells subcutaneously into nude mice. Endostatin-loaded PAMAM was prepared and identified by transmission electron microscopy. For in vitro studies, the DNA protection and cytotoxicity of PAMAM were investigated and compared with Lipofectamine 2000. For in vivo study, endostatin-loaded PAMAM was injected into the noninvasive model and evaluated by continuously observing the fluorescent lesion, lesion weight, microvessel density and VEGF immunostaining. Results. Compared with Lipofectamine 2000, PAMAM and HC PAMAM-ES group, MC PAMAM-ES group and LC PAMAM-ES group demonstrated a better stromal cells protective such that MC PAMAM-ES group of CCK8 was 0.617 ± 0.122 at 24 hr and 0.668 ± 0.143 at 48 hr and LC PAMAM-ES group of CCK8 was 0.499 ± 0.103 at 24 hr and 0.610 ± 0.080 at 48 hr in stromal cells () but similar cytotoxicity in glandular epithelial cells in vitro. After 16 hrs of digestion, DNA decreased slightly under the protection of PAMAM. Endostatin-loaded PAMAM of HD PAMAM-ES group and LD PAMAM-ES group inhibited the growth of the endometriotic lesion in vivo at days 15, 20, 25 and 30 detected by noninvasive observation after injecting one dose endostatin of various medicines into the endometrial lesion in each mouse on day 10 () and confirmed by lesion weight at day 30 with HD PAMAM-ES group being 0.0104 ± 0.0077 g and LD PAMAM-ES group being 0.0140 ± 0.0097 g (). Immunohistochemistry results showed that endostatin-loaded PAMAM reduced the microvessel density 3.8 ± 2.4 especially in HD PAMAM-ES group in the lesion (). Conclusion. Endostatin-loaded PAMAM inhibits the development of endometriosis through an antiangiogenic mechanism and can be observed through the noninvasive endometriosis model. Ningning Wang, Bin Liu, Lili Liang, Yanxin Wu, Hongzhe Xie, Jiaming Huang, Xu Guo, Jinfeng Tan, Xuejun Zhan, Yongdong Liu, Liantang Wang, and Peiqi Ke Copyright © 2014 Ningning Wang et al. All rights reserved. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer Tue, 24 Jun 2014 05:37:35 +0000 Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed. Tae Hun Kim, Dong Hoon Suh, Mi-Kyung Kim, and Yong Sang Song Copyright © 2014 Tae Hun Kim et al. All rights reserved. Prenatal Ultrasound Screening for External Ear Abnormality in the Fetuses Mon, 23 Jun 2014 07:48:20 +0000 Objectives. To investigate the best time of examination and section chosen of routine prenatal ultrasound screening for external ear abnormalities and evaluate the feasibility of examining the fetal external ear with ultrasonography. Methods. From July 2010 until August 2011, 42118 pregnant women with single fetus during 16–40 weeks of pregnancy were enrolled in the study. Fetal auricles and external auditory canal in the second trimester of pregnancy were evaluated by routine color Doppler ultrasound screening and systematic screening. Ultrasound images of fetal external ears were obtained on transverse-incline view at cervical vertebra level and mandible level and on parasagittal view and coronal view at external ear level. Results. Five fetuses had anomalous ears including bilateral malformed auricles with malformed external auditory canal, unilateral deformed external ear, and unilateral microtia. The detection rate of both auricles was negatively correlated with gestational age. Of the 5843 fetuses undergoing a routine ultrasound screening, 5797 (99.21%) had bilateral auricles. Of the 4955 fetuses following systematic screening, all fetuses (100%) had bilateral auricles. The best time for fetal auricles observation with ultrasonography is 20–24 weeks of pregnancy. Conclusions. Detection of external ear abnormalities may assist in the diagnosis of chromosomal abnormalities. Jun Wei, Suzhen Ran, Zhengchun Yang, Yun Lin, Jing Tang, and Haitao Ran Copyright © 2014 Jun Wei et al. All rights reserved. Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas Sun, 22 Jun 2014 07:17:38 +0000 In this study the expression of GnRH, FSH, LH, ER-α, ER-β, and PR receptors was examined in uterine myomas of women in reproductive and perimenopausal age. In cases of GnRH and tropic hormones a membranous and cytoplasmic immunohistochemical reaction was detected, in cases of ER-α and PR the reaction was located in cell nucleus, and in the case of ER-β it manifested also a cytoplasmic location. In some of the examined cases the expression was detected in endometrium, myocytes, and endothelium of blood vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and LH receptors increases with age, whereas the level of progesterone and both estrogen receptors decreases. In myomas of women in reproductive age, independently of their size, expression of GnRH, FSH, and LH receptors was more pronounced than in myometrium. In women of perimenopausal age, independently of myoma size, expression of LH and estrogen α receptors was higher while expression of GnRH receptors was lower than in myometrium. FSH receptor expression was not observed. Expression of estrogen receptor β was not affected by age of the woman or size of myoma. Analysis of obtained results indicates on existing in small myomas local feedback axis between GnRH-LH-progesterone. Danuta Plewka, Jacek Marczyński, Michał Morek, Edyta Bogunia, and Andrzej Plewka Copyright © 2014 Danuta Plewka et al. All rights reserved. Are Mood and Anxiety Disorders and Alexithymia Associated with Endometriosis? A Preliminary Study Sun, 22 Jun 2014 00:00:00 +0000 Objective. The aim of this preliminary study was to determine whether psychiatric disorders, psychopathological symptoms, and alexithymia are associated with endometriosis in an Italian population. Study Design. A preliminary study comprising 37 Italian patients with surgically confirmed endometriosis and 43 controls, without clinical and ultrasound signs of endometriosis, was carried out. Both patients and controls were evaluated for the presence/absence of psychiatric disorders, psychopathological symptoms, alexithymia, and pain symptoms (nonmenstrual pelvic pain, dysmenorrhea, and dyspareunia). Results. Statistically significant differences were found between cases and controls for prevalence of mood and anxiety disorders, malfunctioning on obsessive-compulsive subscale () and depression subscale () of the Symptom Checklist-90-Revisited (SCL-90-R), and higher alexithymia levels (). Patients with endometriosis-associated pain showed greater prevalence of psychiatric disorders compared to pain-free patients but that difference was not significant. Significant correlation was found between malfunctioning in some SCL-90-R dimensions and pelvic pain, dysmenorrhea, and dyspareunia scores at the visual analog score (VAS). Conclusion. Some psychopathological aspects, such as psychoemotional distress and alexithymia, are more frequent in women with endometriosis and might amplify pain symptoms in these patients. Gabriele Cavaggioni, Claudia Lia, Serena Resta, Tatiana Antonielli, Pierluigi Benedetti Panici, Francesca Megiorni, and Maria Grazia Porpora Copyright © 2014 Gabriele Cavaggioni et al. All rights reserved. New Advances in Reproductive Biomedicine Wed, 18 Jun 2014 08:14:32 +0000 Irma Virant-Klun, Jeroen Krijgsveld, John Huntriss, and Raymond J. Rodgers Copyright © 2014 Irma Virant-Klun et al. All rights reserved. Widespread 25-Hydroxyvitamin D Deficiency in Affluent and Nonaffluent Pregnant Indian Women Wed, 18 Jun 2014 07:17:10 +0000 Objectives. This cross-sectional study primarily aimed to assess vitamin D adequacy in the third trimester of pregnancy using 25-hydroxyvitamin D (25(OH)D) and explore lifestyle characteristics (sun exposure index, diet, and economic indicators) associated with serum 25(OH)D. The secondary aim was to examine the relationship of serum 25(OH)D with birth weight and gestational age. Methods. Serum 25(OH)D was measured by chemiluminescent immunoassay in 150 pregnant women from Mumbai. Sun exposure index was computed. Dietary calcium, phytate : calcium ratio, and dietary phosphorus was calculated using the 24-hour diet recall method. Results. All women had 25(OH)D levels < 30.00 ng/ml. Multivariable linear regression showed that nonaffluent women had poorer 25(OH)D status than their affluent counterparts (; ). Higher sun exposure index was associated with higher 25(OH)D concentrations (; ), which remained significant after controlling for covariates. At the bivariate level, mothers of infants weighing <2500 g had lower serum 25(OH)D concentrations compared to mothers whose infants weighed 2500 g (). This association became non-significant after controlling for covariates. Conclusions. Vitamin D deficiency was universally prevalent in the cohort studied. There is a need to develop culturally sensitive strategies for improving the 25(OH)D status. Rati Jani, Suhaila Palekar, Tanya Munipally, Padmini Ghugre, and Shobha Udipi Copyright © 2014 Rati Jani et al. All rights reserved. Regulation of Mitochondrial Genome Inheritance by Autophagy and Ubiquitin-Proteasome System: Implications for Health, Fitness, and Fertility Tue, 17 Jun 2014 07:07:38 +0000 Mitochondria, the energy-generating organelles, play a role in numerous cellular functions including adenosine triphosphate (ATP) production, cellular homeostasis, and apoptosis. Maternal inheritance of mitochondria and mitochondrial DNA (mtDNA) is universally observed in humans and most animals. In general, high levels of mitochondrial heteroplasmy might contribute to a detrimental effect on fitness and disease resistance. Therefore, a disposal of the sperm-derived mitochondria inside fertilized oocytes assures normal preimplantation embryo development. Here we summarize the current research and knowledge concerning the role of autophagic pathway and ubiquitin-proteasome-dependent proteolysis in sperm mitophagy in mammals, including humans. Current data indicate that sperm mitophagy inside the fertilized oocyte could occur along multiple degradation routes converging on autophagic clearance of paternal mitochondria. The influence of assisted reproductive therapies (ART) such as intracytoplasmic sperm injection (ICSI), mitochondrial replacement (MR), and assisted fertilization of oocytes from patients of advanced reproductive age on mitochondrial function, inheritance, and fitness and for the development and health of ART babies will be of particular interest to clinical audiences. Altogether, the study of sperm mitophagy after fertilization has implications in the timing of evolution and developmental and reproductive biology and in human health, fitness, and management of mitochondrial disease. Won-Hee Song, John William Oman Ballard, Young-Joo Yi, and Peter Sutovsky Copyright © 2014 Won-Hee Song et al. All rights reserved. Very Low Birth Weight and Perinatal Periods of Risk: Disparities in St. Louis Sun, 15 Jun 2014 11:47:01 +0000 Objective. Very low birth weight (VLBW) is a significant issue in St. Louis, Missouri. Our study evaluated risk factors associated with VLBW in this predominantly urban community. Methods. From 2000 to 2009, birth and fetal death certificates were evaluated (), and mortality rates were calculated for perinatal periods of risk. The Kitagawa method was used to explore fetoinfant mortality rates (FIMR) in terms of birth weight distribution and birthweight specific mortality. Multivariable logistic regression was used to assess the magnitude of association of selected risk factors with VLBW. Results. VLBW contributes to 50% of the excess FIMR in St. Louis City and County. The highest proportion of VLBW can be attributed to black maternal race (40.6%) in St. Louis City, inadequate prenatal care (19.8%), and gestational hypertension (12.0%) among black women. Medicaid was found to have a protective effect for VLBW among black women (population attributable risk (PAR) = −14.5). Discussion. Interventions targeting the health of women before and during conception may be most successful at reducing the disparities in VLBW in this population. Interventions geared towards smoking cessation and improvements in Medicaid and prenatal care access for black mothers and St. Louis City residents can greatly reduce VLBW rates. Pamela Xaverius, Joanne Salas, Deborah Kiel, and Candice Woolfolk Copyright © 2014 Pamela Xaverius et al. All rights reserved. Follicular Fluid Oocyte/Cumulus-Free DNA Concentrations as a Potential Biomolecular Marker of Embryo Quality and IVF Outcome Sun, 15 Jun 2014 11:43:11 +0000 The present prospective study examined the follicular fluid oocyte/cumulus-free DNA concentrations (ff o/c-free DNA) during ovarian stimulation and the possible association between ff o/c-free DNA and embryological results such as embryo quality and pregnancy rate. Eighty-three women undergoing IV/ICSI-ET treatments were prospectively included in this study. ff o/c-free DNA was determined by conventional quantitative real time PCR-Sybr green detection approach. The 83 ff samples were categorized in two groups: group 1 with cumulus oocytes complexes (CoCs) and group 2 with CoCs = 1. Group 1 revealed significant higher embryo quality in terms of mean score of embryo transfer (MSET), but lower ff o/c-free DNA concentrations compared to group 2. The two groups showed comparable pregnancy rates (positive hCG and clinical pregnancy). The higher the ff o/c-free DNA concentration, the lower the number of produced oocytes. ff o/c-free DNA did not seem to have any direct role in the IVF outcome. Further research is required to clarify whether ff o/c-free DNA is a biomolecular marker of embryo quality and IVF outcome. M. Dimopoulou, G. Anifandis, C. I. Messini, K. Dafopoulos, S. Kouris, S. Sotiriou, M. Satra, N. Vamvakopoulos, and I. E. Messinis Copyright © 2014 M. Dimopoulou et al. All rights reserved. Preconception Screening for Cytomegalovirus: An Effective Preventive Approach Thu, 12 Jun 2014 05:56:20 +0000 Congenital cytomegalovirus (CMV) is the leading infectious cause of sensorineural hearing loss and delayed psychomotor development. Viral transmission to the fetus is far more likely to occur following a primary than a secondary maternal infection. Primary prevention seems to be the best means to reduce the burden of congenital CMV due to the lack of treatment options during pregnancy. We evaluated this approach on a cohort of 500 women planning pregnancy who attended our fertility clinic. Of the 444 who underwent CMV screening, 18 (4.1%) had positive IgM serology for CMV; of these, IgG avidity was high in 12 (remote infection) and low in 6 (recent infection). The latter were advised to delay pregnancy. All women who were seroimmune for CMV (366/444, 82.4%), including the 12 with remote infection, continued fertility treatment. The remaining patients (72/444, 16.2%), who were not immune to CMV at the initial screen, were advised to minimize CMV exposure by improving personal hygiene and to continue fertility treatment. None of the 69/72 (95.8%) women who were followed for one year were infected with CMV. Cytomegalovirus testing and counselling at preconception seemed effective in reducing CMV exposure in pregnancy. Orna Reichman, Ian Miskin, Limor Sharoni, Talia Eldar-Geva, Doron Goldberg, Avi Tsafrir, and Michael Gal Copyright © 2014 Orna Reichman et al. All rights reserved. Analyzing Association of the XRCC3 Gene Polymorphism with Ovarian Cancer Risk Tue, 10 Jun 2014 04:57:59 +0000 This meta-analysis aims to examine whether the XRCC3 polymorphisms are associated with ovarian cancer risk. Eligible case-control studies were identified through search in PubMed. Pooled odds ratios (ORs) were appropriately derived from fixed effects models. We therefore performed a meta-analysis of 5,302 ovarian cancer cases and 8,075 controls from 4 published articles and 8 case-control studies for 3 SNPs of XRCC3. No statistically significant associations between XRCC3 rs861539 polymorphisms and ovarian cancer risk were observed in any genetic models. For XRCC3 rs1799794 polymorphisms, we observed a statistically significant correlation with ovarian cancer risk using the homozygote comparison (T2T2 versus T1T1: OR = 0.70, 95% CI = 0.54–0.90, ), heterozygote comparison (T1T2 versus T1T1: OR = 1.10, 95% CI = 1.00–1.21, ), and the recessive genetic model (T2T2 versus T1T1+T1T2: OR = 0.67, 95% CI = 0.52–0.87, ). For XRCC3 rs1799796 polymorphisms, we also observed a statistically significant correlation with ovarian cancer risk using the heterozygote comparison (T1T2 versus T1T1: OR = 0.91, 95% CI = 0.83–0.99, ). In conclusion, this meta-analysis shows that the XRCC3 were associated with ovarian cancer risk overall for Caucasians. Asian and African populations should be further studied. Cunzhong Yuan, Xiaoyan Liu, Shi Yan, Cunfang Wang, and Beihua Kong Copyright © 2014 Cunzhong Yuan et al. All rights reserved. Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12) and Omega-3 Fatty Acids Mon, 09 Jun 2014 11:49:11 +0000 We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. Vinita Khot, Anvita Kale, Asmita Joshi, Preeti Chavan-Gautam, and Sadhana Joshi Copyright © 2014 Vinita Khot et al. All rights reserved. Older Women’s Sexual Desire Problems: Biopsychosocial Factors Impacting Them and Barriers to Their Clinical Assessment Thu, 05 Jun 2014 11:11:31 +0000 Sexual desire is a major component of sexuality at any age, and inhibited desire is one of the main sexual dysfunctions reported by older women. Nonetheless, in medical settings, for a variety of reasons discussed herein, its assessment—as well as the assessment of older women’s sexual health in general—is typically avoided or conducted by asking a single sex question. In this paper, we have reviewed the literature (most of which is preliminary in nature) regarding the main psychosocial and health factors that could impact older women’s sexual desire, as well as potential obstacles to the assessment and treatment of this geriatric sexual issue. It is certainly advisable that medical care providers who are uncomfortable discussing older women’s sexual concerns be prepared to make appropriate referrals to clinicians who possess the proper training to accurately assess and treat sexual challenges (and female sexual interest problems in particular) in this neglected patient population. Michelle Maciel and Luciana Laganà Copyright © 2014 Michelle Maciel and Luciana Laganà. All rights reserved. Breastfeeding Duration: A Survival Analysis—Data from a Regional Immunization Survey Wed, 04 Jun 2014 07:04:28 +0000 Objective. To report the duration of and factors associated with exclusive and any breastfeeding among the French-speaking community of Belgium (Wallonia). Material and Methods. A two-stage cluster sample was drawn from the population of children aged 18–24 months living in the area in 2012. Anamnestic data on breastfeeding and sociodemographic information were collected from 525 mothers. Cox’s proportional hazards model was used to identify factors associated with discontinuing breastfeeding. Results and Discussion. Only 35.1% of the women were satisfied with their duration of any breastfeeding. At 3 months, 54.1% of the infants were breastfed, of which 40.6% exclusively, with these percentages falling to 29.1% and 12.6% at 6 months. Exclusive and any breastfeeding durations were independently positively associated () with foreign-born mothers, awareness of WHO recommendations, and maternity leave >3 months. Exclusive BF duration was associated with higher parental income and the prenatal decision to breastfeed. The duration of any breastfeeding was associated with the mothers’ age of ≥30 years and whether they were exclusively breastfeeding at discharge from the maternity unit. Conclusions. Programs promoting and supporting BF should concentrate on training prenatal health-care professionals. Prenatal professional advice may promote adherence to WHO BF guidelines. The benefits of exclusive BF should be emphasized. Pregnant women should be discouraged from introducing supplementary feeding in the maternity ward. E. Robert, Y. Coppieters, B. Swennen, and M. Dramaix Copyright © 2014 E. Robert et al. All rights reserved. A Risk-Scoring Model for the Prediction of Endometrial Cancer among Symptomatic Postmenopausal Women with Endometrial Thickness > 4 mm Tue, 03 Jun 2014 07:05:32 +0000 Objective. To develop and test a risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women at risk of intrauterine malignancy. Methods. We prospectively studied 624 postmenopausal women with vaginal bleeding and endometrial thickness > 4 mm undergoing diagnostic hysteroscopy. Patient characteristics and endometrial assessment of women with or without endometrial cancer were compared. Then, a risk-scoring model, including the best predictors of endometrial cancer, was tested. Univariate, multivariate, and ROC curve analysis were performed. Finally, a split-sampling internal validation was also performed. Results. The best predictors of endometrial cancer were recurrent vaginal bleeding (odds ratio ), the presence of hypertension endometrial thickness > 8 mm , and age > 65 years . These variables were used to create a risk-scoring model (RHEA risk-model) for the prediction of intrauterine malignancy, with an area under the curve of 0.878 (95% CI 0.842 to 0.908; ). At the best cut-off value (score ≥ 4), sensitivity and specificity were 87.5% and 80.1%, respectively. Conclusion. Among symptomatic postmenopausal women with endometrial thickness > 4 mm, a risk-scoring model including patient characteristics and endometrial thickness showed a moderate diagnostic accuracy in discriminating women with or without endometrial cancer. Based on this model, a decision algorithm was developed for the management of such a population. Luca Giannella, Kabala Mfuta, Tiziano Setti, Lillo Bruno Cerami, Ezio Bergamini, and Fausto Boselli Copyright © 2014 Luca Giannella et al. All rights reserved. Provincial Maternal Mortality Surveillance Systems in China Tue, 03 Jun 2014 07:03:35 +0000 Background. Provincial maternal mortality surveillance systems (PMMSS) have been set up in nearly all the provinces in China to monitor local maternal mortality and provide the evidence for maternal health interventions suited to local conditions. However, till now little is known outside of China about the characteristics of PMMSS. Methods. A systematic review of the literature contained in PubMed and China Academic Journal Network Publishing database was carried out. The current situation on PMMSS was described. Provincial disparities on PMMR in six provinces were analyzed by Poisson regression analysis. Results. A total of 35 studies met the inclusion criteria, of which 31 were published in Chinese. PMMSS were set up and adjusted by the provincial government based on their own financial resources and demand. Provinces from remote region had the highest risk of maternal mortality, followed by provinces from inland region and coast region. Conclusions. PMMSS may be the most reliable data source for measuring provincial level MMR in each province. Great provincial disparities on PMMSS and PMMR do exist within the country; more emphasis should be placed on improving PMMSS and reducing PMMR particularly in the provinces with high maternal death burden. Xiao-Ling Gan, Chang-Lai Hao, Xiao-Jing Dong, Sophie Alexander, Michèle Wilmet Dramaix, Li-Na Hu, and Wei-Hong Zhang Copyright © 2014 Xiao-Ling Gan et al. All rights reserved. Endometriosis Patients in the Postmenopausal Period: Pre- and Postmenopausal Factors Influencing Postmenopausal Health Mon, 02 Jun 2014 00:00:00 +0000 Objective. To evaluate patients’ health status and the course of endometriosis from the premenopausal to the postmenopausal period and evaluate influencing factors that may be relevant. Methods. Questionnaire completed by 35 postmenopausal women in whom endometriosis had been histologically confirmed premenopausally. Correlation and regression analyses were carried out to identify factors relevant to their postmenopausal health status. Results. Overall, there was clear improvement in typical endometriosis symptoms and sexual life. Clear associations () were observed between premenopausal factors like physical limitations caused by the disease, impaired social contacts and psychological problems, and postmenopausal pain and impairment of sexual life. Three statistical models for assessing pain and impairment of sexual life in the postmenopausal period were calculated on the basis of clinical symptoms in the premenopausal period, with a very high degree of accuracy (; = 0.833/0.857/0.931). Conclusions. The results of the survey strongly suggest that physical fitness and freedom from physical restrictions, a good social environment, and psychological care in both the premenopausal and postmenopausal periods lead to marked improvements in the postmenopausal period with regard to pain, dyspareunia, and influence on sexual life in endometriosis patients. Dietmar Haas, Peter Wurm, Wolfgang Schimetta, Kathrin Schabetsberger, Andreas Shamiyeh, Peter Oppelt, and Helge Binder Copyright © 2014 Dietmar Haas et al. All rights reserved. Single Amino Acid Arginine Deprivation Triggers Prosurvival Autophagic Response in Ovarian Carcinoma SKOV3 Sun, 01 Jun 2014 06:33:14 +0000 Autophagy is a process of cytosol-to-lysosome vesicle trafficking of cellular constituents for degradation and recycling of their building blocks. Autophagy becomes very important for cell viability under different stress conditions, in particular under amino acid limitation. In this report we demonstrate that single amino acid arginine deprivation triggers profound prosurvival autophagic response in cultured human ovarian cancer SKOV3 cells. In fact, a significant drop in viability of arginine-starved SKOV3 cells was observed when autophagy was inhibited by either coadministration of chloroquine or transcriptional silencing of the essential autophagy protein BECLIN 1. Enzymatic arginine deprivation is a novel anticancer therapy undergoing clinical trials. This therapy is considered nontoxic and selective, as it allows controlling the growth of malignant tumours deficient in arginine biosynthesis. We propose that arginine deprivation-based combinational treatments that include autophagy inhibitors (e.g., chloroquine) may produce a stronger anticancer effect as a second line therapy for a subset of chemoresistant ovarian cancers. Galyna Shuvayeva, Yaroslav Bobak, Natalia Igumentseva, Rossella Titone, Federica Morani, Oleh Stasyk, and Ciro Isidoro Copyright © 2014 Galyna Shuvayeva et al. All rights reserved. Increased Stem Cell Marker Expressions during the Peri-Implantation Period in the Rat Endometrium: Constructive Role of Exogenous Zinc and/or Progesterone Mon, 26 May 2014 06:38:04 +0000 Background. The aim of this study is to determine the effects of zinc and/or progesterone via the expression of αvβ5 integrins and Vitronectins and embryonic stem cell markers during the peri-implantation period. Methods. Four experimental groups were organized. All subjects were mated with males of the same strain to induce pregnancy; after 5 days, zinc and/or progesterone were administered. Blood levels of zinc and progesterone were determined on the sixth day and endometrial tissues were obtained in order to evaluate the immunohistochemical expression of integrins and embryonic stem cell markers. Results. The αvβ5 integrin and vitronectin expression increased in the zinc group compared with the control group and no difference in the progesterone group and zinc + progesterone group. Expression of Klf-4, Sox-2, and c-Myc was found to be increased in the zinc group compared to controls, while no difference was determined between the progesterone, zinc + progesterone, and control groups. Distinctively, expression of the embryonic stem cell marker Oct-4 was increased in all of the experimental groups. Conclusions. Expression of αvβ5 integrin, vitronectin, and embryonic stem cell markers might be increased by the administration of zinc. Our results suggest that zinc could be useful in the induction of implantation rates. Cagdas Sahin, Ozlem Yilmaz Dilsiz, Sirin Bakti Demiray, Ozgur Yeniel, Mete Ergenoglu, Ebru Demirel Sezer, Gulperi Oktem, Ege Nazan Tavmergen Goker, and Erol Tavmergen Copyright © 2014 Cagdas Sahin et al. All rights reserved. Molecular Profiling and Clinical Outcome of High-Grade Serous Ovarian Cancer Presenting with Low- versus High-Volume Ascites Sun, 25 May 2014 12:40:48 +0000 Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes. Tomer Feigenberg, Blaise Clarke, Carl Virtanen, Anna Plotkin, Michelle Letarte, Barry Rosen, Marcus Q. Bernardini, Alexandra Kollara, Theodore J. Brown, and K. Joan Murphy Copyright © 2014 Tomer Feigenberg et al. All rights reserved. Influence of the Umbilical Cord Insertion Site on the Optimal Individual Birth Weight Achievement Sun, 25 May 2014 05:04:42 +0000 Study Question. To determine whether the umbilical cord insertion site of singleton pregnancies could be linked to the newborn birth weight at term and its individual growth potential achievement. Material and Methods. A cohort study including 528 records of term neonates was performed. Each neonate was assessed for growth adjusted for gestational age according to the infant’s growth potential using the AUDIPOG module. We considered two categories of umbilical cord insertions: central and peripheral. Intrauterine growth restriction was defined as birth weight below the 10th percentile. Statistical analysis was performed using Chi-square, Student’s t test, Wilcoxon test, ANOVA, and logistic regression. Results. We observed a total of 343 centrally inserted cords versus 185 peripheral cords. There were twice as many smokers in the mothers of the peripheral category compared to the centrally inserted ones. More importantly, we demonstrated that only 17/343 (5.0%) of infants with central cord insertion were growth restricted, compared to 37/185 (20.0%) of the infants born with a peripheral insertion. Neonates with centrally inserted cord were significantly heavier. Conclusion. The umbilical cord insertion site of singleton pregnancies is associated with the newborn’s birth weight at term and its individual growth potential achievement. Sophie Brouillet, Anaïs Dufour, Fabien Prot, Jean-Jacques Feige, Véronique Equy, Nadia Alfaidy, Pierre Gillois, and Pascale Hoffmann Copyright © 2014 Sophie Brouillet et al. All rights reserved. Metadherin, p50, and p65 Expression in Epithelial Ovarian Neoplasms: An Immunohistochemical Study Thu, 22 May 2014 06:18:59 +0000 NF-κB signaling promotes cancer progression in a large number of malignancies. Metadherin, a coactivator of the NF-κB transcription complex, was recently identified to regulate different signaling pathways that are closely related to cancer. We assessed the immunohistochemical expression of p50, p65, and metadherin in 30 ovarian carcinomas, 15 borderline ovarian tumours, and 31 benign ovarian cystadenomas. Ovarian carcinomas exhibited significantly higher expression of all 3 markers compared to benign ovarian tumours. Borderline ovarian tumours demonstrated significantly higher expression for all 3 markers compared to benign cystadenomas. Ovarian carcinomas demonstrated significantly higher expression of p50 and metadherin compared to borderline ovarian tumours, whereas no significant difference was noted in p65 expression between ovarian carcinomas and borderline ovarian tumours. There was a strong correlation with the expression levels of p50, p65, and metadherin, whereas no correlation was observed with either grade or stage. Strong p50, p65, and metadherin expression was associated with a high probability to distinguish ovarian carcinomas over borderline and benign ovarian tumours, as well as borderline ovarian tumours over benign ovarian neoplasms. A gradual increase in the expression of these molecules is noted when moving across the spectrum of ovarian carcinogenesis, from borderline ovarian tumours to epithelial carcinomas. Ioanna Giopanou, Vasiliki Bravou, Panagiotis Papanastasopoulos, Ioannis Lilis, Panagiotis Aroukatos, Dionysios Papachristou, Sophia Kounelis, and Helen Papadaki Copyright © 2014 Ioanna Giopanou et al. All rights reserved. Prevalence of Anaemia among Pregnant Women at Booking in the University of Uyo Teaching Hospital, Uyo, Nigeria Mon, 19 May 2014 14:46:48 +0000 Background. Anaemia with an estimated prevalence of 35–75% among pregnant women is a major cause of maternal deaths in Nigeria. Objective. To determine the prevalence of anaemia, associated sociodemographic factors and red cell morphological pattern among pregnant women during booking at the University Teaching Hospital, Uyo. Material and Methods. A cross-sectional analytical study of 400 women at the booking clinic over a 16-week period. The packed cell volume and red cell morphology of each pregnant woman were determined. Their biodata, obstetric and medical histories, and results of other routine investigations were obtained with questionnaires and analyzed with SPSS Package version 17.0. Results. The mean packed cell volume was 31.8% and 54.5% of the women were anaemic. The commonest blood picture was microcytic hypochromia and normocytic hypochromia suggesting iron deficiency anaemia. Anaemia was significantly and independently related to a history of fever in the index pregnancy (; ; 95% –0.7), HIV positive status (; ; 95% –0.6), and low social class (; ; 95% –0.7). Conclusion. Women need to be economically empowered and every pregnant woman should be encouraged to obtain antenatal care, where haematinics supplementation can be given and appropriate investigations and treatment of causes of fever and management of HIV can be instituted. Olujimi A. Olatunbosun, Aniekan M. Abasiattai, Emem A. Bassey, Robert S. James, Godwin Ibanga, and Anyiekere Morgan Copyright © 2014 Olujimi A. Olatunbosun et al. All rights reserved. Women’s Choice of Positions during Labour: Return to the Past or a Modern Way to Give Birth? A Cohort Study in Italy Thu, 15 May 2014 09:34:03 +0000 Background. Childbirth medicalization has reduced the parturient’s opportunity to labour and deliver in a spontaneous position, constricting her to assume the recumbent one. The aim of the study was to compare recumbent and alternative positions in terms of labour process, type of delivery, neonatal wellbeing, and intrapartum fetal head rotation. Methods. We conducted an observational cohort study on women at pregnancy term. Primiparous women with physiological pregnancies and single cephalic fetuses were eligible for the study. We considered data about maternal-general characteristics, labour process, type of delivery, and neonatal wellbeing at birth. Patients were divided into two groups: Group-A if they spent more than 50% of labour in a recumbent position and Group-B when in alternative ones. Results. 225 women were recruited (69 in Group-A and 156 in Group-B). We found significant differences between the groups in terms of labour length, Numeric Rating Scale score and analgesia request rate, type of delivery, need of episiotomy, and fetal occiput rotation. No differences were found in terms of neonatal outcomes. Conclusion. Alternative maternal positioning may positively influence labour process reducing maternal pain, operative vaginal delivery, caesarean section, and episiotomy rate. Women should be encouraged to move and deliver in the most comfortable position. Salvatore Gizzo, Stefania Di Gangi, Marco Noventa, Veronica Bacile, Alessandra Zambon, and Giovanni Battista Nardelli Copyright © 2014 Salvatore Gizzo et al. All rights reserved. Power of Proteomics in Linking Oxidative Stress and Female Infertility Mon, 12 May 2014 12:29:57 +0000 Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions. Sajal Gupta, Jana Ghulmiyyah, Rakesh Sharma, Jacques Halabi, and Ashok Agarwal Copyright © 2014 Sajal Gupta et al. All rights reserved. Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients Thu, 08 May 2014 12:45:11 +0000 Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulation. During EMT epithelial antigens are downregulated; thus, such tumor cells might elude classical epithelial marker-based detection. Several researchers postulated that some CTCs express stem cell-like phenotype; this might lead to chemoresistance and enhanced metastatic potential of such cells. In the present review, we discuss current data on EMT and stem cell markers in CTCs of breast cancer and their clinical significance. Natalia Krawczyk, Franziska Meier-Stiegen, Malgorzata Banys, Hans Neubauer, Eugen Ruckhaeberle, and Tanja Fehm Copyright © 2014 Natalia Krawczyk et al. All rights reserved. Association between Follicular Fluid Leptin and Serum Insulin Levels in Nonoverweight Women with Polycystic Ovary Syndrome Sun, 04 May 2014 14:10:35 +0000 Aims. We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). Materials and Methodology. We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17-β-estradiol (17β-E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). Results. In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. Conclusions. Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance. G. Garruti, R. de Palo, M. T. Rotelli, S. Nocera, I. Totaro, C. Nardelli, M. A. Panzarino, M. Vacca, L. E. Selvaggi, and F. Giorgino Copyright © 2014 G. Garruti et al. All rights reserved. Macrophages and Leydig Cells in Testicular Biopsies of Azoospermic Men Sun, 04 May 2014 13:09:18 +0000 A number of studies have indicated that testicular macrophages play an important role in regulating steroidogenesis of Leydig cells and maintain homeostasis within the testis. The current paper deals with macrophages (CD68 positive cells) and Leydig cells in patients with nonobstructive azoospermia (NOA). Methods employed included histological analysis on semi- and ultrathin sections, immunohistochemistry, morphometry, and hormone analysis in the blood serum. Histological analysis pointed out certain structural changes of macrophages and Leydig cells in NOA group of patients when compared to controls. In the testis interstitium, an increased presence of CD68 positive cells has been noted. Leydig cells in NOA patients displayed a kind of a mosaic picture across the same bioptic sample: both normal and damaged Leydig cells with pronounced vacuolisation and various intensity of expression of testosterone have been observed. Stereological analysis indicated a significant increase in volume density of both CD68 positive and vacuolated Leydig cells and a positive correlation between the volume densities of these cell types. The continuous gonadotropin overstimulation of Leydig cells, together with a negative paracrine action of macrophages, could result in the damage of steroidogenesis and deficit of testosterone in situ. Trpimir Goluža, Alexander Boscanin, Jessica Cvetko, Viviana Kozina, Marin Kosović, Maja Marija Bernat, Miro Kasum, Željko Kaštelan, and Davor Ježek Copyright © 2014 Trpimir Goluža et al. All rights reserved. Epigenetic Control of Autophagy by MicroRNAs in Ovarian Cancer Wed, 30 Apr 2014 13:21:40 +0000 Autophagy is a lysosomal-driven catabolic process that contributes to the preservation of cell homeostasis through the regular elimination of cellular damaged, aged, and redundant molecules and organelles. Autophagy plays dual opposite roles in cancer: on one hand it prevents carcinogenesis; on the other hand it confers an advantage to cancer cells to survive under prohibitive conditions. Autophagy has been implicated in ovarian cancer aggressiveness and in ovarian cancer cell chemoresistance and dormancy. Small noncoding microRNAs (miRNAs) regulate gene expression at posttranscriptional level, thus playing an important role in many aspects of cell pathophysiology, including cancerogenesis and cancer progression. Certain miRNAs have recently emerged as important epigenetic modulators of autophagy in cancer cells. The mRNA of several autophagy-related genes contains, in fact, the target sequence for miRNAs belonging to different families, with either oncosuppressive or oncogenic activities. MiRNA profiling studies have identified some miRNAs aberrantly expressed in ovarian cancer tissues that can impact autophagy. In addition, plasma and stroma cell-derived miRNAs in tumour-bearing patients can regulate the expression of relevant autophagy genes in cancer cells. The present review focuses on the potential implications of miRNAs regulating autophagy in ovarian cancer pathogenesis and progression. Rossella Titone, Federica Morani, Carlo Follo, Chiara Vidoni, Delia Mezzanzanica, and Ciro Isidoro Copyright © 2014 Rossella Titone et al. All rights reserved. New Tools for Embryo Selection: Comprehensive Chromosome Screening by Array Comparative Genomic Hybridization Tue, 29 Apr 2014 08:53:46 +0000 The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH). The study included 1420 CCS cycles for recurrent miscarriage (); repetitive implantation failure (); severe male factor (); previous trisomic pregnancy (); and advanced maternal age (). CCS was performed in cycles with fresh oocytes and embryos (); mixed cycles with fresh and vitrified oocytes (); mixed cycles with fresh and vitrified day-2 embryos (); and mixed cycles with fresh and vitrified day-3 embryos (). Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5 embryo transfer. Consistent implantation (range: 40.5–54.2%) and pregnancy rates per transfer (range: 46.0–62.9%) were obtained for all the indications and independently of the origin of the oocytes or embryos. However, a lower delivery rate per cycle was achieved in women aged over 40 years (18.1%) due to the higher percentage of aneuploid embryos (85.3%) and lower number of cycles with at least one euploid embryo available per transfer (40.3%). We concluded that aneuploidy is one of the major factors which affect embryo implantation. Lorena Rodrigo, Emilia Mateu, Amparo Mercader, Ana Cristina Cobo, Vanessa Peinado, Miguel Milán, Nasser Al-Asmar, Inmaculada Campos-Galindo, Sandra García-Herrero, Pere Mir, Carlos Simón, and Carmen Rubio Copyright © 2014 Lorena Rodrigo et al. All rights reserved. Long-Term Outcome after Laparoscopic Bowel Resections for Deep Infiltrating Endometriosis: A Single-Center Experience after 900 Cases Tue, 29 Apr 2014 07:39:12 +0000 Background. Laparoscopic bowel resections for endometriosis are safe and effective but only short-term follow-up has been evaluated. In the present study long-term outcome in terms of intestinal and urinary function, fertility, chronic pain, and recurrence was assessed. Materials and Methods. From January 2002 to December 2010 nine hundred patients underwent laparoscopic bowel resection for endometriosis, and on 774 (86%) a questionnaire was administered. Patients were divided into 3 groups on the strength of the operation date. Postoperative diarrhea, constipation, rectal bleeding, tenesmus, dyschezia, dysuria, dyspareunia, fertility, and recurrence of disease were assessed. Results. The median follow-up was 54 months (range 1–120). All the evaluated symptoms significantly improved over time, with for dyspareunia, constipation, and pelvic pain and for diarrhea. Nonsignificant improvement was reported for dysuria and rectal bleeding (with and , resp.). Conclusions. The present results confirm that bowel resections for endometriosis are correlated with an acceptable complication rate even at long-term follow-up and that symptoms significantly improve over time, except for rectal bleeding and dysuria, the latter associated with a neurological damage. Giacomo Ruffo, Filippo Scopelliti, Alberto Manzoni, Alberto Sartori, Roberto Rossini, Marcello Ceccaroni, Luca Minelli, Stefano Crippa, Stefano Partelli, and Massimo Falconi Copyright © 2014 Giacomo Ruffo et al. All rights reserved. Distensibility and Strength of the Pelvic Floor Muscles of Women in the Third Trimester of Pregnancy Mon, 28 Apr 2014 14:18:49 +0000 Objective. The objective of this study was to compare the role of the pelvic floor muscles between nulliparous and multiparous women in the third trimester of pregnancy, by analyzing the relationship between electrical activity (surface electromyography—EMG), vaginal palpation (modified Oxford scale), and perineal distensibility (Epi-no). Methods. This was an observational cross-sectional study on a sample of 60 healthy pregnant women with no cervical dilation, single fetus, gestational age between 35 and 40 weeks, and maternal age ranging from 15 to 40 years. The methods used were bidigital palpation (modified Oxford scale, graded 0–5), surface EMG (electrical activity during maximal voluntary contraction), and perineal distensibility (Epi-no device). The Pearson correlation coefficient () was used to analyze the Epi-no values and the surface EMG findings. The Kruskal-Wallis test was used to compare the median values from surface EMG and Epi-no, using the modified Oxford scale scores. Results. Among the 60 patients included in this study, 30 were nulliparous and 30 multiparous. The average maternal age and gestational age were 26.06 (±5.58) and 36.56 (±1.23), respectively. It was observed that nulliparous women had both higher perineal muscle strength ( versus ; ) and higher electrical activity ( μV versus  μV; ), while among the multiparous women, distensibility was higher ( versus ; ). We observed that there was no correlation between perineal distensibility and electrical activity during maximal voluntary contraction (; ). However, we found a positive relationship between vaginal palpation and surface electromyography (), but none between Epi-no values (). Conclusion. The electrical activity and muscle strength of the pelvic floor muscles of the multiparous women were damaged, in relation to the nulliparous women, while the perineal distensibility was lower in the latter group. There was a positive relationship between surface EMG and the modified Oxford scale. Carla Dellabarba Petricelli, Ana Paula Magalhães Resende, Julio Elito Júnior, Edward Araujo Júnior, Sandra Maria Alexandre, Miriam Raquel Diniz Zanetti, and Mary Uchiyama Nakamura Copyright © 2014 Carla Dellabarba Petricelli et al. All rights reserved. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration Mon, 28 Apr 2014 13:51:33 +0000 The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity. Delphine Haouzi, Laurence Bissonnette, Anna Gala, Said Assou, Frida Entezami, Hélène Perrochia, Hervé Dechaud, Jean-Noel Hugues, and Samir Hamamah Copyright © 2014 Delphine Haouzi et al. All rights reserved. Calcium Influx and Male Fertility in the Context of the Sperm Proteome: An Update Sun, 27 Apr 2014 12:25:42 +0000 Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an oocyte. The fertilization aptness of spermatozoa depends on the appropriate and time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the acrosome reaction, where calcium (Ca2+) is extensively involved in almost every step. A literature review showed that several ion channel proteins are likely responsible for regulation of the Ca2+ uptake in spermatozoa. Therefore, manipulation of the functions of channel proteins is closely related to Ca2+ influx, ultimately affecting male fertility. Recently, it has been shown that, together with different physiological stimuli, protein-protein interaction also modifies the Ca2+ influx mechanism in spermatozoa. Modern proteomic analyses have identified several sperm proteins, and, therefore, these findings might provide further insight into understanding the Ca2+ influx, protein functions, and regulation of fertility. The objective of this review was to synthesize the published findings on the Ca2+ influx mechanism in mammalian spermatozoa and its implications for the regulation of male fertility in the context of sperm proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins that regulate the Ca2+ influx signaling by using the information available from the PubMed database following a MedScan Reader (5.0) search. Md Saidur Rahman, Woo-Sung Kwon, and Myung-Geol Pang Copyright © 2014 Md Saidur Rahman et al. All rights reserved. Synchronous and Metachronous Breast Malignancies: A Cross-Sectional Retrospective Study and Review of the Literature Sun, 27 Apr 2014 07:55:57 +0000 Objective. There is increasing interest in patients with metachronous (MBC) and synchronous breast cancer (SBC). The objective of this study was to evaluate the occurrence and outcome of MBCs and SBCs. Methods. A retrospective study on women operated in our department for breast cancer between 2002 and 2005 was carried out. Patients were divided into three groups: women with MBC, SBC, and unilateral breast cancer (UBC). Moreover, we performed a meta-analysis of the English literature about multiple breast cancers between 2000 and 2011 taking into consideration their prevalence and overall survival (OS). Results. We identified 584 breast cancer patients: 16 women (3%) presented SBC and 40 MBC (7%, second cancer after 72-month follow-up IQR 40–145). Although the meta-analysis showed significant OS differences between MBC or SBC and UBC, we did not observe any significant OS difference among the three groups of our population. Anyway, we found a significant worse disease-free survival in MBC than UBC and a significant higher prevalence of radical surgery in MBC and SBC than UBC. Conclusions. Despite the low prevalence of MBC and SBC, the presence of a long time risk of MBC confirms the crucial role of ipsi- and contralateral mammographies in the postoperative follow-up. Ambrogio P. Londero, Sergio Bernardi, Serena Bertozzi, Vito Angione, Giuliana Gentile, Cinzia Dri, Antonio Minucci, Filippo Caponnetto, and Roberto Petri Copyright © 2014 Ambrogio P. Londero et al. All rights reserved. Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow? Wed, 23 Apr 2014 16:30:34 +0000 Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates. Carlo Bastianelli, Manuela Farris, Stefania Rapiti, Roberta Bruno Vecchio, and Giuseppe Benagiano Copyright © 2014 Carlo Bastianelli et al. All rights reserved. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II Wed, 23 Apr 2014 07:01:04 +0000 Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT). With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ), undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells. Masafumi Koshiyama, Noriomi Matsumura, and Ikuo Konishi Copyright © 2014 Masafumi Koshiyama et al. All rights reserved. Maternal Body Mass Index and Risk of Obstetric Anal Sphincter Injury Tue, 15 Apr 2014 14:04:29 +0000 Objective. To estimate the association between maternal obesity and risk of three different degrees of severity of obstetric anal sphincter injury. Methods. The study population consisted of 436,482 primiparous women with singleton term vaginal cephalic births between 1998 and 2011 identified in the Swedish Medical Birth Registry. Women were grouped into six categories of BMI. BMI 18.5–24.9 was set as reference. Primary outcome was third-degree perineal laceration, partial or total, and fourth-degree perineal laceration. Adjustments were made for year of delivery, maternal age, fetal head position at delivery, infant birth weight and instrumental delivery. Results. The overall prevalence of third- or four-degree anal sphincter injury was 6.6% (partial anal sphincter injury 4.6%, total anal sphincter injury 1.2%, unclassified as either partial and total 0.2%, or fourth degree lacerations 0.6%). The risk for a partial, total, or a fourth-degree anal sphincter injury decreased with increasing maternal BMI most pronounced for total anal sphincter injury where the risk among morbidly obese women was half that of normal weight women, OR 0.47 95% CI 0.28–0.78. Conclusion. Obese women had a favourable outcome compared to normal weight women concerning serious pelvic floor damages at birth. Marie Blomberg Copyright © 2014 Marie Blomberg. All rights reserved. Application of MicroRNA in Diagnosis and Treatment of Ovarian Cancer Tue, 15 Apr 2014 12:54:20 +0000 Ovarian cancer has a poor prognosis because early detection is difficult and recurrent ovarian cancer is usually drug-resistant. The morbidity and mortality of ovarian cancer are high worldwide and new methods of diagnosis and therapy are needed. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression that are involved in carcinogenesis, metastasis, and invasion. Thus, miRNAs are likely to be useful as diagnostic and prognostic biomarkers and for cancer therapy. Many miRNAs have altered expression in ovarian cancer compared to normal ovarian tissues and these changes may be useful for diagnosis and treatment. For example, deficiencies of enzymes including Dicer and Drosha that are required for miRNA biogenesis may be adverse prognostic factors; miRNAs such as miR-214 and miR-31, which are involved in drug resistance, and the miR-200 family, which is implicated in metastasis, may serve as biomarkers; and transfection of downregulated miRNAs and inhibition of upregulated miRNAs may be effective for treatment of ovarian cancer. Chemotherapy targeting epigenetic mechanisms associated with miRNAs may also be effective to reverse gene silencing. Kouji Banno, Megumi Yanokura, Miho Iida, Masataka Adachi, Kanako Nakamura, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Iori Kisu, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, and Daisuke Aoki Copyright © 2014 Kouji Banno et al. All rights reserved. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges Mon, 14 Apr 2014 09:55:32 +0000 Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine. Vladislav Volarevic, Sanja Bojic, Jasmin Nurkovic, Ana Volarevic, Biljana Ljujic, Nebojsa Arsenijevic, Majlinda Lako, and Miodrag Stojkovic Copyright © 2014 Vladislav Volarevic et al. All rights reserved. Singleton Pregnancy Outcomes after In Vitro Fertilization with Fresh or Frozen-Thawed Embryo Transfer and Incidence of Placenta Praevia Sun, 13 Apr 2014 00:00:00 +0000 The aim of the study was to compare the single pregnancy and neonate outcome after fresh and frozen-thawed embryo transfer in the in vitro fertilization programme (IVF). The study focused on clinical and laboratory factors affecting the abnormal placentation, especially placenta praevia, in patients conceiving in the IVF programme. The results confirm that neonates born after frozen-thawed embryo transfer had significantly higher mean birth weight than after fresh embryo transfer (ET). Moreover, the birth weight distribution in singletons was found to shift towards “large for gestation” (LGA) after frozen-thawed ET. On the other hand, the pregnancies after fresh ET were characterized by a higher incidence of placenta praevia and 3rd trimester bleeding. Placenta praevia was more common in IVF patients with fresh ET in a stimulated cycle than in patients with ET in a spontaneous cycle. It occurred more frequently in patients with transfer of 2 embryos. From this point of view, single ET and ET in a spontaneous cycle should be encouraged in good prognosis patients in the future with more than two good quality embryos developed. An important issue arose of how the ovarian hormonal stimulation relates to abnormal placentation and if the serum hormone levels interfere with in the IVF treatment results. Sara Korosec, Helena Ban Frangez, Ivan Verdenik, Urska Kladnik, Vanja Kotar, Irma Virant-Klun, and Eda Vrtacnik Bokal Copyright © 2014 Sara Korosec et al. All rights reserved. Evaluation of the Usefulness of the MRI Jelly Method for Diagnosing Complete Cul-de-Sac Obliteration Thu, 10 Apr 2014 14:09:53 +0000 Objective. We conducted a single-center study to evaluate the usefulness of the magnetic resonance (MR) imaging jelly method for diagnosing endometriosis-associated adhesions in the Pouch of Douglas. Methods. Thirty women with menstrual pain, dyspareunia, and chronic pelvic pain were enrolled in the study. All had been scheduled for laparoscopic surgery on the basis of pelvic and/or ultrasonographic (US) evaluation. All underwent MR imaging both with and without application of US jelly to the vagina and rectum. The images were compared and analyzed postsurgically in a random and blinded fashion by a radiology specialist and a radiology fellow. The radiologists’ interpretations of the images were compared to the surgical findings recorded on DVDs. Results. Adhesions in the Pouch of Douglas were found in 21 patients. The sensitivity and specificity of MR imaging without jelly administration were 85.7% and 55.6%, respectively, for the specialist and 81.0% and 55.6%, respectively, for the fellow; with jelly administration, values were 95.2% and 88.9% for the specialist and 90.5% and 66.7% for the fellow. Opacity produced by the jelly increased the sensitivity and specificity for both radiologists. Conclusion. The MRI jelly method is a potentially useful, beneficial, and simple approach for diagnosing Pouch of Douglas adhesions. Iwaho Kikuchi, Ryohei Kuwatsuru, Kana Yamazaki, Jun Kumakiri, Yoichi Aoki, and Satoru Takeda Copyright © 2014 Iwaho Kikuchi et al. All rights reserved. Clinical and Structural Features of Sperm Head Vacuoles in Men Included in the In Vitro Fertilization Programme Wed, 09 Apr 2014 14:13:36 +0000 The human sperm head vacuoles and their role in male infertility are still poorly understood. The aim of this study was to identify the clinical and ultrastructural features of human sperm head vacuoles in men included in the in vitro fertilization programme: men with normal (normozoospermia) and impaired sperm morphology (teratozoospermia). The sperm samples were observed under 6000-time magnification using motile sperm organelle morphology examination (MSOME). The proportion of sperm with head vacuoles was evaluated and related to the outcome of in vitro fertilization. The sperm of men with impaired sperm morphology was characterized by a higher proportion of sperm head vacuoles. The sperm head vacuoles were related to impaired semen quality (sperm concentration, motility, and morphology) but were not influenced by male factors (semen volume, height, age, weight, or body mass index). Moreover, sperm head vacuoles were related to impaired fertilization rate merely after classical in vitro fertilization (IVF), while there was no relation to pregnancy. In a subgroup of men, the sperm was fixed and observed by transmission electron microscopy (TEM). The ultrastructural study revealed that sperm head vacuoles are large nuclear indentations of various sizes and positions, packed with membranous material organized in membrane whorls (MW). Nina Fekonja, Jasna Štrus, Magda Tušek Žnidarič, Katja Knez, Eda Vrtacnik Bokal, Ivan Verdenik, and Irma Virant-Klun Copyright © 2014 Nina Fekonja et al. All rights reserved. Estimating Rate of Insulin Resistance in Patients with Preeclampsia Using HOMA-IR Index and Comparison with Nonpreeclampsia Pregnant Women Wed, 09 Apr 2014 13:27:37 +0000 Women with preeclampsia, independent of obesity and glucose intolerance, exhibit insulin resistance during pregnancy. The purpose of the present study is to determine whether early diagnosis of insulin resistance during pregnancy can predict preeclampsia. Through a case-control study, 675 pregnant women were selected and their first trimester blood was taken. Their fasting blood glucose and insulin were also measured after diagnosis of preeclampsia by 20 weeks of pregnancy. Based on the experiments conducted on 675 women who were 20 weeks past their pregnancy, 375 cases with preeclampsia were selected and assigned to the case group. 35 other pregnant women were put in the control group. Diagnosis criteria for the participants included blood pressure above 140/90 and proteinuria above 300 mg or above +1. Both groups were matched according to age, parity, gestational age, and BMI. Homa-Irand rate of insulin resistance was calculated by HOMA-IR and patients were followed up. Homeostatic model assessments (HOMA-IR) revealed that the average insulin resistance increased during pregnancy among both the case and control groups. There was a significant difference between insulin resistance of these two groups in both first trimester and third trimester and after developing preeclampsia ( < 0.001, = 0.021). Insulin-resistance of the group with preeclampsia was higher in first trimester prior to diagnosis as well as the third trimester after diagnosis compared to natural pregnancy under similar conditions. Measurement of insulin resistance in first trimester may be useful in predicting the risk of preeclampsia. Farideh Rezaei Abhari, Maryam Ghanbari Andarieh, Asadollah Farokhfar, and Soleiman Ahmady Copyright © 2014 Farideh Rezaei Abhari et al. All rights reserved. Evaluation of Two Different Analytical Methods for Circulating Tumor Cell Detection in Peripheral Blood of Patients with Primary Breast Cancer Tue, 08 Apr 2014 09:25:58 +0000 Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT. B. A. S. Jaeger, J. Jueckstock, U. Andergassen, J. Salmen, F. Schochter, V. Fink, M. Alunni-Fabbroni, M. Rezai, Th. Beck, M. W. Beckmann, K. Friese, T. W. P. Friedl, W. Janni, and B. Rack Copyright © 2014 B. A. S. Jaeger et al. All rights reserved. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats Tue, 08 Apr 2014 00:00:00 +0000 Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) () and group 4 (47%) (). There was no difference between group 3 (60%) and group 6 (). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models. Bernhard Kraemer, Christian Wallwiener, Taufiek K. Rajab, Christoph Brochhausen, Markus Wallwiener, and Ralf Rothmund Copyright © 2014 Bernhard Kraemer et al. All rights reserved. High HPV Infection Prevalence in Men from Infertile Couples and Lack of Relationship between Seminal HPV Infection and Sperm Quality Sun, 06 Apr 2014 11:11:53 +0000 Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality. Barbara Golob, Mario Poljak, Ivan Verdenik, Mojca Kolbezen Simoniti, Eda Vrtačnik Bokal, and Branko Zorn Copyright © 2014 Barbara Golob et al. All rights reserved. Proteomes of Animal Oocytes: What Can We Learn for Human Oocytes in the In Vitro Fertilization Programme? Thu, 03 Apr 2014 11:25:25 +0000 Oocytes are crucial cells for mammalian reproduction, yet the molecular principles underlying oocyte development are only partially understood. Therefore, contemporary proteomic approaches have been used increasingly to provide new insights into oocyte quality and maturation in various species such as mouse, pig, and cow. Especially, animal studies have helped in elucidating the molecular status of oocytes during in vitro maturation and other procedures of assisted reproduction. The aim of this review is to summarize the literature on mammalian oocyte proteome and secretome research in the light of natural and assisted reproduction and on lessons to be learned for human oocytes, which have so far remained inaccessible for proteome analysis. Irma Virant-Klun and Jeroen Krijgsveld Copyright © 2014 Irma Virant-Klun and Jeroen Krijgsveld. All rights reserved. Good Preservation of Stromal Cells and No Apoptosis in Human Ovarian Tissue after Vitrification Thu, 03 Apr 2014 07:47:01 +0000 The aim of this study was to develop a vitrification procedure for human ovarian tissue cryopreservation in order to better preserve the ovarian tissue. Large size samples of ovarian tissue retrieved from 15 female-to-male transgender subjects (18–38 years) were vitrified using two solutions (containing propylene glycol, ethylene glycol, and sucrose at different concentrations) in an open system. Light microscopy, transmission electron microscopy, and TUNEL assay were applied to evaluate the efficiency of the vitrification protocol. After vitrification/warming, light microscopy showed oocyte nucleus with slightly thickened chromatin and irregular shape, while granulosa and stromal cells appeared well preserved. Transmission electron microscopy showed oocytes with slightly irregular nuclear shape and finely dispersed chromatin. Clear vacuoles and alterations in cellular organelles were seen in the oocyte cytoplasm. Stromal cells had a moderately dispersed chromatin and homogeneous cytoplasm with slight vacuolization. TUNEL assay revealed the lack of apoptosis induction by vitrification in all ovarian cell types. In conclusion after vitrification/warming the stromal compartment maintained morphological and ultrastructural features similar to fresh tissue, while the oocyte cytoplasm was slightly damaged. Although these data are encouraging, further studies are necessary and essential to optimize vitrification procedure. Raffaella Fabbri, Rossella Vicenti, Maria Macciocca, Gianandrea Pasquinelli, Roberto Paradisi, Cesare Battaglia, Nicola Antonio Martino, and Stefano Venturoli Copyright © 2014 Raffaella Fabbri et al. All rights reserved. Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma Wed, 02 Apr 2014 11:07:32 +0000 The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC. J. Glaser, M. H. D. Neumann, Qi Mei, B. Betz, N. Seier, I. Beyer, T. Fehm, H. Neubauer, D. Niederacher, and M. C. Fleisch Copyright © 2014 J. Glaser et al. All rights reserved. Expression Profiles of Epithelial-Mesenchymal Transition-Associated Proteins in Epithelial Ovarian Carcinoma Tue, 01 Apr 2014 09:04:33 +0000 Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples () by immunohistochemistry. Snail was differentially expressed according to the histologic subtype () and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker. Mi-Kyung Kim, Min A Kim, Haeryoung Kim, Yong-Beom Kim, and Yong-Sang Song Copyright © 2014 Mi-Kyung Kim et al. All rights reserved. Review of Clinical Trials on Effects of Oral Antioxidants on Basic Semen and Other Parameters in Idiopathic Oligoasthenoteratozoospermia Mon, 31 Mar 2014 16:37:53 +0000 Infertility affects 50 to 80 million people worldwide. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT). With common diagnostic methods no cause can be found in approximately 30% of cases of male infertility due to OAT and these are considered idiopathic. Reactive oxygen species (ROS) play an important role in male infertility and are proved to be higher in infertile men; antioxidants could oppose their effect. The aim of this paper was to review the literature on clinical trials in the period from year 2000 to year 2013 studying the effects of various types of antioxidant supplements on basic and other sperm parameters and pregnancy rates in subfertile males with idiopathic OAT. The majority of studies were randomized and placebo controlled and confirmed beneficial effect of antioxidants on at least one of the semen parameters; the biggest effect was determined on sperm motility. In many of these trials combinations of more antioxidants were assessed. The optimal dosages of one or more antioxidants were not defined. We concluded that antioxidants play an important role in protecting semen from ROS and can improve basic sperm parameters in case of idiopathic OAT. Senka Imamovic Kumalic and Bojana Pinter Copyright © 2014 Senka Imamovic Kumalic and Bojana Pinter. All rights reserved. Looking for Celiac Disease in Italian Women with Endometriosis: A Case Control Study Mon, 31 Mar 2014 12:13:13 +0000 In the last years, a potential link between endometriosis and celiac disease has been hypothesized since these disorders share some similarities, specifically concerning a potential role of oxidative stress, inflammation, and immunological dysfunctions. We investigated the prevalence of celiac disease among Italian women with endometriosis with respect to general population. Consecutive women with a laparoscopic and histological confirmed diagnosis of endometriosis were enrolled; female nurses of our institution, without a known history of endometriosis, were enrolled as controls. IgA endomysial and tissue transglutaminase antibodies measurement and serum total IgA dosage were performed in both groups. An upper digestive endoscopy with an intestinal biopsy was performed in case of antibodies positivity. Presence of infertility, miscarriage, coexistence of other autoimmune diseases, and family history of autoimmune diseases was also investigated in all subjects. Celiac disease was diagnosed in 5 of 223 women with endometriosis and in 2 of 246 controls (2.2% versus 0.8%; ). Patients with endometriosis showed a largely higher rate of infertility compared to control group (27.4% versus 2.4%; ). Our results confirm that also in Italian population an increased prevalence of celiac disease among patients with endometriosis is found, although this trend does not reach the statistical significance. Luca Santoro, Sebastiano Campo, Ferruccio D’Onofrio, Antonella Gallo, Marcello Covino, Vincenzo Campo, Guglielmo Palombini, Angelo Santoliquido, Giovanni Gasbarrini, and Massimo Montalto Copyright © 2014 Luca Santoro et al. All rights reserved. First Trimester Biomarkers in the Prediction of Later Pregnancy Complications Sun, 30 Mar 2014 09:45:12 +0000 Adverse obstetric outcomes, such as preeclampsia, preterm birth, gestational diabetes, and fetal growth restriction, are poorly predicted by maternal history and risk factors alone, especially in nulliparae. The ability to predict these outcomes from the first trimester would allow for the early initiation of prophylactic therapies, institution of an appropriate model and location of care, and recruitment of a truly “high risk” population to clinical trials of interventions to prevent or ameliorate these conditions. To this end, development of adequately sensitive and specific predictive tests for these outcomes has become a significant focus of perinatal research. This paper reviews the biomarkers involved in these multiparametric tests and also outlines the performance of these tests and issues regarding their introduction into clinical practice. Stefan C. Kane, Fabricio da Silva Costa, and Shaun Brennecke Copyright © 2014 Stefan C. Kane et al. All rights reserved. Meconium Indicators of Maternal Alcohol Abuse during Pregnancy and Association with Patient Characteristics Sun, 30 Mar 2014 08:09:54 +0000 Aim. Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium. Methods. A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics. Results. We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found. Conclusion. Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established. Tamme W. Goecke, Pascal Burger, Peter A. Fasching, Abdulsallam Bakdash, Anne Engel, Lothar Häberle, Franziska Voigt, Florian Faschingbauer, Eva Raabe, Nicolai Maass, Michael Rothe, Matthias W. Beckmann, Fritz Pragst, and Johannes Kornhuber Copyright © 2014 Tamme W. Goecke et al. All rights reserved. Time-Lapse Dynamics of the Mouse Oocyte Chromatin Organisation during Meiotic Resumption Sun, 30 Mar 2014 07:30:33 +0000 In the mammalian oocyte, distinct patterns of centromeres and pericentromeric heterochromatin localisation correlate with the gamete’s developmental competence. Mouse antral oocytes display two main types of chromatin organisation: SN oocytes, with a ring of Hoechst-positive chromatin surrounding the nucleolus, and NSN oocytes lacking this ring. When matured to MII and fertilised, only SN oocytes develop beyond the 2-cell, and reach full term. To give detailed information on the dynamics of the SN or NSN chromatin during meiosis resumption, we performed a 9 hr time-lapse observation. The main significant differences recorded are: (1) reduction of the nuclear area only in SN oocytes; (2) ~17 min delay of GVBD in NSN oocytes; (3) chromatin condensation, after GVBD, in SN oocytes; (4) formation of 4-5 CHCs in SN oocytes; (5) increase of the perivitelline space, ~57 min later in NSN oocytes; (6) formation of a rosette-like disposition of CHCs, ~84 min later in SN oocytes; (7) appearance of the MI plate ~40 min later in NSN oocytes. Overall, we described a pathway of transition from the GV to the MII stage that is punctuated of discrete recordable events showing their specificity and occurring with different time kinetics in the two types of oocytes. Martina Belli, Giulia Vigone, Valeria Merico, Carlo Alberto Redi, Silvia Garagna, and Maurizio Zuccotti Copyright © 2014 Martina Belli et al. All rights reserved. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma Thu, 27 Mar 2014 13:45:46 +0000 Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH) assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% () higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans. Sharifeh Mehrabi, Edward E. Partridge, William Seffens, Xuebiao Yao, and Felix O. Aikhionbare Copyright © 2014 Sharifeh Mehrabi et al. All rights reserved. BACs-on-Beads Technology: A Reliable Test for Rapid Detection of Aneuploidies and Microdeletions in Prenatal Diagnosis Thu, 27 Mar 2014 11:39:01 +0000 The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF) or chorionic villus (CV) samples based on BACs-on-Beads (BoBs) technology and to compare the results with classical karyotyping by Giemsa banding (G-banding) of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH) was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples. Sandra García-Herrero, Inmaculada Campos-Galindo, José Antonio Martínez-Conejero, Vicente Serra, Inés Olmo, Coral Lara, Carlos Simón, and Carmen Rubio Copyright © 2014 Sandra García-Herrero et al. All rights reserved. Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy? Tue, 25 Mar 2014 11:11:32 +0000 Background. Currently the choice of breast cancer therapy is based on prognostic factors. The proliferation marker Ki-67 is used increasingly to determine the method of therapy. The current study analyses the predictive value of Ki-67 in foreseeing breast cancer patients’ responses to neoadjuvant chemotherapy. Methods. This study includes patients with invasive breast cancer treated between 2008 and 2013. The clinical response was assessed by correlating Ki-67 to histological examination, mammography, and ultrasonography findings. Results. The average Ki-67 value in our patients collectively () is 34.9 ± 24.6%. The average Ki-67 value is the highest with 37.4 ± 24.0% in patients with a pCR. The Ki-67 values do not differ significantly among the 3 groups: pCR versus partial pathological response versus stable disease/progress (). However, Ki-67 values of patients with luminal, Her2 enriched, and basal-like cancers differed significantly from each other. Furthermore, within the group of luminal tumors Ki-67 values of patients with versus without pCR also differed significantly. Conclusion. Our data shows that the Ki-67 value predicts the response to neoadjuvant chemotherapy as a function of the molecular subtype, reflecting the daily routine concerning Ki-67 and its impressing potential and limitation as a predictive marker for neoadjuvant chemotherapy response. Juhasz-Böss Ingolf, Mavrova Russalina, Moga Simona, Radosa Julia, Schmidt Gilda, Rainer M. Bohle, Hasenfus Andrea, Solomayer Erich, and Herr Daniel Copyright © 2014 Juhasz-Böss Ingolf et al. All rights reserved. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review Tue, 25 Mar 2014 08:56:54 +0000 Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles. Salvatore Gizzo, Bruno Ferrari, Marco Noventa, Emanuele Ferrari, Tito Silvio Patrelli, Michele Gangemi, and Giovanni Battista Nardelli Copyright © 2014 Salvatore Gizzo et al. All rights reserved. New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies Mon, 24 Mar 2014 07:57:24 +0000 The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. Tanya Milachich Copyright © 2014 Tanya Milachich. All rights reserved. Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study Sun, 23 Mar 2014 13:04:19 +0000 The aim of this study is to determine if the use of preimplantation genetic screening (PGS) by array comparative genomic hybridization (array CGH) and transfer of a single euploid blastocyst in patients with repeated implantation failure (RIF) can improve clinical results. Three patient groups are compared: 43 couples with RIF for whom embryos were selected by array CGH (group RIF-PGS), 33 couples with the same history for whom array CGH was not performed (group RIF NO PGS), and 45 good prognosis infertile couples with array CGH selected embryos (group NO RIF PGS). A single euploid blastocyst was transferred in groups RIF-PGS and NO RIF PGS. Array CGH was not performed in group RIF NO PGS in which 1-2 blastocysts were transferred. One monoembryonic sac with heartbeat was found in 28 patients of group RIF PGS and 31 patients of group NO RIF PGS showing similar clinical pregnancy and implantation rates (68.3% and 70.5%, resp.). In contrast, an embryonic sac with heartbeat was only detected in 7 (21.2%) patients of group RIF NO PGS. In conclusion, PGS by array CGH with single euploid blastocyst transfer appears to be a successful strategy for patients with multiple failed IVF attempts. Ermanno Greco, Sara Bono, Alessandra Ruberti, Anna Maria Lobascio, Pierfrancesco Greco, Anil Biricik, Letizia Spizzichino, Alessia Greco, Jan Tesarik, Maria Giulia Minasi, and Francesco Fiorentino Copyright © 2014 Ermanno Greco et al. All rights reserved. Cryopreservation of Embryos and Oocytes in Human Assisted Reproduction Sun, 23 Mar 2014 11:47:41 +0000 Both sperm and embryo cryopreservation have become routine procedures in human assisted reproduction and oocyte cryopreservation is being introduced into clinical practice and is getting more and more widely used. Embryo cryopreservation has decreased the number of fresh embryo transfers and maximized the effectiveness of the IVF cycle. The data shows that women who had transfers of fresh and frozen embryos obtained 8% additional births by using their cryopreserved embryos. Oocyte cryopreservation offers more advantages compared to embryo freezing, such as fertility preservation in women at risk of losing fertility due to oncological treatment or chronic disease, egg donation, and postponing childbirth, and eliminates religious and/or other ethical, legal, and moral concerns of embryo freezing. In this review, the basic principles, methodology, and practical experiences as well as safety and other aspects concerning slow cooling and ultrarapid cooling (vitrification) of human embryos and oocytes are summarized. János Konc, Katalin Kanyó, Rita Kriston, Bence Somoskői, and Sándor Cseh Copyright © 2014 János Konc et al. All rights reserved. Guideline Concordant Therapy Prolongs Survival in HER2-Positive Breast Cancer Patients: Results from a Large Population-Based Cohort of a Cancer Registry Thu, 20 Mar 2014 14:16:35 +0000 Even though randomized controlled clinical trials demonstrated improved survival by adjuvant trastuzumab treatment of HER2-positive breast cancer patients, data on its effect in clinical routine are scarce. This study evaluated the use and efficacy of trastuzumab in routine treatment of HER2-positive breast cancer patients. Data from the clinical cancer registry Regensburg (Germany) were analyzed. The present study investigated 6,991 female patients with primary invasive breast cancer. In premenopausal HER2-positive patients a considerable increase of trastuzumab therapy was observed from 58.1% in 2006 to 90.9% in 2011, whereas in postmenopausal patients trastuzumab was rather used on a constant rate of 49.1%. Best overall survival (OS) was found in HER2/steroid hormone receptor-positive patients receiving guideline concordant treatment with trastuzumab plus chemotherapy (CHT) plus antihormone therapy (AHT) with a 7-year OS rate of 96% compared to the non-trastuzumab group with a 7-year OS rate of 92%. In multivariable analysis, HER2-positive patients treated with CHT or AHT who did not get trastuzumab, had a worse 7-year OS (65%, versus 79%, ) than the control groups. This population-based study demonstrated that guideline concordant use of adjuvant trastuzumab improves OS for HER2-positive breast cancer patients treated in routine clinical care. E. C. Inwald, O. Ortmann, F. Zeman, M. Koller, F. Hofstädter, M. Gerstenhauer, and M. Klinkhammer-Schalke Copyright © 2014 E. C. Inwald et al. All rights reserved. Awareness about a Life-Threatening Condition: Ectopic Pregnancy in a Network for Surveillance of Severe Maternal Morbidity in Brazil Wed, 19 Mar 2014 09:28:02 +0000 Objective. To assess occurrence of severe maternal complications associated with ectopic pregnancy (EP). Method. A multicenter cross-sectional study was conducted, with prospective surveillance of potentially life-threatening conditions (PLTC), maternal near miss (MNM), and maternal death (MD). EP complications, patient sociodemographic/obstetric characteristics, and conditions of severity management were assessed, estimating prevalence ratios with respective 95% CI. Factors independently associated with greater severity were identified using multiple regression analysis. Results. Of the 9.555 severe maternal morbidity patients, 312 women (3.3%) had complications after EP: 286 (91.7%) PLTC, 25 (8.0%) MNM, and 1 (0.3%) MD. Severe maternal outcome ratio (SMOR) was 0.3/1000 LB among EP cases and 10.8/1000 LB among other causes. Complicated EP patients faced a higher risk of blood transfusion, laparotomy, and lower risk of ICU admission and prolonged hospitalization than women developing complications resulting from other causes. Substandard care was the most common in more severe maternal morbidity and EP cases (22.7% MNM and MD versus 15% PLTC), although not significant. Conclusion. Increased maternal morbidity due to EP raised awareness about the condition and its impact on female reproductive life. No important risk factors for greater severity were identified. Care providers should develop specific guidelines and interventions to prevent severe maternal morbidity. Edilberto Alves Rocha Filho, Danielly Scaranello Santana, Jose Guilherme Cecatti, Maria Laura Costa, Samira Maerrawe Haddad, Mary Angela Parpinelli, Maria Helena Sousa, Rodrigo Soares Camargo, Rodolfo Carvalho Pacagnella, Fernanda Garanhani Surita, and Joao Luiz Pinto e Silva Copyright © 2014 Edilberto Alves Rocha Filho et al. All rights reserved. Time-to-Delivery after Maternal Transfer to a Tertiary Perinatal Centre Tue, 18 Mar 2014 12:15:14 +0000 Objectives. To determine, in women transferred antenatally for acute admission with high risk pregnancies, the numbers who deliver, the average time from transfer to delivery, and whether the reason for transfer influences the time-to-delivery. Methods. A retrospective analysis of time-to-delivery was performed in a population of women transferred to the Royal Brisbane and Women’s Hospital, QLD. Data were obtained from the hospital obstetric, neonatal, and admission databases. Results. A total of 941 women were transferred antenatally with high risk pregnancies where delivery was deemed potentially imminent. Of these 821 (87%) delivered at RBWH. The remaining 120 women (13%) were discharged prior to delivery and then delivered elsewhere. Of the 821 maternal transfers that delivered, the median time to delivery was 24.4 hrs. There were 43% who delivered within 24 hours of admission and 29% who either delivered after 7 days or delivered elsewhere. Most transfers for fetal abnormality delivered in the first 24 hours while most transfers for antepartum haemorrhage and preterm prelabour membrane rupture delivered beyond 24 hours. Conclusion. There are significant differences in time-to-delivery following transfer depending on the reason for transfer and many infants transferred in utero will not deliver imminently. Fiona H. Hutchinson and Mark W. Davies Copyright © 2014 Fiona H. Hutchinson and Mark W. Davies. All rights reserved. Recent Progress in Cryopreservation of Bovine Oocytes Sun, 16 Mar 2014 06:47:21 +0000 Principle of oocyte cryoinjury is first overviewed and then research history of cryopreservation using bovine oocytes is summarized for the last two decades with a few special references to recent progresses. Various types of cryodevices have been developed to accelerate the cooling rate and applied to the oocytes from large domestic species enriched with cytoplasmic lipid droplets. Two recent approaches include the qualitative improvement of IVM oocytes prior to the vitrification and the short-term recovery culture of vitrified-warmed oocytes prior to the subsequent IVF. Supplementation of L-carnitine to IVM medium of bovine oocytes has been reported to reduce the amount of cytoplasmic lipid droplets and improve the cryotolerance of the oocytes, but it is still controversial whether the positive effect of L-carnitine is reproducible. Incidence of multiple aster formation, a possible cause for low developmental potential of vitrified-warmed bovine oocytes, was inhibited by a short-term culture of the postwarm oocytes in the presence of Rho-associated coiled-coil kinase (ROCK) inhibitor. Use of an antioxidant -tocopherol, instead of the ROCK inhibitor, also supported the revivability of the postwarm bovine oocytes. Further improvements of the vitrification procedure, combined with pre- and postvitrification chemical treatment, would overcome the high sensitivity of bovine oocytes to cryopreservation. In-Sul Hwang and Shinichi Hochi Copyright © 2014 In-Sul Hwang and Shinichi Hochi. All rights reserved. Quantitative Proteomics Analysis of Altered Protein Expression in the Placental Villous Tissue of Early Pregnancy Loss Using Isobaric Tandem Mass Tags Thu, 13 Mar 2014 10:00:08 +0000 Many pregnant women suffer miscarriages during early gestation, but the description of these early pregnancy losses (EPL) can be somewhat confusing because of the complexities of early development. Thus, the identification of proteins with different expression profiles related to early pregnancy loss is essential for understanding the comprehensive pathophysiological mechanism. In this study, we report a gel-free tandem mass tags- (TMT-) labeling based proteomic analysis of five placental villous tissues from patients with early pregnancy loss and five from normal pregnant women. The application of this method resulted in the identification of 3423 proteins and 19647 peptides among the patient group and the matched normal control group. Qualitative and quantitative proteomic analysis revealed 51 proteins to be differentially abundant between the two groups (≥1.2-fold, Student's -test, ). To obtain an overview of the biological functions of the proteins whose expression levels altered significantly in EPL group, gene ontology analysis was performed. We also investigated the twelve proteins with a difference over 1.5-fold using pathways analysis. Our results demonstrate that the gel-free TMT-based proteomic approach allows the quantification of differences in protein expression levels, which is useful for obtaining molecular insights into early pregnancy loss. Xiaobei Ni, Xin Li, Yueshuai Guo, Tao Zhou, Xuejiang Guo, Chun Zhao, Min Lin, Zuomin Zhou, Rong Shen, Xirong Guo, Xiufeng Ling, and Ran Huo Copyright © 2014 Xiaobei Ni et al. All rights reserved. Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture Wed, 12 Mar 2014 12:12:54 +0000 This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks) and long-term culture (up to more than 14 months) in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future. Sabine Conrad, Hossein Azizi, Maryam Hatami, Mikael Kubista, Michael Bonin, Jörg Hennenlotter, Markus Renninger, and Thomas Skutella Copyright © 2014 Sabine Conrad et al. All rights reserved. Genetic Variants in the Genes of the Stress Hormone Signalling Pathway and Depressive Symptoms during and after Pregnancy Wed, 12 Mar 2014 11:42:31 +0000 Purpose. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes of the stress hormone signaling pathway, specifically FKBP5, NR3C1, and CRHR1, are associated with depressive symptoms during and after pregnancy. Methods. The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health including the assessment of depressiveness. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of the pregnancy, visit 2 was shortly after birth, and visit 3 was 6–8 months after birth. Germline DNA was collected from 361 pregnant women. Nine SNPs in the above mentioned genes were genotyped. After construction of haplotypes for each gene, a multifactorial linear mixed model was performed to analyse the depression values over time. Results. EPDS values were within expected ranges and comparable to previously published studies. Neither did the depression scores differ for comparisons among haplotypes at fixed time points nor did the change over time differ among haplotypes for the examined genes. No haplotype showed significant associations with depressive symptoms severity during pregnancy or the postpartum period. Conclusion. The analysed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show an association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women. Michael Schneider, Anne Engel, Peter A. Fasching, Lothar Häberle, Elisabeth B. Binder, Franziska Voigt, Jennifer Grimm, Florian Faschingbauer, Anna Eichler, Ulf Dammer, Dirk Rebhan, Manuela Amann, Eva Raabe, Tamme W. Goecke, Carina Quast, Matthias W. Beckmann, Johannes Kornhuber, Anna Seifert, and Stefanie Burghaus Copyright © 2014 Michael Schneider et al. All rights reserved. Decreasing Quality of the New Generations of Anti-Müllerian Hormone Assays Tue, 11 Mar 2014 08:02:14 +0000 Anti-Müllerian hormone (AMH) measurements are widely used to optimize the stimulation protocols. First generation AMH kits correlated well with ovarian reserve and response to stimulation. In the present study we aimed to asses if the new generation kits share the same accurate correlations. Retrospective data were collected from 8323 blood samples. For comparison we used Immunotech I generation kit (ImI 4035 samples), Beckman Coulter II generation kit RUO (BCII RUO 3449, samples) and Beckman Coulter II generation kit with IVD certificate (BCII IVD 839 samples). We compared average AMH concentrations measured with different kits, as well as correlation between kits. We also compared average AMH concentrations in sera collected on different cycle days and samples of different quality of preservation. AMH serum concentrations differed for each kit, ranging 4.4 ± 4.12 (mean ± SD) for the ImI, 2.68 ± 3.15 for the BCII RUO, and 1.64 ± 2.85 for BCII IVD. The mean differences from an adjusted regression model were −48.7%, −40%, and −69.2%, respectively. In conclusion, the changes of the BC AMH kits are unpredictable; however, the improvement of them is still possible. It would be very dangerous to use elaborated stimulation protocol (based on the Ist generation AMH results) with the results from the IInd generation assays. Krzysztof Lukaszuk, Beata Ludwikowska, Joanna Liss, Michal Kunicki, Miroslaw Sawczak, Aron Lukaszuk, Lukasz Plociennik, Grzegorz Jakiel, Tomasz Wasniewski, Izabela Woclawek-Potocka, and Dorota Bialobrzeska Copyright © 2014 Krzysztof Lukaszuk et al. All rights reserved. High-Throughput Analysis of Ovarian Granulosa Cell Transcriptome Mon, 10 Mar 2014 11:47:55 +0000 The quality of follicular oocytes depends on interactions with surrounding granulosa cells. Development of molecular techniques and methods enables better understanding of processes underlying mammalian reproduction on cellular level. The success in reproductive biology and medicine in different species depends on reliable assessment of oocyte and embryo viability which presently mainly bases on embryo morphology. Although successful pregnancies have been achieved using this approach, its precision still should be improved and completed with other, more objective, and accurate assessment strategies. Global profiling of gene expression in follicular cumulus cells using microarrays is continuously leading to the establishment of new biomarkers which can be used to select oocytes with highest developmental potential. Even more potential applications and greater precision could be achieved using next generation sequencing (NGS) of granulosa and cumulus cell RNA (RNA-seq). However, due to the high cost, this method is not used as frequently as microarrays at the moment. In any case, high-throughput technologies offer the possibilities and advantages in ovarian somatic cell analysis on scale that has not been noted so far. The aim of this work is to present current directions and examples of global molecular profiling of granulosa cells and underline its impact on reproductive biology and medicine. Ewa Chronowska Copyright © 2014 Ewa Chronowska. All rights reserved. Cumulative Delivery Rate after Providing Full Reimbursement In Vitro Fertilization Programme: A 6-Years Survey Sun, 09 Mar 2014 06:57:29 +0000 Since 1983, Slovenia has been offering well-established, successful, and fully reimbursed IVF programme to infertile couples. On the grounds of data gathered at the Slovenian IVF units we aimed to determine whether the fully accessible IVF treatment system can provide notable success considering cumulative delivery rate (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of 395 couples who for the first time attended the IVF programme in year 2006 and were followed until year 2012. We calculated the actual and the optimistic cDR. In women aged <38 years the actual cDR was 54% and optimistic DR was 83%, respectively. In women aged ≥38 years the actual cDR was 24 % and optimistic cDR was 27%. These results enable us to report that prospects of the treatment for the women aged <38 years, if they undergo all 6 available IVF cycles, are very positive and quite comparable to the chances of spontaneous conception. Even in older patients it is beneficial to repeat the IVF procedures. Therefore we consider the existing infertility treatment system in Slovenia as an example of good medical practice with high level of beneficence offered to the patients. Urban Vrtacnik, Eda Vrtacnik Bokal, and Rok Devjak Copyright © 2014 Urban Vrtacnik et al. All rights reserved. Quantitative Elastography for Cervical Stiffness Assessment during Pregnancy Wed, 05 Mar 2014 16:42:40 +0000 Aim. Feasibility and reliability of tissue Doppler imaging-(TDI-) based elastography for cervical quantitative stiffness assessment during all three trimesters of pregnancy were evaluated. Materials and Methods. Prospective case-control study including seventy-four patients collected between the 12th and 42nd weeks of gestation. The tissue strain (TS) was measured by two independent operators as natural strain. Intra- and interoperator intraclass correlation coefficient (ICC) agreements were evaluated. Results. TS measurement was always feasible and exhibited a high performance in terms of reliability (intraoperator ICC-agreement = 0.93; interoperator ICC agreement = 0.89 and 0.93 for a single measurement and for the average of two measurements, resp.). Cervical TS showed also a significant correlation with gestational age, cervical length, and parity. Conclusions. TS measurement during pregnancy demonstrated high feasibility and reliability. Furthermore, TS significantly correlated with gestational age, cervical length, and parity. A. Fruscalzo, A. P. Londero, C. Fröhlich, U. Möllmann, and R. Schmitz Copyright © 2014 A. Fruscalzo et al. All rights reserved. Polymorphisms in the RANK/RANKL Genes and Their Effect on Bone Specific Prognosis in Breast Cancer Patients Wed, 05 Mar 2014 13:20:42 +0000 The receptor activator of NF-B (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis-free survival (BMFS), disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health. Alexander Hein, Christian M. Bayer, Michael G. Schrauder, Lothar Häberle, Katharina Heusinger, Reiner Strick, Matthias Ruebner, Michael P. Lux, Stefan P. Renner, Rüdiger Schulz-Wendtland, Arif B. Ekici, Arndt Hartmann, Matthias W. Beckmann, and Peter A. Fasching Copyright © 2014 Alexander Hein et al. All rights reserved. Superoxide Dismutase: A Predicting Factor for Boar Semen Characteristics for Short-Term Preservation Wed, 05 Mar 2014 13:08:23 +0000 Superoxide dismutase (SOD), total antioxidant capacity (TAC), and thiobarbituric acid reactive substances (TBARS) in seminal plasma were evaluated on the basis of receiver operating characteristics (ROC) analysis as predictors for distinguishing satisfactory from unsatisfactory boar semen samples after storage. SOD on day 0 correlated significantly with progressive motility (; ) and viability (; ) after storage; TBARS correlated only with motility (; ). Semen samples that, after 3 days of storage, fulfilled all criteria for semen characteristics (viability > 85%, motility > 70%, progressive motility > 25%, and normal morphology > 50%) had significantly lower SOD levels on the day 0 than those with at least one criterion not fulfilled () following storage. SOD levels of less than 1.05 U/mL predicted with 87.5% accuracy that fresh semen will suit the requirements for satisfactory semen characteristics after storage, while semen with SOD levels higher than 1.05 U/mL will not fulfill with 100% accuracy at least one semen characteristic after storage. These results support the proposal that SOD in fresh boar semen can be used as a predictor of semen quality after storage. Maja Zakošek Pipan, Janko Mrkun, Marjan Kosec, Alenka Nemec Svete, and Petra Zrimšek Copyright © 2014 Maja Zakošek Pipan et al. All rights reserved. Expression of Mesenchymal Stem Cells-Related Genes and Plasticity of Aspirated Follicular Cells Obtained from Infertile Women Mon, 03 Mar 2014 09:32:27 +0000 After removal of oocytes for in vitro fertilization, follicular aspirates which are rich in somatic follicular cells are discarded in daily medical practice. However, there is some evidence that less differentiated cells with stem cell characteristics are present among aspirated follicular cells (AFCs). The aim of this study was to culture AFCs in vitro and to analyze their gene expression profile. Using the RT2 Profiler PCR array, we investigated the expression profile of 84 genes related to stemness, mesenchymal stem cells (MCSs), and cell differentiation in AFCs enriched by hypoosmotic protocol from follicular aspirates of infertile women involved in assisted reproduction programme in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and fibroblasts. Altogether the expression of 57 genes was detected in AFCs: 16 genes (OCT4, CD49f, CD106, CD146, CD45, CD54, IL10, IL1B, TNF, VEGF, VWF, HDAC1, MITF, RUNX2, PPARG, and PCAF) were upregulated and 20 genes (FGF2, CASP3, CD105, CD13, CD340, CD73, CD90, KDR, PDGFRB, BDNF, COL1A1, IL6, MMP2, NES, NUDT6, BMP6, SMURF2, BMP4, GDF5, and JAG1) were downregulated in AFCs when compared with BM-MSCs. The genes which were upregulated in AFCs were mostly related to MSCs and connected with ovarian function, and differed from those in fibroblasts. The cultured AFCs with predominating granulosa cells were successfully in vitro differentiated into adipogenic-, osteogenic-, and pancreatic-like cells. The upregulation of some MSC-specific genes and in vitro differentiation into other types of cells indicated a subpopulation of AFCs with specific stemness, which was not similar to those of BM-MSCs or fibroblasts. Edo Dzafic, Martin Stimpfel, Srdjan Novakovic, Petra Cerkovnik, and Irma Virant-Klun Copyright © 2014 Edo Dzafic et al. All rights reserved. Fetus Sound Stimulation: Cilia Memristor Effect of Signal Transduction Wed, 26 Feb 2014 07:14:54 +0000 Background. This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. Methods. PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. Results. Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the “memristor” property. Conclusion. Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction. Svetlana Jankovic-Raznatovic, Svetlana Dragojevic-Dikic, Snezana Rakic, Branka Nikolic, Snezana Plesinac, Lidija Tasic, Zivko Perisic, Mirjana Sovilj, Tatjana Adamovic, and Djuro Koruga Copyright © 2014 Svetlana Jankovic-Raznatovic et al. All rights reserved. Does Loop Electrosurgical Excision Procedure of the Uterine Cervix Affect Anti-Müllerian Hormone Levels? Sun, 23 Feb 2014 10:00:16 +0000 Background. A delayed time to pregnancy was recently reported for women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN) grade 2 or 3. The objective of the current study was to determine if treatment of CIN with LEEP is associated with decreased levels of anti-Müllerian hormone (AMH), a marker of ovarian reserve. Methods. AMH levels were measured in 18 women treated with LEEP and 18 age-matched controls, who had colposcopy only and did not require LEEP. Cases and controls had their blood drawn at study entry time zero and again 6 months later. Results. The mean AMH level decreased significantly from baseline to follow-up; however, no significant differences were observed when stratifying by LEEP status, suggesting that both groups experienced a similar decrease in AMH levels during the follow-up period. Although women treated with LEEP had lower overall AMH levels than controls at both baseline and follow-up, these differences were not statistically significant. Conclusion. Overall, the delayed time to pregnancy observed in women treated with LEEP is likely not due to a LEEP-associated decrease in ovarian reserve as measured by AMH; thus, other mechanism are responsible for the delayed time to pregnancy associated with LEEP. Martha M. Sklavos, Cassandra N. Spracklen, Audrey F. Saftlas, and Ligia A. Pinto Copyright © 2014 Martha M. Sklavos et al. All rights reserved. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma Wed, 19 Feb 2014 13:30:30 +0000 Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. David L. Wachter, Arndt Hartmann, Matthias W. Beckmann, Peter A. Fasching, Alexander Hein, Christian M. Bayer, and Abbas Agaimy Copyright © 2014 David L. Wachter et al. All rights reserved. Whole Ovine Ovaries as a Model for Human: Perfusion with Cryoprotectants In Vivo and In Vitro Wed, 19 Feb 2014 13:08:52 +0000 These experiments were performed to test the perfusion of ovine as a model for human ovaries by cryoprotectants in vivo at high temperature when the permeability of capillaries is high and when blood is insensibly replaced by the solution of cryoprotectants. By our hypothetical supposition, ovaries could be saturated by cryoprotectants before their surgical removal. The objective was to examine the effectiveness of perfusion of ovine ovaries with vascular pedicle in vivo and in vitro. Arteria ovarica was cannuled and ovaries were perfused by Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink in vivo and in vitro. In the first and second cycle of experiments, ovaries ( and ) were perfused in vivo and in vitro, respectively, during 60 min with the rate of perfusion 50 mL/h (0.8 mL/min). It was established with in vivo perfusion that only about 10% of ovarian tissues were perfused due to an appearance of multiple anastomoses when the perfusion medium goes from arteria ovarica to arteria uterina without inflow into the ovaries. It was concluded that in vitro perfusion of ovine intact ovaries with vascular pedicle by freezing medium is more effective than this manipulation performed in vivo. Vladimir Isachenko, Gohar Rahimi, Maria Dattena, Peter Mallmann, Saltanat Baikoshkarova, Elisabeth Kellerwessel, Marat Otarbaev, Tamara Shalakhmetova, and Evgenia Isachenko Copyright © 2014 Vladimir Isachenko et al. All rights reserved. Maternal OGTT Glucose Levels at 26–30 Gestational Weeks with Offspring Growth and Development in Early Infancy Thu, 13 Feb 2014 12:24:35 +0000 Aims. We aim to evaluate the association of maternal gestational oral glucose tolerance test (OGTT) glucose concentrations with anthropometry in the offspring from birth to 12 months in Tianjin, China. Methods. A total of 27,157 pregnant women underwent OGTT during 26–30 weeks gestation, and their children had body weight/length measured from birth to 12 months old. Results. Maternal OGTT glucose concentrations at 26–30 gestational weeks were positively associated with Z-scores for birth length-for-gestational age and birth weight-for-length. Compared with infants born to mothers with normal glucose tolerance, infants born to mothers with gestational diabetes mellitus (impaired glucose tolerance/new diabetes) had higher mean values of Z-scores for birth length-for-gestational age (0.07/0.23; normal group −0.08) and birth weight-for-length (0.27/0.57; normal group −0.001), smaller changes in mean values of Z-scores for length-for-age (0.75/0.62; normal group 0.94) and weight-for-length (0.18/−0.17; normal group 0.37) from birth to month 3, and bigger changes in mean values in Z-scores for weight-for-length (0.07/0.12; normal group 0.02) from month 9 to 12. Conclusions. Abnormal maternal glucose tolerance during pregnancy was associated with higher birth weight and birth length, less weight and length gain in the first 3 months of life, and more weight gain in the months 9–12 of life. Gongshu Liu, Nan Li, Shurong Sun, Jing Wen, Fengjun Lyu, Wen Gao, Lili Li, Fang Chen, Andrea A. Baccarelli, Lifang Hou, and Gang Hu Copyright © 2014 Gongshu Liu et al. All rights reserved. Effect of Hyaluronan on Developmental Competence and Quality of Oocytes and Obtained Blastocysts from In Vitro Maturation of Bovine Oocytes Thu, 13 Feb 2014 00:00:00 +0000 The objective of the present study was to evaluate the effect of hyaluronan (HA) during IVM on meiotic maturation, embryonic development, and the quality of oocytes, granulosa cells (GC), and obtained blastocysts. COCs were matured in vitro in control medium and medium with additional 0.035% or 0.07% of exogenous HA. The meiotic maturity did not differ between the analysed groups. The best rate and the highest quality of obtained blastocysts were observed when 0.07% HA was used. A highly significant difference () was noted in the mean number of apoptotic nuclei per blastocyst and in the DCI between the 0.07% HA and the control blastocysts (). Our results suggest that addition of 0.035% HA and 0.07% HA to oocyte maturation media does not affect oocyte nuclear maturation and DNA fragmentation. However, the addition of 0.07% HA during IVM decreases the level of blastocysts DNA fragmentation. Finally, our results suggest that it may be risky to increase the HA concentration during IVM above 0.07% as we found significantly higher Bax mRNA expression levels in GC cultured with 0.07% HA. The final concentration of HA being supplemented to oocyte maturation media is critical for the success of the IVP procedure. Jolanta Opiela, Joanna Romanek, Daniel Lipiński, and Zdzisław Smorąg Copyright © 2014 Jolanta Opiela et al. All rights reserved. Evaluation of Granulocyte Colony-Stimulating Factor Effects on Treatment-Resistant Thin Endometrium in Women Undergoing In Vitro Fertilization Wed, 12 Feb 2014 10:02:06 +0000 The aim of the study was to assess the granulocyte colony-stimulating factor (G-CSF) effects on unresponsive thin (<7 mm) endometrium in women undergoing in vitro fertilization (IVF). We included thirty-seven subjects who had thin unresponsive endometrium on the day of triggering ovulation. These patients also failed to achieve an adequate endometrial thickness in at least one of their previous IVF cycles. In all the subjects at the time of infusion of G-CSF, endometrial thickness was 6,74 ± 1,75 mm, and, after infusion, it increased significantly to 8,42 ± 1,73 mm. When we divided the group into two subgroups according to whether the examined women conceived, we showed that the endometrium expanded significantly from 6,86 ± 1,65 to 8,80 ± 1,14 mm in the first group (who conceived) and from 6,71 ± 1,80 to 8,33 ± 1,85 mm in the second, respectively. There were no significant differences between the two subgroups in respect to the endometrial thickness both before and after G-CSF infusion. The clinical pregnancy rate was 18,9%. We concluded that the infusion of G-CSF leads to the improvement of endometrium thickness after 72 hours. Michał Kunicki, Krzysztof Łukaszuk, Izabela Woclawek-Potocka, Joanna Liss, Patrycja Kulwikowska, and Joanna Szczyptańska Copyright © 2014 Michał Kunicki et al. All rights reserved. Fluid Consumption by Mexican Women during Pregnancy and First Semester of Lactation Sun, 02 Feb 2014 09:49:40 +0000 The objective of this study was to describe daily fluid consumption in a sample of pregnant or lactating adult women. Women between 18 and 45 years of age, residents of Mexico City, stratified by socioeconomic status were asked to register their total fluid intake during 7 consecutive days. A total of 153 pregnant and 155 lactating women were recruited. On average, they drank 2.62 L/day and 2.75 L/day, respectively. Forty-one percent of pregnant women drank less than the recommended 2.3 L fluids/day, and 54% of women drank less than the recommended intake of 2.7 L/day during the first semester of lactation. Plain water contributed to 33% of total fluid intake, and sugar-sweetened beverages (SSB) contributed to 38% of total fluid intake. Up to 50% of pregnant and lactating women drank more than 1 L/day of SSB, which contributed to 632 kcal/day (27.5% of recommended dietary intake) and to 700 kcal/day (28% of recommended dietary intake), respectively. The high rates of overweight and obesity found in Mexican population, particularly among women, should alert us to the consumption of SSB during pregnancy and lactation, as excessive intake of these beverages may increase the risks of obesity, diabetes mellitus, and other chronic disorders. Homero Martinez Copyright © 2014 Homero Martinez. All rights reserved. A Comparison of Capillary and Venous Blood Haematocrits of Pregnant Women in Nigeria: The Impact on Diagnosis and Prevalence of Anaemia in Pregnancy Tue, 28 Jan 2014 09:22:38 +0000 Background. Volume of red cells in capillary blood varies from that of venous blood. The magnitude of this variation as well as its impact on the diagnosis of anaemia in pregnancy needs to be studied. This study demonstrates the disparity between capillary and venous PCV in pregnancy. Objectives. To determine whether capillary blood PCV (cPCV) differed from venous blood PCV (vPCV) of normal pregnant women in Enugu, Nigeria, and its effect on diagnosis and prevalence of anaemia. Methods. PCV was estimated using pairs of venous and capillary blood samples from 200 consecutive pregnant women at the Antenatal Clinic of University of Nigeria Teaching Hospital, Enugu, Nigeria. Results. Participants’ cPCV %, was significantly lower than their vPCV %, (, ). However, women’s cPCV had strong positive correlation with their vPCV (, ). The prevalence of anaemia among participants using capillary and venous blood was 33.5% (67/200) and 28.0% (56/200), respectively ( (CI 95%: 0.85, 1.98),  ). Conclusions. Capillary blood PCV was lower than vPCV among pregnant women in Enugu, Nigeria. Nevertheless, the prevalence of anaemia derived from cPCV did not differ significantly from that of vPCV. Cyril Chukwudi Dim, Emmanuel Onyebuchi Ugwu, Ugochukwu Bond Anyaehie, and Kingsley Chukwu Obioha Copyright © 2014 Cyril Chukwudi Dim et al. All rights reserved. Hormonal Contraceptive Use and the Prevalence of Endometriotic Lesions at Different Regions within the Peritoneal Cavity Mon, 20 Jan 2014 11:57:16 +0000 Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial. The purpose of this study was to determine whether HC use affected the prevalence of endometriotic lesions differently based on lesion location. Data was retrospectively collected from 161 patients presenting to the Berne University Women’s Hospital between 2008 and 2012 for laparoscopic investigation. Women with histologically proven endometriosis were included in the study and patients were grouped according to lesion location and HC use. The results of the study indicate that HC users are significantly less likely to have endometriotic lesions on the ovaries, although in contrast, no difference was observed in the incidence of lesions in the rectovaginal septum (RVS) or peritoneal region. In addition, women using HC who were diagnosed with endometriotic lesions on the peritoneum were significantly younger than women with lesions in other locations. In conclusion, women with endometriosis who are currently using HC are less likely to have ovarian endometriotic lesions than in alternate locations. Brett D. McKinnon, Dominic Bertschi, Juilette Wanner, Nick A. Bersinger, and Michael D. Mueller Copyright © 2014 Brett D. McKinnon et al. All rights reserved. Biochemical Markers of Spontaneous Preterm Birth in Asymptomatic Women Sun, 19 Jan 2014 00:00:00 +0000 Preterm birth is a delivery that occurs at less than 37 completed weeks of gestation and it is associated with perinatal morbidity and mortality. Spontaneous preterm birth accounts for up to 75% of all preterm births. A number of maternal or fetal characteristics have been associated with preterm birth, but the use of individual or group biochemical markers have advanced some of the understanding on the mechanisms leading to spontaneous preterm birth. This paper provides a summary on the current literature on the use of biochemical markers in predicting spontaneous preterm birth in asymptomatic women. Evidence from the literature suggests fetal fibronectin, cervical interleukin-6, and -fetoprotein as promising biochemical markers in predicting spontaneous preterm birth in asymptomatic women. The role of gene-gene and gene-environment interactions, as well as epigenetics, has the potential to further elucidate and improve understanding of the underlying mechanisms or pathways of spontaneous preterm birth. Refinement in study design and methodology is needed in future research for the development and validation of individual or group biochemical marker(s) for use independently or in conjunction with other potential risk factors such as genetic variants and environmental and behavioral factors in predicting spontaneous preterm birth across diverse populations. Ronna L. Chan Copyright © 2014 Ronna L. Chan. All rights reserved. The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism Sun, 12 Jan 2014 13:22:23 +0000 Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid. Shuang Liang, Yuanpeng Zhou, Huijun Wang, Yanyan Qian, Duan Ma, Weidong Tian, Vishwani Persaud-Sharma, Chen Yu, Yunyun Ren, Shufeng Zhou, and Xiaotian Li Copyright © 2014 Shuang Liang et al. All rights reserved. Mannose-Binding Lectin Codon 54 Gene Polymorphism and Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis Mon, 06 Jan 2014 09:03:07 +0000 Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10–11.15; for heterogeneity ; %) and 12.68 (95% CI 3.74–42.92; for heterogeneity , %), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29–5.12; for heterogeneity ; %). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women’s innate immunity in response to Candida. Bojan Nedovic, Brunella Posteraro, Emanuele Leoncini, Alberto Ruggeri, Rosarita Amore, Maurizio Sanguinetti, Walter Ricciardi, and Stefania Boccia Copyright © 2014 Bojan Nedovic et al. All rights reserved. Comparative Assessment of Lymph Node Micrometastasis in Cervical, Endometrial and Vulvar Cancer: Insights on the Real Time qRT-PCR Approach versus Immunohistochemistry, Employing Dual Molecular Markers Thu, 02 Jan 2014 11:19:06 +0000 To address the value of qRT-PCR and IHC in accurately detecting lymph node micrometastasis in gynecological cancer, we performed a systematic approach, using a set of dual molecular tumor-specific markers such as cytokeratin 19 (CK19) and carbonic anhydrase 9 (CA9), in a series of 46 patients (19 with cervical cancer, 18 with endometrial cancer, and 9 with vulvar cancer). A total of 1281 lymph nodes were analyzed and 28 were found positive by histopathology. Following this documentation, 82 lymph nodes, 11 positive and 71 negative, were randomly selected and further analyzed both by IHC and qRT-PCR for CK19 and CA9 expression. All 11 (100%) expressed CK19 by IHC, while only 6 (54.5%) expressed CA9. On the contrary, all the histologically negative for micrometastases lymph nodes were also negative by IHC analysis for both markers. The comparative diagnostic efficacy of the two markers using qRT-PCR, however, disclosed that the analysis of the same aliquots of the 82 lymph nodes led to 100% specificity for the CK19 biomarker, while, in contrast, CA9 failed to recapitulate a similar pattern. These data suggest that qRT-PCR exhibits a better diagnostic accuracy compared to IHC, while CK19 displays a consistent pattern of detection compared to CA9. Kalliopi I. Pappa, Alexandros Rodolakis, Ioanna Christodoulou, Maria Gazouli, Sofia Markaki, Aris Antsaklis, and Nicholas P. Anagnou Copyright © 2014 Kalliopi I. Pappa et al. All rights reserved. Effect of Paracetamol, Dexketoprofen Trometamol, Lidocaine Spray, and Paracervical Block Application for Pain Relief during Suction Termination of First-Trimester Pregnancy Tue, 24 Dec 2013 09:12:35 +0000 The aim of the study was to investigate the analgesic efficacy of preoperative oral dexketoprofen trometamol, intravenous paracetamol, lidocaine spray, and paracervical block with ultracaine on curettage procedure. A total of 111 subjects with the request of pregnancy termination between 5 and 7 weeks of gestation were included in the study. The first group (control group) consisted of 20 participants without medication. The second group consisted of 25 participants receiving 2 puffs of lidocaine sprays on cervical mucosa. The third group consisted of 20 participants receiving oral 25 mg dexketoprofen trometamol. The fourth group consisted of 23 participants receiving 1000 mg intravenous paracetamol and the fifth group consisted of 23 participants receiving paracervical block with ultracaine. Paracervical block reduced pain score significantly in both intraoperative and postoperative periods. All analgesic procedures were significantly effective for reducing pain in postoperative period. Paracervical block may be the best method for reducing pain scores in intraoperative and postoperative periods during curettage procedure. All analgesic procedures such as lidocaine, paracetamol, ultracaine, and paracervical block with ultracaine can be used for reducing pain score in postoperative period. This trial is registered with NCT01947205. Gökhan Açmaz, Hüseyin Aksoy, Nil Özoğlu, Ülkü Aksoy, and Evrim Albayrak Copyright © 2013 Gökhan Açmaz et al. All rights reserved. Prognostic Significance of Immunohistochemical Phenotypes in Patients Treated for High-Grade Cervical Intraepithelial Neoplasia Wed, 18 Dec 2013 14:49:28 +0000 Strong evidence exists that the host’s immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (). These data reinforce the evidence of the relevance of the host’s immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates. Massimo Origoni, Marta Parma, Giacomo Dell'Antonio, Chiara Gelardi, Chiara Stefani, Stefano Salvatore, and Massimo Candiani Copyright © 2013 Massimo Origoni et al. All rights reserved. Survey of the Situation of Infertile Women Seeking In Vitro Fertilization Treatment in China Tue, 03 Dec 2013 08:43:50 +0000 Background. In previous studies, people’s knowledge of reproductive health and infertile women’s psychological states was surveyed in several countries. However, there has been limited information concerning the psychological states of infertile women seeking treatment and the outcomes of in vitro fertilization (IVF) in China. Methods. Infertile women were asked to complete short questionnaires on the day that their oocytes were retrieved; these questionnaires covered the durations of their infertility, levels of education, sources of pressure, and psychological states. Data concerning IVF outcomes were provided by embryologists and clinicians. The correlations between the duration of infertility and educational level, psychological state and education level, and psychological state and outcome of IVF were analyzed in the cohort study. Results. The duration of infertility in more than half of the females was longer than 5 years. Compared with less-educated women, women with higher levels of education sought treatment earlier and their rates of depressive symptoms were lower. There is an association between negative emotions and outcome of IVF. Conclusions. The survey of the situations of infertile women seeking IVF treatment in China indicates the importance of popularizing knowledge concerning reproductive health. Improving medical conditions, reducing the costs of treatment, and developing social culture will aid in relieving the stress of infertile women and improving assisted reproductive treatment. Xuan Jin, Gongxian Wang, Sisun Liu, Jing Zhang, Fang Zeng, Yun Qiu, and Xiaojin Huang Copyright © 2013 Xuan Jin et al. All rights reserved. Risks for Gestational Diabetes Mellitus and Pregnancy-Induced Hypertension Are Increased in Polycystic Ovary Syndrome Mon, 25 Nov 2013 09:08:06 +0000 Objectives. To evaluate pregnancy outcomes and its determinants in women with polycystic ovary syndrome (PCOS). Methods. Two-hundred and twenty pregnant PCOS and 594 healthy women were followed from early pregnancy. Incidences of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm birth, twinning, and fetal growth restriction (FGR) were determined. Results. The incidence of GDM was notably higher among all PCOS combined (54.9%; OR: 2.9, 95% CI: 2.0–4.1) and PCOS subgroups, whether they conceived spontaneously (51.5%; OR: 3.3, 95% CI: 2.0–5.4), or via IVF-ET or ovarian stimulation, compared with controls (14.3%; ). The incidence of PIH was also higher among all PCOS (10.4%; OR: 2.2, 95% CI: 1.1–4.4) and the subgroup conceiving spontaneously (11.8%; OR: 2.6, 95% CI: 1.1–6.2; ) but not for those conceiving with IVF-ET (9.1%) or ovarian stimulation (9.4%). Lean women with PCOS (BMI kg/m2) had higher incidences of GDM (51.1% versus 14.5%; OR: 5.6, 95% CI: 3.4–9.0) and PIH (8.9% versus 3.2%; OR: 3.0, 95% CI: 1.3–7.1) than lean controls. PCOS woemn with normal glucose tolerance had higher risk for PIH than their comparable control group (OR: 4.0, 95% CI: 1.3–11.7). Conclusion. This study suggested that PCOS is an independent risk factor for the development of GDM and PIH. This trial is registered with ChiCTR-RCC-11001824. Yunhui Wang, Xiaomiao Zhao, Huidan Zhao, Hong Ding, Jianping Tan, Jingte Chen, Rui Zhang, Ricardo Azziz, and Dongzi Yang Copyright © 2013 Yunhui Wang et al. All rights reserved. Changes in Maternal Serum Transforming Growth Factor Beta-1 during Pregnancy: A Cross-Sectional Study Mon, 18 Nov 2013 17:29:37 +0000 Changes in circulating levels of maternal serum transforming growth factor beta-1 (TGF-β1), collected from 98 women (AGA) at different gestational ages (10–38 weeks) were measured and comparisons were made between levels in pregnant and nonpregnant controls and also between 10 women with small-for-gestational age (SGA) and 7 with appropriate-for-gestational age (AGA) fetuses. Maternal serum TGF-β1 levels at all stages of pregnancy were higher than those in normal healthy nonpregnant adults. The mean TGF-β1 levels in SGA pregnancies at 34-week gestation (32.5 + 3.2 ng/mL) were significantly less than those in AGA pregnancies (39.2 + 9.8 ng/mL) while at 38-week gestation, the levels were similar in the two groups (36.04 + 4.3 versus 36.7 + 7.0 ng/mL). This differential change in TGF-β1 levels is probably an important modulating factor in the aetiopathogenesis of abnormal intrauterine fetal growth. Mandeep Singh, Ngozi C. Orazulike, Jill Ashmore, and Justin C. Konje Copyright © 2013 Mandeep Singh et al. All rights reserved. An Influence of Immunomodulation on Th1 and Th2 Immune Response in Endometriosis in an Animal Model Tue, 05 Nov 2013 15:59:49 +0000 Aim. To assess the role of the Th1 and Th2 cellular response in the etiology of endometriosis observed in a rat model, with the use of the RESAN immunomodulator. Materials and Methods. A comparative analysis of cytokines in blood serum typical of Th1 (TNF-α and INF-γ) and Th2 (IL-4, IL-6, IL-10) cell response in groups of rats, in which RESAN preparation was used as prophylaxis (Gr. I) or treatment (Gr. II) of endometriosis. Results. The results indicated an increase in the level of cytokines in blood serum typical of Th2 cell response by comparing the second and third stages of the experiment in the second group of rats and a decrease in IL-4 and IL-10 between III and IV stages. There was a significant difference in cytokine levels during the third stage of the experiment by comparing I and II groups of rats. In the III group of rats, levels of IL-10 significantly increased between the II and III stages of the experiment. Conclusion. RESAN preparation shows Th2 cell response, inhibiting the development of endometriosis in a rat model. Due to successful prophylactic action, one may speculate that RESAN vaccine may be effective as a complementary treatment after surgical excision. K. Szymanowski, J. Niepsuj-Biniaś, A. Dera-Szymanowska, M. Wołuń-Cholewa, A. Yantczenko, E. Florek, T. Opala, M. Murawski, and K. Wiktorowicz Copyright © 2013 K. Szymanowski et al. All rights reserved. Frontomaxillary Facial Angle Measurement in Screening for Trisomy 18 at 11 + 0 to 13 + 6 Weeks of Pregnancy: A Double-Centre Study Tue, 01 Oct 2013 10:04:48 +0000 Objective. The aim of this study was to evaluate the effectiveness of prenatal screening for trisomy 18 with the use of the frontomaxillary facial angle (FMF angle) measurement. Material and Methods. The study involved 1751 singleton pregnancies at 11–13 + 6 weeks, examined between 2007 and 2011. Serum PAPP-A and free beta-hCG levels were assessed, and crown-rump length, nuchal translucency, and FMF angle were measured in all patients. 1350 fetuses with known follow-up were included in the final analysis. Results. Highly significant () negative correlation between the CRL and the FMF angle was found. There were 30 fetuses with trisomy 18. FMF angle was highly significantly larger () in fetuses with trisomy 18 as compared to chromosomally normal fetuses. Two models of first trimester screening were compared: Model 1 based on maternal age, NT, and first trimester biochemistry test (DR 80–85% and FPR 0.3–0.6%), and Model 2 = Model 1 + FMF angle measurement (DR 87.3–93.3% and FPR 0.8–1.3%). Conclusions. The use of FMF angle measurement increases the effectiveness of the screening for trisomy 18. Introduction of the FMF angle as an independent marker for fetal trisomy 18 risk requires further prospective research in large populations. Bartosz Czuba, Wojciech Cnota, Agata Wloch, Piotr Wegrzyn, Krzysztof Sodowski, Miroslaw Wielgos, and Dariusz Borowski Copyright © 2013 Bartosz Czuba et al. All rights reserved. 2-Hour Postload Serum Glucose Levels and Maternal Blood Pressure as Independent Predictors of Birth Weight in “Appropriate for Gestational Age” Neonates in Healthy Nondiabetic Pregnancies Wed, 18 Sep 2013 08:49:22 +0000 Introduction. Increased neonatal birth weight (NBW), often associated with diabetic pregnancies, is a recognized indicator of childhood obesity and future metabolic risk. Predictors of NBW in healthy non-diabetic pregnancies are not yet established. Here, we investigated the association of maternal parameters of healthy non-diabetic mothers with NBW of their “appropriate-for-gestational age” neonates. Methods. The study involved 36 healthy mother/infant pairs. Examined parameters included NBW, maternal age, first and last trimester (BMI), weight gain, fasting serum lipids and glucose, 2-hour postload glucose levels and blood pressure. Results. Postload-glucose levels were significantly higher in mothers of heavier neonates. ANOVA results indicated that 15% increase in postload-glucose levels corresponded to more than 0.5 Kg increase in NBW in the third tertile. NBW correlated positively with postload glucose levels, and negatively with systolic blood pressure. Regression analysis showed that the main predictors of NBW were postload-glucose levels (, ), followed by systolic blood pressure (, ), together predicting 31.7% NBW variation. Conclusion. This study highlights that increased maternal postload sugar levels and blood pressure, within the normal range, highly predicts NBW of healthy mothers. These findings may provide focus for early dietary intervention measures to avoid future risks to the mother and baby. Jumana Saleh, Lovina Machado, and Zahra Razvi Copyright © 2013 Jumana Saleh et al. All rights reserved. Effect of Supracervical Apposition and Spontaneous Labour on Apoptosis and Matrix Metalloproteinases in Human Fetal Membranes Wed, 11 Sep 2013 11:42:23 +0000 Background. Apoptosis and matrix metalloproteinase (MMP-9) are capable of hydrolysing components of the extracellular matrix and weakening the fetal membranes which leads to eventual rupture, a key process of human parturition. The aim of this study was to determine the effect of supracervical apposition and spontaneous labour on apoptosis and MMP-9 in human fetal membranes at term. Methods. Fetal membranes were obtained from term non-labouring supracervical site (SCS) and compared to (i) a paired distal site (DS) or (ii) site of rupture (SOR) after spontaneous labour onset. Results. The expression of the proapoptotic markers Bax, Smac, Fas, FasL, caspase-3, and PARP, was significantly higher in the non-labouring SCS chorion compared to paired DS. Bax, Smac, FasL, caspase-3, and PARP staining was higher in the non-labouring SCS fetal membranes than that in the post-labour SOR. MMP-9 expression and activity were higher in the post-labour SOR fetal membranes compared to non-labouring SCS fetal membranes. Conclusion. Components of the apoptotic signalling pathways and MMP-9 may play a role in rupture and labour. Non-labouring SCS fetal membranes display altered morphology and altered apoptotic biochemical characteristics in preparation for labour, while the laboured SOR displays unique MMP characteristics. Mahalia Chai, Susan P. Walker, Clyde Riley, Gregory E. Rice, Michael Permezel, and Martha Lappas Copyright © 2013 Mahalia Chai et al. All rights reserved. Maternal Plasma miRNAs Expression in Preeclamptic Pregnancies Mon, 09 Sep 2013 12:15:46 +0000 Objective. Preeclampsia (PE) is a pregnancy-specific syndrome and one of the leading causes of maternal and fetal morbidity and mortality. The pathophysiological mechanisms of PE remain poorly known. Recently, circulating miRNAs are considered as potential useful noninvasive biomarkers. The aim of this study was to identify differentially expressed plasma miRNAs in preeclamptic pregnancies compared with normal pregnancies. Methods. Maternal plasma miRNA expression profiles were detected by SOLiD sequencing. Differential expressions between mPE/sPE and control group were found. Next, four differentially expressed plasma miRNAs were chosen to validate their expression in other large scale samples by real-time PCR. Results. In terms of sequencing results, we identified that 51 miRNAs were differentially expressed. Four differentially expressed plasma miRNAs (miR-141, miR-144, miR-221, and miR-29a) were selected to validate the sequencing results. RT-PCR data confirmed the reliability of sequencing results. The further statistical analysis showed that maternal plasma miR-141 and miR-29a are significantly overexpressed in mPE (). Maternal plasma miR-144 is significantly underexpressed in mPE and sPE (). Conclusions. Results showed that there were differentially expressed maternal plasma miRNAs in patients with preeclampsia. These plasma miRNAs might be used as notable biomarkers for diagnosis of preeclampsia. Hailing Li, Qinyu Ge, Li Guo, and Zuhong Lu Copyright © 2013 Hailing Li et al. All rights reserved. Clinical Prediction of Deeply Infiltrating Endometriosis before Surgery: Is It Feasible? A Review of the Literature Thu, 05 Sep 2013 13:41:35 +0000 Background. Endometriosis is a chronic benign gynecologic disease that can cause pelvic pain and infertility affecting almost 10% of reproductive-age women. Deeply infiltrating endometriosis (DIE) is a specific entity responsible for painful symptoms which are related to the anatomic location of the lesions. Definitive diagnosis requires surgery, and histological confirmation is advisable. The aim of this paper is to review the current literature regarding the possibility of diagnosing DIE accurately before surgery. Despite its low sensitivity and specificity, vaginal examination and evaluation of specific symptoms should not be completely omitted as a basic diagnostic tool in detecting endometriosis and planning further therapeutic interventions. Recently, transvaginal ultrasound (TVUS) has been reported as an excellent tool to diagnose DIE lesions in different locations (rectovaginal septum, retrocervical and paracervical areas, rectum and sigmoid, and vesical wall) with good accuracy. Conclusion. There are neither sufficiently sensitive and specific signs and symptoms nor diagnostic tests for the clinical diagnosis of DIE, resulting in a great delay between onset of symptoms and diagnosis. Digital examination, in addition to TVS, may help to gain better understanding of the anatomical extent and dimension of DIE which is of crucial importance in defining the best surgical approach. Márcia Mendonça Carneiro, Ivone Dirk de Sousa Filogônio, Luciana Maria Pyramo Costa, Ivete de Ávila, and Márcia Cristina França Ferreira Copyright © 2013 Márcia Mendonça Carneiro et al. All rights reserved. Comparison between Amnisure Placental Alpha Microglobulin-1 Rapid Immunoassay and Standard Diagnostic Methods for Detection of Rupture of Membranes Sun, 01 Sep 2013 09:00:53 +0000 Objective. To determine the diagnostic accuracy of placental alpha microglobulin-1 assay and standard diagnostic methods for detecting rupture of membrane. Study Design. Prospective diagnostic study, between June 2011 to November 2011 at a tertiary centre. Initial evaluation included both the standard diagnostic methods for rupture of membranes and placental alpha microglobulin-1 immunoassay. The actual rupture of membranes was diagnosed on review of the medical records after delivery (absence of membrane or a positive pad chart). Main Outcome Measures. Placental alpha microglobulin-1 immunoassay and standard diagnostic methods for diagnosis of rupture of membrane. Results. A total of 211 patients were recruited. At initial presentation, 187 patients (88.6%) had ruptured membranes, while 24 patients (11.4%) had intact membranes. Placental alpha microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 95.7% (179 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (179 of 179), and negative predictive value of 75.0% (24 of 32). By comparison, the conventional standard diagnostic methods had a sensitivity of 78.1% (146 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (146 of 146), and negative predictive value of 36.9% (24 of 65) in diagnosing rupture of membrane. Conclusion. Placental alpha-microglobulin-1 immunoassay is a rapid and accurate method for confirming the diagnosis of rupture of membrane. It was superior to conventional standard diagnostic methods (pooling, nitrazine, and ferning), the nitrazine test alone or fern test alone. Beng Kwang Ng, Pei Shan Lim, Mohamad Nasir Shafiee, Nur Azurah Abdul Ghani, Nor Azlin Mohamed Ismail, Mohd Hashim Omar, and Muhammad Abdul Jamil Muhammad Yassin Copyright © 2013 Beng Kwang Ng et al. All rights reserved. Endometrial Polyps in Women Affected by Levothyroxine-Treated Hypothyroidism—Histological Features, Immunohistochemical Findings, and Possible Explanation of Etiopathogenic Mechanism: A Pilot Study Thu, 22 Aug 2013 11:01:48 +0000 The aim of the study was to investigate the possible overexpression of estrogen (ERs) and progesterone (PRs) receptors both in EPs glandular and stromal cells in postmenopausal women with levothyroxine-treated hypothyroidism in comparison to EPs detected in women with physiological thyroid hormone levels. During the study period (January-February 2013) 22 patients were eligible (12 treated, 10 controls). The two groups were homogenous for general, EPs sonographic and hysteroscopic features. None of the cases of atypia was found. Immunohistochemistry showed that the two groups were similar for ERs and PRs intensity rates in EPs glandular cells despite a trend of ERs percentage expression more than 60% in 2/3 of treated patients versus 1/3 of controls. In stromal EPs components, ERs intensity was high positive in 10 (83,3%) treated cases while it was high positive in 1 control (10%). Percentage of ERs stromal expression showed a different trend between the two groups despite a borderline statistical significance. Our hypothesis is based on a possible double action of hypothyroidism and thyroxine intake: the subclinical TSH increased levels and its possible circadian oscillation could stimulate the endometrial TSHRs (increasing type 2 DIO activity); the circulating levels of exogenous thyroxine could be locally metabolized in active form by type 2 DIO stimulating ERs. Carlo Saccardi, Salvatore Gizzo, Kathrin Ludwig, Maria Guido, Mara Scarton, Michele Gangemi, Raffaele Tinelli, and Pietro Salvatore Litta Copyright © 2013 Carlo Saccardi et al. All rights reserved. Levels of Key Enzymes of Methionine-Homocysteine Metabolism in Preeclampsia Tue, 20 Aug 2013 11:57:17 +0000 Objective. To evaluate the role of key enzymes in the methionine-homocysteine metabolism (MHM) in the physiopathology of preeclampsia (PE). Methods. Plasma and placenta from pregnant women (32 controls and 16 PE patients) were analyzed after informed consent. Protein was quantified by western blot. RNA was obtained with RNA purification kit and was quantified by reverse transcritase followed by real-time PCR (RT-qPCR). Identification of the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association analysis was carried out using Fisher’s exact test. Statistical analysis was performed using a Mann-Whitney test. Results. RNA expression of MTHFR and MTR was significantly higher in patients with PE as compared with controls. Protein, SAM, and SAH levels showed no significant difference between preeclamptic patients and controls. No statistical differences between controls and PE patients were observed with the different SNPs studied. Conclusion. The RNA expression of MTHFR and MTR is elevated in placentas of PE patients, highlighting a potential compensation mechanism of the methionine-homocysteine metabolism in the physiopathology of this disease. Alejandra Pérez-Sepúlveda, Pedro P. España-Perrot, Ximena Fernández B, Verónica Ahumada, Vicente Bustos, José Antonio Arraztoa, Aneta Dobierzewska, Horacio Figueroa-Diesel, Gregory E. Rice, and Sebastián E. Illanes Copyright © 2013 Alejandra Pérez-Sepúlveda et al. All rights reserved. Maternal Deaths in NSW (2000–2006) from Nonmedical Causes (Suicide and Trauma) in the First Year following Birth Mon, 19 Aug 2013 10:10:01 +0000 Introduction. Trauma, including suicide, accidental injury, motor traffic accidents, and homicides, accounts for 73% of all maternal deaths (early and late) in NSW annually. Late maternal deaths are underreported and are not as well documented or acknowledged as early deaths. Methods. Linked population datasets from births, hospital admissions, and death registrations were analysed for the period from 1 July 2000 to 31 December 2007. Results. There were 552 901 births and a total of 129 maternal deaths. Of these deaths, 37 were early deaths (early MMR of 6.7/100 000) and 92 occurred late (late MMR of 16.6/100 000). Sixty-seven percent of deceased women had a mental health diagnosis and/or a mental health issue related to substance abuse noted. A notable peak in deaths appeared to occur from 9 to 12 months following birth with the odds ratio of a woman dying of nonmedical causes within 9–12 months of birth being 3.8 (95% CI 1.55–9.01) when compared to dying within the first 3 months following birth. Conclusion. Perinatal services are often constructed to provide short-term support. Long-term identification and support of women at particular risk of maternal death due to suicide and trauma in the first year following birth may help lower the incidence of late maternal deaths. Charlene Thornton, Virginia Schmied, Cindy-Lee Dennis, Bryanne Barnett, and Hannah Grace Dahlen Copyright © 2013 Charlene Thornton et al. All rights reserved. Hemoglobin Concentration and Pregnancy Outcomes: A Systematic Review and Meta-Analysis Thu, 25 Jul 2013 14:46:06 +0000 Objective. To conduct a systematic review and meta-analysis of hemoglobin effect on the pregnancy outcomes. Methods. We searched MEDLINE and SCOPUS from January 1, 1990 to April 10, 2011. Observational studies addressing association between hemoglobin and adverse pregnancy outcomes were selected. Two reviewers independently extracted data. A mixed logistic regression was applied to assess the effects of hemoglobin on preterm birth, low birth weight, and small for gestational age. Results. Seventeen studies were included in poolings. Hemoglobin below 11 g/dL was, respectively, 1.10 (95% CI: 1.02–1.19), 1.17 (95% CI: 1.03–1.32), and 1.14 (95% CI: 1.05–1.24) times higher risk of preterm birth, low birth weight, and small for gestational age than normal hemoglobin in the first trimester. In the third trimester, hemoglobin below 11 g/dL was 1.30 (95% CI: 1.08–1.58) times higher risk of low birth weight. Hemoglobin above 14 g/dL in third trimester decreased the risk of preterm term with ORs of 0.50 (95% CI: 0.26–0.97), but it might be affected by publication bias. Conclusions. Our review suggests that hemoglobin below 11 g/dl increases the risk of preterm birth, low birth weight, and small gestational age in the first trimester and the risk of low birth weight in the third trimester. Bunyarit Sukrat, Chumpon Wilasrusmee, Boonying Siribumrungwong, Mark McEvoy, Chusak Okascharoen, John Attia, and Ammarin Thakkinstian Copyright © 2013 Bunyarit Sukrat et al. All rights reserved. Does Cryopreservation of Ovarian Tissue Affect the Distribution and Function of Germinal Vesicle Oocytes Mitochondria? Wed, 17 Jul 2013 09:56:17 +0000 The aim of this study was to evaluate mitochondrial alteration and ATP content of germinal vesicle (GV) oocytes isolated from fresh and vitrified ovaries. After superovulation, the ovaries from adult mice were collected and divided into control and vitrified groups. GV oocytes were isolated mechanically from each group. Half were cultured for 24 hours and their maturation was assessed. Metaphase II oocytes were collected and submitted to in vitro fertilization and their fertilization rates and development to the blastocyst stage were evaluated. In the remaining GV oocytes, ATP levels were quantified, and mitochondrial distribution, mitochondrial membrane potential, and intracellular free calcium were detected with rhodamine 123, JC-1 and Flou-4 AM staining, using laser-scanning confocal microscopy. Maturation and fertilization rates of GV oocytes and the developmental rates of subsequent embryos were significantly lower in vitrified samples (). The ATP content and Ca2+ levels differed significantly in fresh and vitrified GV oocytes (). Most mitochondria were seen as large and homogenous aggregates (66.6%) in fresh GV oocytes compared to vitrified oocytes (50%). No significant differences in mitochondrial membrane potential were found between the groups. The lower maturation and fertilization rates of GV oocytes from vitrified ovaries may be due to changes in their mitochondrial function and distribution. Mojdeh Salehnia, Virpi Töhönen, Saeed Zavareh, and Jose Inzunza Copyright © 2013 Mojdeh Salehnia et al. All rights reserved. Autophagy and Human Parturition: Evaluation of LC3 Expression in Placenta from Spontaneous or Medically Induced Onset of Labor Tue, 16 Jul 2013 12:52:12 +0000 Induction of labor is one of the most used procedures in obstetrics, performed to achieve vaginal delivery through cervical ripening and stimulation of uterine contractions. We investigated the impact of induction of labor upon placental autophagy, a catabolic pathway activated in response to alteration of the physiological intracellular conditions. We collected 28 singleton placentas at the time of uncomplicated term vaginal delivery (7 spontaneous onset of labor, 21 induced labor). Autophagy was evaluated by immunohistochemistry, immunofluorescence, and immunoblotting. No significant difference in the autophagy expression was found between spontaneous or induced onset of labor. We found an inverse relationship between autophagy expression and the maternal prepregnancy body mass index, irrespective of the mode of labor onset. This result could be related to the nutritional maternal habits before and throughout pregnancy rather than rapid metabolic changes during labor. Laura Avagliano, Eleonora Virgili, Chiara Garò, Federica Quadrelli, Patrizia Doi, Michele Samaja, Gaetano Pietro Bulfamante, and Anna Maria Marconi Copyright © 2013 Laura Avagliano et al. All rights reserved. Interinstitutional Variation of Caesarean Delivery Rates According to Indications in Selected Obstetric Populations: A Prospective Multicenter Study Tue, 25 Jun 2013 17:34:23 +0000 The aim of the study was to identify which groups of women contribute to interinstitutional variation of caesarean delivery (CD) rates and which are the reasons for this variation. In this regard, 15,726 deliveries from 11 regional centers were evaluated using the 10-group classification system. Standardized indications for CD in each group were used. Spearman’s correlation coefficient was used to calculate (1) relationship between institutional CD rates and relative sizes/CD rates in each of the ten groups/centers; (2) correlation between institutional CD rates and indications for CD in each of the ten groups/centers. Overall CD rates correlated with both CD rates in spontaneous and induced labouring nulliparous women with a single cephalic pregnancy at term (). Variation of CD rates was also dependent on relative size and CD rates in multiparous women with previous CD, single cephalic pregnancy at term (). As for the indications, “cardiotocographic anomalies” and “failure to progress” in the group of nulliparous women in spontaneous labour and “one previous CD” in multiparous women previous CD correlated significantly with institutional CD rates (, , and , resp.). These results supported the conclusion that only selected indications in specific obstetric groups accounted for interinstitutional variation of CD rates. Gianpaolo Maso, Monica Piccoli, Marcella Montico, Lorenzo Monasta, Luca Ronfani, Sara Parolin, Carmine Gigli, Daniele Domini, Claudio Fiscella, Sara Casarsa, Carlo Zompicchiatti, Michela De Agostini, Attilio D’Atri, Raffaela Mugittu, Santo La Valle, Cristina Di Leonardo, Valter Adamo, Mara Fracas, Giovanni Del Frate, Monica Olivuzzi, Silvio Giove, Maria Parente, Daniele Bassini, Simona Melazzini, Secondo Guaschino, Caterina Businelli, Franco G. Toffoletti, Diego Marchesoni, Alberto Rossi, Sergio Demarini, Laura Travan, Giorgio Simon, Sandro Zicari, Giorgio Tamburlini, and Salvatore Alberico Copyright © 2013 Gianpaolo Maso et al. All rights reserved. Effects of Processing and Storage on Pediococcus pentosaceus SB83 in Vaginal Formulations: Lyophilized Powder and Tablets Mon, 17 Jun 2013 18:43:51 +0000 Vaginal probiotics have an important role in preventing the colonization of the vagina by pathogens. This study aimed to investigate different formulations with Pediococcus pentosaceus SB83 (lyophilized powder and tablets with and without retarding polymer) in order to verify its stability and antilisterial activity after manufacture and during storage. The bacteriocinogenic activity of P. pentosaceus SB83 against Listeria monocytogenes was evaluated in simulated vaginal fluid. Suspension of Pediococcus pentosaceus SB83 reduced the pathogen only after 2 h and the lyophilized bacteria after 24 h of contact, and, in the tablets, P. pentosaceus SB83 lost the antimicrobial activity. The pH of simulated vaginal fluid decreased for all the tested conditions. As lyophilized powder demonstrated better results concerning antimicrobial activity, this formulation was selected to evaluate the antilisterial activity during the 12 months of storage. During storage at room temperature, lyophilized bacteria totally inhibited the pathogen only until one month of storage. At 4°C, P. pentosaceus SB83 showed antimicrobial activity during all the time of storage investigated. Therefore, the better formulation of P. pentosaceus SB83 is the lyophilized powder stored at 4°C, which may be administered intravaginally as a washing solution. Sandra Borges, Paulo Costa, Joana Silva, and Paula Teixeira Copyright © 2013 Sandra Borges et al. All rights reserved. Comparison of Hay’s Criteria with Nugent’s Scoring System for Diagnosis of Bacterial Vaginosis Thu, 13 Jun 2013 08:55:37 +0000 Although Nugent’s criterion is considered as the gold standard for the diagnosis of bacterial vaginosis (BV), the method requires an experienced slide reader and considerable time and skill. In this study, we compared the method of Hay and Ison with Nugent’s scoring criteria. Vaginal specimens were collected from a total of 213 women, presenting with or without the symptoms of vaginitis. Diagnosis of BV was done using Nugent’ and Hay’s method. Sensitivity, specificity, and predictive values for positive and negative test were calculated for Hay’s method using Nugent’s method as the gold standard. We diagnosed 70 cases (32.86%) of BV by Nugent’s method and 87 (40.85%) cases by the Hay’s method. Sensitivity, specificity, predictive value of positive result, predictive value of negative result, and Kappa value when evaluating Hay’s criteria using Nugent’s criteria as the gold standard were ≥97.2%, ≥88.1%, ≥80.4%, ≥97.1%, and ≥0.830, respectively, when Hay’s grade II and/or Nugent’s intermediate score were considered either as negative or positive or excluded. Using Nugent score for the intermediate group is the most difficult. Hay’s method shows good agreement with the gold standard method of Nugent et al. and can be used as an alternative to Nugent’s criteria in busy tertiary care hospitals. Rohit Chawla, Preena Bhalla, Sanjim Chadha, Sujatha Grover, and Suneela Garg Copyright © 2013 Rohit Chawla et al. All rights reserved. Metabolomics Application in Maternal-Fetal Medicine Sun, 09 Jun 2013 11:51:57 +0000 Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future. Vassilios Fanos, Luigi Atzori, Karina Makarenko, Gian Benedetto Melis, and Enrico Ferrazzi Copyright © 2013 Vassilios Fanos et al. All rights reserved. Identification of Women for Referral to Colposcopy by Neural Networks: A Preliminary Study Based on LBC and Molecular Biomarkers Wed, 03 Oct 2012 10:31:54 +0000 Objective of this study is to investigate the potential of the learning vector quantizer neural network (LVQ-NN) classifier on various diagnostic variables used in the modern cytopathology laboratory and to build an algorithm that may facilitate the classification of individual cases. From all women included in the study, a liquid-based cytology sample was obtained; this was tested via HPV DNA test, E6/E7 HPV mRNA test, and p16 immunostaining. The data were classified by the LVQ-NN into two groups: CIN-2 or worse and CIN-1 or less. Half of the cases were used to train the LVQ-NN; the remaining cases (test set) were used for validation. Out of the 1258 cases, cytology identified correctly 72.90% of the CIN-2 or worst cases and 97.37% of the CIN-1 or less cases, with overall accuracy 94.36%. The application of the LVQ-NN on the test set allowed correct classification for 84.62% of the cases with CIN-2 or worse and 97.64% of the cases with CIN-1 or less, with overall accuracy of 96.03%. The use of the LVQ-NN with cytology and the proposed biomarkers improves significantly the correct classification of cervical precancerous lesions and/or cancer and may facilitate diagnosis and patient management. Petros Karakitsos, Charalampos Chrelias, Abraham Pouliakis, George Koliopoulos, Aris Spathis, Maria Kyrgiou, Christos Meristoudis, Aikaterini Chranioti, Christine Kottaridi, George Valasoulis, Ioannis Panayiotides, and Evangelos Paraskevaidis Copyright © 2012 Petros Karakitsos et al. All rights reserved. Quantitative Proteomic (iTRAQ) Analysis of 1st Trimester Maternal Plasma Samples in Pregnancies at Risk for Preeclampsia Tue, 10 Apr 2012 13:58:58 +0000 A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for the detection of new preeclampsia screening markers. Varaprasad Kolla, Paul Jenö, Suzette Moes, Olav Lapaire, Irene Hoesli, and Sinuhe Hahn Copyright © 2012 Varaprasad Kolla et al. All rights reserved. Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells Tue, 06 Dec 2011 13:50:19 +0000 The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on alkaline phosphatase, and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28, KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future. Irma Virant-Klun, Thomas Skutella, Martin Stimpfel, and Jasna Sinkovec Copyright © 2011 Irma Virant-Klun et al. All rights reserved. Association of Angiotensin-Converting Enzyme Intron 16 Insertion/Deletion and Angiotensin II Type 1 Receptor A1166C Gene Polymorphisms with Preeclampsia in South East of Iran Tue, 26 Jul 2011 19:05:26 +0000 Some evidence suggests that a variety of genetic factors contributed in pathogenesis of the preeclampsia. The aim of this study was to assess the association between the angiotensin-converting enzyme (ACE) I/D and angiotensin II type1 receptor A1166C polymorphisms with preeclampsia. This study was performed in 125 preeclamptic pregnant women and 132 controls. The I/D Polymorphism of the ACE gene was assessed by polymerase chain reaction and the A1166C Polymorphism of the AT1R gene was determined by restriction fragment length polymorphism. The genotype and allele frequencies of I/D polymorphism differed between two groups. The risk of preeclampsia was 3.2-fold in pregnant women with D allele (OR, 3.2 [95% CI, 1.1 to 3.8]; ). The distribution of the AT1R gene A1166C polymorphism was similar in affected and control groups. Our results supported that presence of the I/D polymorphism of ACE gene is a marker for the increased risk of preeclampsia. Saeedeh Salimi, Mojgan Mokhtari, Minoo Yaghmaei, Mohammad Jamshidi, and Anoosh Naghavi Copyright © 2011 Saeedeh Salimi et al. All rights reserved. Clinical Therapeutics in Pregnancy Wed, 06 Jul 2011 15:53:15 +0000 Most drugs are not tested for use during pregnancy, consequently, labeling, which may include information about fetal safety, includes nothing about dosing, efficacy, or maternal safety. Yet these are concerns of health care providers considering treatment of disease during pregnancy. Therefore, the practitioner treats the pregnant woman with the same dose recommended for use in adults (typically men) or may decide not to treat the disease at all. However, is the choice of not treating a woman during pregnancy better than dealing with the challenges which accompany treatment? This paper, which summarizes metabolic and physiologic changes induced by pregnancy, illustrates that standard adult dosing is likely to be incorrect during pregnancy. Maisa N. Feghali and Donald R. Mattison Copyright © 2011 Maisa N. Feghali and Donald R. Mattison. All rights reserved. Differential Expression of MicroRNAs between Eutopic and Ectopic Endometrium in Ovarian Endometriosis Wed, 10 Mar 2010 10:52:09 +0000 Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identified in silico their predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopic versus eutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology. Nicoletta Filigheddu, Ilaria Gregnanin, Paolo E. Porporato, Daniela Surico, Beatrice Perego, Licia Galli, Claudia Patrignani, Andrea Graziani, and Nicola Surico Copyright © 2010 Nicoletta Filigheddu et al. All rights reserved.