BioMed Research International: Obstetrics and Gynecology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Cervical Cancer Cell Line Secretome Highlights the Roles of Transforming Growth Factor-Beta-Induced Protein ig-h3, Peroxiredoxin-2, and NRF2 on Cervical Carcinogenesis Thu, 02 Feb 2017 06:01:56 +0000 Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV−), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis. Georgia Kontostathi, Jerome Zoidakis, Manousos Makridakis, Vasiliki Lygirou, George Mermelekas, Theofilos Papadopoulos, Konstantinos Vougas, Alexios Vlamis-Gardikas, Peter Drakakis, Dimitrios Loutradis, Antonia Vlahou, Nicholas P. Anagnou, and Kalliopi I. Pappa Copyright © 2017 Georgia Kontostathi et al. All rights reserved. Effects of Aspirin and Intrauterine Balloon on Endometrial Repair and Reproductive Prognosis in Patients with Severe Intrauterine Adhesion: A Prospective Cohort Study Mon, 30 Jan 2017 08:26:11 +0000 This study aimed to investigate the effects of estrogen in combination with aspirin and intrauterine balloon on the uterine endometrial repair and reproductive prognosis in patients after surgery for severe intrauterine adhesion (sIUA). We prospectively recruited 114 patients with sIUA. Intrauterine device (IUD) was placed and oral estrogen was administered after surgery. Patients were divided into control group and aspirin group. In addition, patients in aspirin group were subdivided into nonballoon group and balloon group. Results showed that, after therapy, the increase in endometrial thickness of aspirin groups was superior to control group (). The scores of intrauterine adhesion and menstruation were significantly improved in balloon group as compared to nonballoon group and control group, and significant differences were also observed between nonballoon group and control group (). Of 97 patients, 44.3% became pregnant after surgery, the live birth rate was 27.8%, and the miscarriage rate was 37.2%, but there were no significant differences among three groups (). Thus, aspirin may promote the uterine endometrial growth and repair after surgery for sIUA, and IUD in combination with intrauterine balloon may reduce the recurrence of intrauterine adhesion, but their effect on the reproductive prognosis is required to be further studied. Yuqing Chen, Lixiang Liu, Yuanna Luo, Minghui Chen, Yang Huan, and Ruili Fang Copyright © 2017 Yuqing Chen et al. All rights reserved. Pregnancy during Adolescence and Associated Risks: An 8-Year Hospital-Based Cohort Study (2007–2014) in Romania, the Country with the Highest Rate of Teenage Pregnancy in Europe Wed, 04 Jan 2017 13:40:52 +0000 Aim. To determine pregnancy and delivery outcomes among teenagers. Materials and Methods. An 8-year retrospective comparative hospital-based cohort study is analysing singleton pregnancy comorbidities and delivery parameters of a teenage group under the age of 20 compared with a young adult group 20–24 years of age in a university hospital. Results. Teenage is a risk factor for preterm birth <37 weeks (1.21 [1.08–1.35]), foetal growth restriction (1.34 [1.21–1.48]), episiotomy (1.27 [1.21–1.34]), uterine revision (1.15 [1.06–1.25]), APGAR <7 at 1 min (2.42 [1.21–1.67]), cephalopelvic disproportion (1.26 [1.07–1.48]), and postpartum haemorrhage (1.42 [1.25–1.62]); however, caesarean delivery occurs less frequently in teenagers than in adults (0.75 [0.70–0.80]). The following comorbidities are risk factors for teenage pregnancy (risk ratio [CI 95%]): anaemia (1.13 [1.10–1.17]), low urinary tract infection (1.10 [1.03–1.18]), pediculosis (2.42 [1.90–3.00]), anogenital condyloma (1.50 [1.04–2.17]), and trichomoniasis (1.74 [1.12–2.68]). The risks for hepatitis B and hepatitis C, premature rupture of membranes, and placenta praevia were lower compared with those in the young adult group, respectively, 0.43 (0.26–0.71), 0.90 (0.85–0.96), and 0.29 (0.20–0.41), while the risk for gestational diabetes and preeclampsia were the same in both groups. Conclusion. Considering the high risks for teenage pregnancy, this information should be provided to pregnant adolescent women and their caregivers. Demetra-Gabriela Socolov, Magdalena Iorga, Alexandru Carauleanu, Ciprian Ilea, Iolanda Blidaru, Lucian Boiculese, and Razvan-Vladimir Socolov Copyright © 2017 Demetra-Gabriela Socolov et al. All rights reserved. Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway Tue, 20 Dec 2016 11:28:27 +0000 Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β, β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway. Jingjing Lu, Ying Xu, Xuan Wei, Zhe Zhao, Jing Xue, and Peishu Liu Copyright © 2016 Jingjing Lu et al. All rights reserved. Perinatal and Neonatal Outcomes of Patients Who Were Diagnosed with Neural Tube Defect in Midtrimester Fetal Ultrasound Scan and Refused Request for Termination of Pregnancy Wed, 23 Nov 2016 14:36:24 +0000 Objectives. In this study, we aimed to demonstrate the perinatal and neonatal outcomes of patients who were diagnosed with neural tube defect (NTD) in the midtrimester fetal ultrasound scan and refused the request for termination of pregnancy. Material and Methods. The records of 69 patients, for whom NTD was detected in the midtrimester fetal ultrasound scan and who preferred the continuation of the pregnancy after comprehensive counselling about the possible prognosis and treatment options during the period between January 2011 and February 2016, were reviewed retrospectively. Results. Of these patients, 66.7% were 25–35 years old; 95.7% were multiparous; and 1.4% had a history of a fetus having NTD in previous pregnancies. There were 7 (10.1%) neonatal deaths in these patients. Meningomyelocele closure procedure was the most performed surgery in the postnatal period (92%). Of these patients, 30.7% had paraplegia; 51.6% had neurogenic bladder; and 6.4% had infections due to surgery. Conclusion. The results of this study demonstrated perinatal and neonatal outcomes of fetuses with NTD who were not terminated by the preference of the family in midtrimester. The experience of our centre would be beneficial as a tool for nondirective counselling of these patients when considering the antenatal/postnatal care options and postnatal prognosis. Rauf Melekoglu, Sevil Eraslan, Ebru Celik, and Yavuz Simsek Copyright © 2016 Rauf Melekoglu et al. All rights reserved. Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis Wed, 16 Nov 2016 07:03:39 +0000 Background. Despite the great achievements in the treatment of advanced-stage ovarian cancer, it is still a severe condition with an unfavorable 5-year survival rate. Statins have been suggested to reduce the risk of several cancers beyond their cholesterol-lowing effects. However, the prognostic significance of statins in patients with advanced-stage ovarian cancer remains controversial. Methods. A retrospective study was performed to evaluate the association between statin intake and overall survival (OS) among patients with advanced-stage ovarian cancer. Patients who underwent cytoreductive surgery followed by courses of intravenous chemotherapy were matched through a propensity score analysis. Results. A total of 60 propensity-matched patients were included. Women in statin group showed a similar OS than the nonstatin counterparts (), whereas residual tumor was significantly associated with better OS () and was an independent factor that associated with OS (, hazard ratio = 5.460, and 95% confidence interval: 1.894 to 15.742) in multivariable analysis. Conclusions. Our results suggested that statin usage was not associated with improved OS in patients with advanced-stage ovarian cancer undergoing surgery and chemotherapy. Considering the retrospective nature and the relative small sample size of the study, further prospective studies and random control trials are needed. Hong-Yu Chen, Qian Wang, Qiu-Hong Xu, Li Yan, Xue-Feng Gao, Yan-Hong Lu, and Li Wang Copyright © 2016 Hong-Yu Chen et al. All rights reserved. The Impact of Endometriosis on the Health of Women 2016 Tue, 01 Nov 2016 09:42:49 +0000 Liselotte Mettler, Dietmar Schmidt, and Peter Maher Copyright © 2016 Liselotte Mettler et al. All rights reserved. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale Wed, 26 Oct 2016 08:05:26 +0000 Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (). A value <0.001 was considered statistically significant. Results. In mestizo women, the highest were obtained in physical and mental exhaustion (PME) () and the lowest ones in anxiety (). In Afro-Colombian women, an average score of for PME and for anxiety was gotten. Indigenous women obtained an increased average score for PME (). The lowest score was evidenced in depressive mood (), which is different from other Colombian women (). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct. Alvaro Monterrosa-Castro, Katherin Portela-Buelvas, Heidi C. Oviedo, Edwin Herazo, and Adalberto Campo-Arias Copyright © 2016 Alvaro Monterrosa-Castro et al. All rights reserved. Patient Perceptions of Open, Laparoscopic, and Robotic Gynecological Surgeries Thu, 20 Oct 2016 13:42:34 +0000 Objective. To investigate patient knowledge and attitudes toward surgical approaches in gynecology. Design. An anonymous Institutional Review Board (IRB) approved questionnaire survey. Patients/Setting. A total of 219 women seeking obstetrical and gynecological care in two offices affiliated with an academic medical center. Results. Thirty-four percent of the participants did not understand the difference between open and laparoscopic surgeries. 56% of the participants knew that laparoscopy is a better surgical approach for patients than open abdominal surgeries, while 37% thought that laparoscopy requires the surgeon to have a higher technical skill. 46% of the participants do not understand the difference between laparoscopic and robotic procedures. 67.5% of the participants did not know that the surgeon moves the robot’s arms to perform the surgery. Higher educational level and/or history of previous abdominal surgeries were associated with the highest rates of answering all the questions correctly (), after controlling for age and race. Conclusions. A substantial percentage of patients do not understand the difference between various surgical approaches. Health care providers should not assume that their patients have an adequate understanding of their surgical options and accordingly should educate them about those options so they can make truly informed decisions. Mohamad Irani, Cheruba Prabakar, Sepide Nematian, Nitasha Julka, Devika Bhatt, and Pedram Bral Copyright © 2016 Mohamad Irani et al. All rights reserved. Activin A Stimulates Aromatase via the ALK4-Smad Pathway in Endometriosis Wed, 19 Oct 2016 11:09:01 +0000 Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA. Cumulatively, these data suggest that Activin A promotes the secretion of estradiol from ESCs by increasing the expression of P450arom via the ALK4-Smad pathway. These findings indicate the ALK4-Smad pathway may promote ectopic lesion survival and development. Juan Zheng, Juan Qu, Pinhong Lu, Zhen Hou, Yugui Cui, Yundong Mao, Xiaochen Qi, Hui Ji, and Jiayin Liu Copyright © 2016 Juan Zheng et al. All rights reserved. The Role of Interleukin-18 in Serum and Follicular Fluid during In Vitro Fertilization and Intracytoplasmic Sperm Injection Thu, 22 Sep 2016 13:18:15 +0000 Cytokines are key modulators of the immune system and play an important role in the ovarian cycle. IL-18 levels in serum and follicular fluid were analyzed in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. The cohort study group consisted of 90 women, who were undergoing IVF or ICSI. The body mass index (BMI) was determined in all patients; IL-18 levels were measured in follicular fluid and serum. IL-18 levels in serum were significantly higher than those in follicular fluid. The median level in serum was 162.75 (80.21) pg/mL and that in follicular fluid, 138.24 (91.78) pg/mL. Women undergoing IVF treatment had lower IL-18 levels in serum (median, 151.19 (90.73) pg/mL) than those treated with ICSI (median, 163.57 (89.97) pg/mL). The correlation between IL-18 levels in serum and BMI was statistically significant, as well as the correlation between IL-18 levels in follicular fluid and ovarian stimulation response (). IL-18 was correlated with the response to ovarian stimulation and was the reason for successful pregnancy after IVF or ICSI treatment. Among other cytokines, IL-18 appears to be a promising prognostic marker of success in reproductive treatment and should be evaluated as such in further prospective studies. Veronika Günther, Ibrahim Alkatout, Corinna Fuhs, Ali Salmassi, Liselotte Mettler, Jürgen Hedderich, Nicolai Maass, Mohamed Elessawy, Andreas Gerd Schmutzler, and Christel Eckmann-Scholz Copyright © 2016 Veronika Günther et al. All rights reserved. Safety, Efficiency, and Outcomes of Perineoplasty: Treatment of the Sensation of a Wide Vagina Wed, 17 Aug 2016 09:46:07 +0000 Background. The sensation of a wide vagina is a common problem for women after childbirth. As its etiology is unknown, there is no uniform management strategy. We hypothesized that, rather than vaginal laxity, the cause was level 3 pelvic support deficiency. Methods. This retrospective study compared preoperative and postoperative genital hiatus length, perineal length, and total vaginal length in patients treated with perineoplasty for the sensation of a wide vagina. A telephone survey was used to determine postoperative patient and male partner satisfaction rates. Results. Mean age of patients was 48 (26–68) years; mean body mass index (BMI) was 25.3 (17.6–33.2); and mean parity was 2.5 (2–5). Preoperative and postoperative genital hiatus, perineal length, and total vaginal length were 4.62 and 3.18 (), 3.06 and 4.04 (), and 9.43 and 9.43 (), respectively. At the 6-month follow-up, the success rate of the perineoplasty procedure was 87.9%; according to a visual analog scale, partner satisfaction rate was 92.6%. Ten percent () of patients said they experienced dyspareunia during sexual intercourse at the introitus of the vagina. Conclusion. With low dyspareunia rates, low complication rates, high patient satisfaction, and satisfactory anatomical success, perineoplasty can be considered successful for treatment of the sensation of a wide vagina. Mustafa Ulubay, Ugur Keskin, Ulas Fidan, Mustafa Ozturk, Serkan Bodur, Ali Yılmaz, Mehmet Ferdi Kinci, and Mufit Cemal Yenen Copyright © 2016 Mustafa Ulubay et al. All rights reserved. Tomographic Ultrasound Imaging to Control the Placement of Tension-Free Transobturator Tape in Female Urinary Stress Incontinence Tue, 16 Aug 2016 16:08:01 +0000 Purpose. The objective was to evaluate, by means of tomographic ultrasound imaging (TUI), the reliability of a novel approach for determining the position of the implanted tension-free transobturator tape (TOT). Furthermore, we analyzed the association between the position of the tape at rest and the subjective cure in stress incontinent women. Methods. This retrospective pilot study consists of 32 stress incontinent women, who underwent TOT procedure and routine sonographic control at day 1 postoperatively and at follow-up visit. TUI was applied on the resulting 4D volumes, thereby delivering 9 axial slices with a 4 mm interslice distance starting at the meatus urethrae internus in caudal direction. The reliability of the approach was tested by two examiners. Postoperative and follow-up ultrasound parameters of uncured and cured patients were analyzed. Results. Measurements of the position of the TOT demonstrated high intraclass correlation coefficients. We found minor differences between sonographic parameters at day 1 postoperatively and at follow-up after a median period of 321 days. In cured patients, the position of the tape was measured in a more caudal position than in uncured patients. Conclusions. TUI can be a reliable method for determining the position of the tape. Further studies are needed to evaluate whether the postoperatively determined position can be used as an indicator of future subjective cure. Charlotte M. Gräf, Tomas Kupec, Elmar Stickeler, Tamme W. Goecke, Ivo Meinhold-Heerlein, and Laila Najjari Copyright © 2016 Charlotte M. Gräf et al. All rights reserved. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options Thu, 04 Aug 2016 08:25:20 +0000 Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes. Antonio Simone Laganà, Salvatore Giovanni Vitale, Maria Antonietta Trovato, Vittorio Italo Palmara, Agnese Maria Chiara Rapisarda, Roberta Granese, Emanuele Sturlese, Rosanna De Dominici, Stefano Alecci, Francesco Padula, Benito Chiofalo, Roberta Grasso, Pietro Cignini, Paolo D’Amico, and Onofrio Triolo Copyright © 2016 Antonio Simone Laganà et al. All rights reserved. Diagnostic Potential of Evaluation of SDF-1α and sRAGE Levels in Threatened Premature Labor Sun, 31 Jul 2016 07:02:40 +0000 Preterm birth remains the most prevalent cause of neonatal morbidity. This study aimed to evaluate the diagnostic value of SDF-1α, resistin, secretory RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) in preterm labor. A total of 211 pregnant women participated in the study. Group A contained 72 women between 22 and 36 weeks of gestation, with premature labor, who finally had preterm birth. Group B contained 66 women in labor between 37 and 41 weeks of gestation. Women in group A had lower SDF-1α and sRAGE levels than those in group B. Moreover, in group A, SDF-1α and sRAGE levels were correlated with the latency period from the occurrence of premature labor symptoms until delivery. Sensitivity and specificity of studied parameters for prediction of preterm birth were 95% and 40% for SDF-1α and 51.3% and 93.5% for sRAGE, respectively. The prognostic value of plasma SDF-1α and sRAGE levels was comparable with that of cervical length ultrasound measurement and serum C-reactive protein levels. We conclude that SDF-1α and sRAGE appear to play a major role in the diagnosis of preterm birth and its evaluation could be convenient and useful for predicting preterm birth. Rafał Rzepka, Barbara Dołęgowska, Aleksandra Rajewska, Daria Sałata, Marta Budkowska, Sebastian Kwiatkowski, and Andrzej Torbé Copyright © 2016 Rafał Rzepka et al. All rights reserved. Delivery after Operation for Deeply Infiltrating Endometriosis Tue, 19 Jul 2016 08:22:41 +0000 Background. It has been suggested that, during pregnancy, endometriosis can cause a variety of disease-related complications. Objectives. The purpose of the study was to find out if women with histologically confirmed endometriosis do have a higher risk of adverse pregnancy outcome and if they suffer from a higher rate of complications during labor. Study Design. 51 women who underwent surgery because of deeply infiltrating endometriosis in the General Hospital Linz and the Women’s General Hospital Linz and who gave birth in the Women’s General Hospital Linz after the surgery were included in our survey. Results. 31 women (60.8%) had a spontaneous delivery and in 20 women (39.2%) a caesarean section was performed. There were no cases of third- and fourth-degree perineal lacerations. Collectively there were 4 cases (7.8%) of preterm delivery and one case (2.0%) of premature rupture of membranes. In two women (6.5%) a retained placenta was diagnosed. Conclusions. Our study is the first description on delivery modes after surgery for deeply infiltrating endometriosis. We did not find an elevated risk for perineal or vaginal laceration in women with a history of surgery for deeply infiltrating endometriosis, even when a resection of the rectum or of the posterior vaginal wall had been performed. Christina Allerstorfer, Peter Oppelt, Simon H. Enzelsberger, Andreas Shamiyeh, Wolfgang Schimetta, Omar Josef Shebl, and Richard Bernhard Mayer Copyright © 2016 Christina Allerstorfer et al. All rights reserved. Subclinical Hypothyroidism in PCOS: Impact on Presentation, Insulin Resistance, and Cardiovascular Risk Tue, 12 Jul 2016 06:23:35 +0000 Aim of Study. To assess status of thyroid function and thyroid disorders particularly subclinical hypothyroidism (SCH) in subjects with polycystic ovarian syndrome (PCOS) and impact of SCH on various clinical and biochemical parameters and cardiovascular risk in PCOS. Methods. Hundred females diagnosed with PCOS as per Rotterdam criteria and 100 normal controls were recruited and were subjected to elaborate anthropometric, clinical, and biochemical assessment. Results. Notable findings included significantly higher frequency of subjects with subclinical hypothyroidism (), autoimmune thyroiditis (), and goitre () in polycystic ovarian syndrome subjects compared to control subjects. Further SCH PCOS subjects were found to harbor significantly higher HOMA-IR () and frequency of subjects with dyslipidemia () compared to both euthyroid PCOS and euthyroid control subjects. Though frequency of subjects with cardiovascular risk factors was higher in SCH PCOS group than euthyroid PCOS group, it failed to reach statistical significance. Conclusion. We concluded that PCOS is associated with high incidence of SCH and AIT compared to normal population and SCH poses increased risk of cardiovascular disorder in PCOS. Qun Yu and Jin-Bei Wang Copyright © 2016 Qun Yu and Jin-Bei Wang. All rights reserved. Feasibility and Safety of Absorbable Knotless Wound Closure Device in Laparoscopic Myomectomy Mon, 27 Jun 2016 14:13:41 +0000 Purpose. Myomectomy has been performed through laparoscopy. Suturing is known as rate-limiting step in laparoscopic myomectomy. The present study was aimed at comparing the clinical outcomes of absorbable knotless wound closure device with the results of conventional suturing. Methods. This prospective study included 62 women who underwent laparoscopic myomectomy at Taipei City Hospital, Zhongxiao Branch, from January 2010 through to August 2012. The patients were randomized into two groups according to suturing materials, the knotless group and the 2-0 Vicryl suture group. Patient demographics, overall operative time, and intraoperative blood loss were compared between two groups. Results. Demographic characteristics and laboratory variables before surgery were comparable. Operative time was significantly shorter in knotless group compared with that in 2-0 Vicryl suture group ( versus minutes; ). The results revealed a significant difference in intraoperative blood loss between two groups (knotless versus 2-0 Vicryl: versus ). Use of absorbable knotless wound closure device was associated with greater hemostasis compared with that of 2-0 Vicryl. During a 2-year follow-up period, 12 patients (46.2%) from the group with absorbable knotless wound closure device and 14 patients (38.9%) from 2-0 Vicryl suture group became pregnant. Conclusion. Closure of myometrium using absorbable knotless wound closure device after laparoscopic myomectomy resulted in a shorter operative time and less blood loss. Chying-Chyuan Chan and Ching-Yu Lee Copyright © 2016 Chying-Chyuan Chan and Ching-Yu Lee. All rights reserved. Total Laparoscopic Hysterectomy in Patients with Large Uteri: Comparison of Uterine Removal by Transvaginal and Uterine Morcellation Approaches Wed, 22 Jun 2016 06:02:15 +0000 The aim of this study was to compare the clinical results of total laparoscopic hysterectomy (TLH) for large uterus with uterus size of 12 gestational weeks (g.w.) or greater through transvaginal or uterine morcellation approaches. We retrospectively collected the clinical data of those undergoing total laparoscopic hysterectomies between January 2004 and June 2012. Intraoperative and postoperative outcomes were compared between patients whose large uterus was removed through transvaginal or morcellation approaches. The morcellation group has significantly shorter mean operation time and uterus removal time and smaller incidence of intraoperative complications than the transvaginal group (all ). No statistical significant difference regarding the mean blood loss, uterine weight, and length of hospital stay was noted in the morcellation and transvaginal groups (all ). In two groups, there was one patient in each group who underwent conversion to laparotomy due to huge uterus size. With regard to postoperative complications, there was no statistical significant difference regarding the frequencies of pelvic hematoma, vaginal stump infection, and lower limb venous thrombosis in two groups (all ). TLH through uterine morcellation can reduce the operation time, uterus removal time, and the intraoperative complications and provide comparable postoperative outcomes compared to that through the transvaginal approaches. Haibo Wang, Ping Li, Xiujuan Li, Licai Gao, Caihong Lu, Jinrong Zhao, and Ai-ling Zhou Copyright © 2016 Haibo Wang et al. All rights reserved. The Value of Contrast-Enhanced Ultrasound in the Diagnosis of Cesarean Scar Pregnancy Tue, 31 May 2016 07:52:04 +0000 Objective. To evaluate the value of contrast-enhanced ultrasound (CEUS) in the cesarean scar pregnancy (CSP). Methods. Clinical data from 92 patients with lower uterine segment pregnancy, who underwent conventional ultrasound and CEUS examination in the Department of Obstetrics and Gynecology, were collected by Xinqiao Hospital Third Military Medical University from March 2014 to March 2015. The parameters of ultrasound contrast time-intensity curve (TIC), including arrival time, time to peak, time from peak to one half, basic intensity, peak intensity, and wash-in slope, were analyzed. Results. Of the 92 cases of patients with pregnancy in the lower uterine segment, 52 cases were CSP, and 40 cases were intrauterine pregnancy. CEUS was significantly better than conventional ultrasound in terms of sensitivity, negative predictive value, Youden index, and diagnostic accuracy (). There was no significant difference in specificity and positive predictive value (). Conclusion. CEUS has a higher accuracy than conventional ultrasound in diagnosis of CSP. Xi Xiong, Ping Yan, Chunyan Gao, Qiulei Sun, and Fenglian Xu Copyright © 2016 Xi Xiong et al. All rights reserved. Preconception Care: A New Standard of Care within Maternal Health Services Sun, 29 May 2016 07:43:55 +0000 Emerging research suggests that much pediatric affliction has origins in the vulnerable phase of fetal development. Prenatal factors including deficiency of various nutrients and exposure to assorted toxicants are major etiological determinants of myriad obstetrical complications, pediatric chronic diseases, and perhaps some genetic mutations. With recent recognition that modifiable environmental determinants, rather than genetic predestination, are the etiological source of most chronic illness, modification of environmental factors prior to conception offers the possibility of precluding various mental and physical health conditions. Environmental and lifestyle modification through informed patient choice is possible but evidence confirms that, with little to no training in clinical nutrition, toxicology, or environmental exposures, most clinicians are ill-equipped to counsel patients about this important area. With the totality of available scientific evidence that now exists on the potential to modify disease-causing gestational determinants, failure to take necessary precautionary action may render members of the medical community collectively and individually culpable for preventable illness in children. We advocate for environmental health education of maternity health professionals and the widespread adoption and implementation of preconception care. This will necessitate the translation of emerging knowledge from recent research literature, to health professionals, to reproductive-aged women, and to society at large. Stephen J. Genuis and Rebecca A. Genuis Copyright © 2016 Stephen J. Genuis and Rebecca A. Genuis. All rights reserved. Decreased Cytotoxicity of Peripheral and Peritoneal Natural Killer Cell in Endometriosis Thu, 12 May 2016 13:12:16 +0000 Endometriosis causes significant chronic pelvic pain, dysmenorrhea, and infertility and affects 10% of all women. In endometriosis, ectopic endometrium surviving after retrograde menstruation exhibits an abnormal immune response characterized by increased levels of activated macrophages and inflammatory cytokines. Particularly, dysfunctional natural killer (NK) cells play an important role in the pathogenesis of the disease by either facilitating or inhibiting the survival, implantation, and proliferation of endometrial cells. NK cells in the peritoneum and peritoneal fluid exhibit reduced levels of cytotoxicity in women with endometriosis. Several cytokines and inhibitory factors in the serum and peritoneal fluid also dysregulate NK cell cytotoxicity. Additionally, increased numbers of immature peripheral NK cells and induction of NK cell apoptosis are evident in the peritoneal fluid of women with endometriosis. The high rate of endometriosis recurrence after pharmaceutical or surgical treatment, which is associated with dysfunctional NK cells, indicates that new immunomodulatory management strategies are required. A good understanding of immune dysfunction would enable improvement of current treatments for endometriosis. InCheul Jeung, Keunyoung Cheon, and Mee-Ran Kim Copyright © 2016 InCheul Jeung et al. All rights reserved. Demographic and Clinical Features of Endometrial Polyps in Patients with Endometriosis Tue, 03 May 2016 09:18:01 +0000 Aims. To compare the clinical features of endometrial polyps (EPs) between patients with endometriosis (EM) (EM group) and without EM (non-EM group). Methods and Results. Seventy-six cases in the EM group and 133 cases in the non-EM group underwent laparotomy or hysteroscopy and laparoscopy; later, it was confirmed that the results by pathology from July 2002 to April 2008 in the Department of Gynecology and Obstetrics at the First Affiliated Hospital of Sun Yat-sen University. The recurrence of EPs was followed up after the surgery until 2013. The following parameters were assessed: age, gravidity, parity, infertility, and menstrual cycle changes, as well as polyps diameters, locations, number, association with the revised American Fertility Society (r-AFS) classification, and their recurrence. On review, 76 EPs cases of EM group histologically resembled EPs but the majority of EPs with EM occurred in primary infertility cases and in fewer pregnancy rate women who had stable and smaller EPs without association with the AFS stage. The recurrence rate of EPs in EM group was higher than that in non-EM group. Conclusion. It is important to identify whether infertile patients with EM are also having EPs. Removing any coexisting EPs via hysteroscopy would be clinically helpful in treating endometriosis-related infertility in these patients. Ningning Wang, Yufeng Zhang, and Bin Liu Copyright © 2016 Ningning Wang et al. All rights reserved. Biomechanical, Topological and Chemical Features That Influence the Implant Success of an Urogynecological Mesh: A Review Thu, 28 Apr 2016 11:36:39 +0000 Synthetic meshes are normally used to treat several diseases in the field of urogynecological surgery. Not-optimal selection of mesh and/or its not-correct implant may increase patient’s pain and discomfort. The knowledge of mechanical behaviour and topological and chemical properties of a mesh plays a fundamental role to minimize patient’s suffering and maximize the implant success. We analysed several papers reporting the meshes application for urogynecological pathologies, to extrapolate the principal parameters that normally are used to characterise the biomechanical, topological, and chemical properties, and to verify their influence on implant success. In this way we want demonstrate that, knowing these features, it is possible to foresee the success of a mesh implant. This review shows that the application of a mesh strictly depends on elastic modulus, failure load, porosity and pore size, filament diameter, polymer weight, and crystallinity. To increase the success of the implant and to help choice of optimal mesh for a clinical need, two indexes have been proposed for comparing, in an easier way, the mechanical performance of different commercially available meshes. Carmelo De Maria, Vito Santoro, and Giovanni Vozzi Copyright © 2016 Carmelo De Maria et al. All rights reserved. The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis Sun, 17 Apr 2016 10:43:06 +0000 Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation. Petra Pateisky, Dietmar Pils, Lorenz Kuessel, Ladislaus Szabo, Katharina Walch, Reinhard Obwegeser, René Wenzl, and Iveta Yotova Copyright © 2016 Petra Pateisky et al. All rights reserved. Are Patients with Polycystic Ovarian Syndrome Ideal Candidates for Oocyte Donation? Tue, 12 Apr 2016 14:21:53 +0000 Background. The use of donated oocytes for in vitro fertilization treatment in patients with ovarian failure is universally recognized. But would patients with polycystic ovarian syndrome (PCOS) be a good choice for egg donation programs? Objective. Comparing the pregnancy rates of egg receptors from donor patients diagnosed with PCOS to receptors from donors without PCOS. Design. Retrospective cohort study. Methods. A total of 234 patients who had undergone egg reception program were separated into two groups: Group I, receptors from PCOS donors (); Group II, receptors from donors without PCOS (). Medical records were reviewed and the fertilization, implantation, and pregnancy rates were calculated. Results. PCOS patients had an average of 3.23 more oocytes retrieved, but there were no differences in the number of mature oocytes that were used for donation between the groups. We also observed that the number of transferred embryos was also not significantly different, as well as the fertilization and implantation rates. The clinical pregnancy rates were not significantly different: 28% and 26% in Group I and Group II, respectively. Conclusions. Women with PCOS should not be excluded from egg donation programs. George Queiroz Vaz, Alessandra Viviane Evangelista, Cassio Alessandro Paganoti Sartorio, Maria Cecilia Almeida Cardoso, Maria Cecilia Erthal, Paulo Gallo, and Marco Aurelio Pinho Oliveira Copyright © 2016 George Queiroz Vaz et al. All rights reserved. Epidemiology of Endometriosis in France: A Large, Nation-Wide Study Based on Hospital Discharge Data Mon, 11 Apr 2016 16:03:14 +0000 We aimed to assess the prevalence of hospitalization for endometriosis in the general population in France and in each French region and to describe temporal trends, rehospitalization rates, and prevalence of the different types of endometriosis. The analyses were carried out on French hospital discharge data and covered the period 2008–2012 and a population of 14,239,197 women of childbearing age. In this population, the prevalence of hospitalization for endometriosis was 0.9%, ranging from 0.4% to 1.6% between regions. Endometriosis affected 1.5% of hospitalized women of childbearing age, ranging from 1.0% to 2.4% between regions. The number of patients hospitalized for endometriosis significantly increased over the study period (). Of these, 4.2% were rehospitalized at least once at one year: ranging from 2.7% to 6.3% between regions. The cumulative rehospitalization rate at 3 years was 6.9%. The types of endometriosis according to the procedures performed were as follows: ovarian (40–50%), peritoneal (20–30%), intestinal (10–20%), and ureteral or bladder (<10%), with significant differences between regions. This is the first detailed epidemiological study of endometriosis in France. Further studies are needed to assess the reasons for the increasing prevalence of endometriosis and for the significant differences in regional prevalence of this disease. Peter von Theobald, Jonathan Cottenet, Silvia Iacobelli, and Catherine Quantin Copyright © 2016 Peter von Theobald et al. All rights reserved. Different Levels of DNA Methylation Detected in Human Sperms after Morphological Selection Using High Magnification Microscopy Mon, 11 Apr 2016 09:39:21 +0000 Objective. To analyze DNA methylation levels between two groups of spermatozoa taken from the same sample, following morphological selection by high magnification (HM) at 6100x microscopy. A prospective study was conducted and studied 876 spermatozoa from 10 randomly selected men. Sperm morphology was characterized at HM according to criteria previously established. High-scoring Score 6 and low-scoring Score 0 sperm were selected. Sperm DNA methylation level was assessed using an immunoassay method targeting 5-methylcytosine residues by fluorescence microscopy with imaging analysis system to detect DNA methylation in single spermatozoon. Results. In total, 448 S6 spermatozoa and 428 S0 spermatozoa were analyzed. A strong relationship was found between sperm DNA methylation levels and sperm morphology observed at HM. Sperm DNA methylation level in the S6 group was significantly lower compared with that in the S0 group (), OR = 2.4; and , as determined using the Wilcoxon test. Conclusion. Differences in DNA methylation levels are associated with sperm morphology variations as observed at HM, which allows spermatozoa with abnormal levels to be discarded and ultimately decrease birth defects, malformations, and epigenetic diseases that may be transmitted from sperm to offspring in ICSI. Nino Guy Cassuto, Debbie Montjean, Jean-Pierre Siffroi, Dominique Bouret, Flora Marzouk, Henri Copin, and Moncef Benkhalifa Copyright © 2016 Nino Guy Cassuto et al. All rights reserved. Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina Tue, 05 Apr 2016 14:16:12 +0000 Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230–240 g, ) were divided into three groups and subjected to a sham operation (control group, ), bilateral ovariectomy (Ovx group, ), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, ). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication. Kyung-Jin Oh, Hyun-Suk Lee, Kyuyoun Ahn, and Kwangsung Park Copyright © 2016 Kyung-Jin Oh et al. All rights reserved. Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much? Wed, 30 Mar 2016 06:38:20 +0000 Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries. Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed. Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63–0.86, ) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy. Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients. Safak Olgan, Sezcan Mumusoglu, and Gurkan Bozdag Copyright © 2016 Safak Olgan et al. All rights reserved. An Advanced Orthotopic Ovarian Cancer Model in Mice for Therapeutic Trials Wed, 23 Mar 2016 14:33:44 +0000 A nude mouse received subcutaneous injection of human ovarian cancer cells HO-8910PM to form a tumor, and then the tumor fragment was surgically transplanted to the ovary of a recipient mouse to establish an orthotopic cancer model. Tumors occurred in 100% of animals. A mouse displayed an ovarian mass, ascites, intraperitoneal spread, and lung metastasis at natural death. The mean survival time was days, with median survival time of 28.5 days. The findings indicated that the present mouse model can reflect the biological behavior of advanced human ovarian cancers. This in vivo model can be used to explore therapeutic means against chemoresistance and metastasis, and an effective treatment would prolong the survival time. Ying Zhang, Li Luo, Xueling Zheng, and Tinghe Yu Copyright © 2016 Ying Zhang et al. All rights reserved. Efficacy of Combined Laparoscopic and Hysteroscopic Repair of Post-Cesarean Section Uterine Diverticulum: A Retrospective Analysis Tue, 15 Mar 2016 16:28:31 +0000 Background. Diverticulum, one of the long-term sequelae of cesarean section, can cause abnormal uterine bleeding and increase the risk of uterine scar rupture. In this study, we aimed to evaluate the efficacy of combined laparoscopic and hysteroscopic repair, a newly occurring method, treating post-cesarean section uterine scar diverticulum. Methods. Data relating to 40 patients with post-cesarean section uterine diverticulum who underwent combined laparoscopic and hysteroscopic repair were retrospectively analyzed. Preoperative clinical manifestations, size of uterine defects, thickness of the lower uterine segment (LUS), and duration of menstruation were compared with follow-up findings at 1, 3, and 6 months after surgery. Results. The average preoperative length and width of uterine diverticula and thickness of the lower uterine segment were recorded and analyzed. The average durations of menstruations at 1, 3, and 6 months after surgery were significantly shorter than the preoperative one (), respectively. At 6 months after surgery, the overall success improvement rate of surgery was 90% (36/40). Three patients (3/40 = 7.5%) developed partial improvement, and 1/40 (2.5%) was lost to follow-up. Conclusions. Our findings showed that combined treatment with laparoscopy and hysteroscopy was an effective method for the repair of post-cesarean section uterine diverticulum. Cuilan Li, Shiyan Tang, Xingcheng Gao, Wanping Lin, Dong Han, Jinguo Zhai, Xuetang Mo, and Lee Jaden Gil Yu Kang Zhou Copyright © 2016 Cuilan Li et al. All rights reserved. Periostin Facilitates the Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells through ILK-Akt Signaling Pathway Sun, 13 Mar 2016 10:13:00 +0000 Although periostin was confirmed to facilitate the pathogenesis of endometriosis by enhancing the migration, invasion, and adhesion of human endometrial stromal cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still unknown. The current study aimed to determine whether periostin enhanced the epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women with endometriosis. The migration and invasion abilities of EECs were evaluated by transwell assays. Expressions of proteins were detected by western blot. After treatment with periostin, the migration and invasion abilities of EECs were enhanced. Additionally, E-cadherin and keratin were downregulated while N-cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p-Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were downregulated while E-cadherin and keratin were upregulated. Although periostin weakened the above effects in EECs after silencing the expression of ILK, it failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin may be a new clinical therapy target for endometriosis. Qiao-mei Zheng, Jing-jing Lu, Jing Zhao, Xuan Wei, Lu Wang, and Pei-shu Liu Copyright © 2016 Qiao-mei Zheng et al. All rights reserved. Cohort Records Study of 19,655 Women Who Received Postabortion Care in a Tertiary Hospital 2010–2013 in China: What Trends Can Be Observed? Thu, 18 Feb 2016 11:32:04 +0000 The retrospective cohort epidemiological study was to investigate the characteristics of women who underwent induced abortion. Data were retrospectively collected from women who underwent induced abortions () at the Xiamen Maternity and Child Health Care Hospital (2010–2013). The characteristics of women who underwent induced abortions included mean age, unmarried status, no previous deliveries, first pregnancy, ≥2 abortions including the current one, and a history of caesarian section. From 2010 to 2013, mean age increased and declines were observed in the ratio of induced abortions to live births, the proportion of induced abortions among women of 15–24 years, those who were unmarried, had their first pregnancy, or had no history of delivery. However, the rates of induced abortions increased among women who were lactating, had a history of caesarian section, or had an interpregnancy interval of <6 months. This snapshot of induced abortions in China might suggest that the numbers are increasing but the ratio to live births has fallen. Methods should be improved to prevent unwanted pregnancies and reduce the number of induced abortions in China. It must be emphasized that differences in mentality and culture between countries might limit the representativeness of these results. Zhen-Yu Luo, Song Quan, Dong-Ning Chai, and Wei-Hong Zhang Copyright © 2016 Zhen-Yu Luo et al. All rights reserved. TOT 8/4: A Way to Standardize the Surgical Procedure of a Transobturator Tape Mon, 15 Feb 2016 13:19:52 +0000 Suburethral tapes are placed “tension-free” below the urethra. Several studies reported considerable differences of the distance between urethra and tape. These distances ranged from 1 to 10 mm amongst different patients. This either caused urethral obstruction or had no effect on urinary incontinence. Therefore, we decided to standardize the procedure by placing a Hegar dilator of 8-millimeter diameter in the urethra and another Hegar dilator of 4-millimeter diameter between the urethra and the tape during transobturator tape placement. Using that simple technique, which we named “TOT 8/4,” we observed that 83% of the tapes were placed in the desired distance between 3 and 5 millimeters below the urethra. Sebastian Ludwig, Martin Stumm, Peter Mallmann, and Wolfram Jager Copyright © 2016 Sebastian Ludwig et al. All rights reserved. Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis Sun, 14 Feb 2016 13:46:11 +0000 The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms. Yu Li, Hong Ma, Ye Lu, B. J. Tan, L. Xu, Temitope O. Lawal, Gail B. Mahady, and Daniel Liu Copyright © 2016 Yu Li et al. All rights reserved. Downregulation of Mitofusin 2 in Placenta Is Related to Preeclampsia Sun, 31 Jan 2016 09:17:37 +0000 Background. Mitofusin 2 (Mfn2) is a novel mitochondrial protein that is implicated in cellular proliferation and metabolism; however, the role of Mfn2 in preeclampsia (PE) remains unknown. This study aimed to explore the relationship between Mfn2 and PE. Method. Preeclamptic and normal pregnancies were enrolled in a comparative study. The expression of Mfn2 in placenta was detected by qRT-PCR. And the mitochondrial function was detected by ATP assay. Then TEV-1 cells were cultured in hypoxic conditions. mRNA and protein expressions of Mfn2 were detected by qRT-PCR and western blot separately. Cells’ viability was detected by MTT. And the mitochondrial function was detected by ATP and mitochondrial membrane potential (MMP) assay. We further knocked down the Mfn2 gene in TEV-1 cells and evaluated the cells’ viability. Results. Mfn2 and ATP expressions were significantly decreased in preeclamptic placentae compared to normal placentae. Mfn2 expression level and the viability of TEV-1 cells were reduced during hypoxic conditions. TEV-1 cells’ viability, ATP, and MMP levels were also significantly decreased after knockdown of the Mfn2 gene. Conclusions. These results suggest that defects in Mfn2 could cause mitochondrial dysfunction and decrease trophoblastic cells’ viability. Therefore, Mfn2 may be functionally involved in the pathogenesis of PE. Jun Yu, Xijiao Guo, Ruibao Chen, and Ling Feng Copyright © 2016 Jun Yu et al. All rights reserved. Use of Modified Polysaccharide 4DryField PH for Adhesion Prevention and Hemostasis in Gynecological Surgery: A Two-Center Observational Study by Second-Look Laparoscopy Sun, 24 Jan 2016 12:07:38 +0000 Purpose. This study evaluates both scopes of 4DryField PH, certified for adhesion prevention and hemostasis, in patients undergoing surgery for various and severe gynecological disorders. Methods. This is a two-institutional study. Adhesion prevention efficacy was evaluated using video documentation of first-look laparoscopies (FLL) and second-look laparoscopies (SLL); other patient data were analyzed retrospectively. Twenty patients with various disorders were evaluated, 4 assigned to a uterus pathology, 10 to endometriosis, and 6 to an adhesion disease group. Nine patients received 4DryField primarily for hemostasis and 11 solely for adhesion prevention. Nineteen patients had SLL after 5 to 12 weeks and one after 13 months. Results. At FLL with 4DryField, immediate hemostasis could be achieved in diffuse bleeding. At SLL, effective adhesion prevention was observed in 18 of all 20 women, with only 2 revealing major adhesions. In particular, only 1 of the 6 women with adhesion disease as predominant disorder showed major adhesions at SLL. Conclusions. Modified polysaccharide 4DryField is not only effective in diffuse bleeding. In this cohort with extensive surgery for various gynecological pathologies, 4DryField showed effective adhesion prevention as confirmed at SLL, too. Its use as premixed gel is a convenient variant for treatment of large peritoneal wounds. Matthias Korell, Nicole Ziegler, and Rudy Leon De Wilde Copyright © 2016 Matthias Korell et al. All rights reserved. Activity of Proteolytic Enzymes and Level of Cystatin C in the Peripartum Period Wed, 20 Jan 2016 09:46:47 +0000 Objectives. The aim of the study was to evaluate the activity of cathepsin B, collagenases, trypsin, and plasmin and concentration of cystatin C in serum of healthy pregnant women in peripartum period. Study Design. The study group included 45 women in uncomplicated pregnancies. Blood samples were collected in four time points. Enzyme activity was measured by spectrofluorometric method. The level of cystatin C was measured using immunonephelometric method. Results. Mean activity of cathepsin B and the level of serum cystatin C were significantly higher in the study group. Collagenase activity was significantly lower in the study group than the control group. No differences in collagenase, plasmin, and trypsin activity on each day of the peripartum period were found. Conclusion. High activity of cathepsin B and increased level of cystatin C are typical for women in late pregnancy. Those levels significantly decrease after delivery which can be associated with potential role of those markers in placental separation. The insignificant changes of cystatin C level in the peripartum period seem to exclude the possibility of using cystatin C as a marker for renal insufficiency in the peripartum period but additional research is necessary to investigate the matter further. Anna Cyganek, Aleksandra Wyczalkowska-Tomasik, Patrycja Jarmuzek, Barbara Grzechocinska, Zoulikha Jabiry-Zieniewicz, Leszek Paczek, and Miroslaw Wielgos Copyright © 2016 Anna Cyganek et al. All rights reserved. The Prognosis of IVF in Poor Responders Depending on the Bologna Criteria: A Large Sample Retrospective Study from China Wed, 30 Dec 2015 08:51:03 +0000 Objective. To analyze the treatment outcomes of patients who accepted IVF/ICSI-ET, diagnosed POR according to Bologna criteria. Study Design. Retrospective cohort study of one reproductive medical center, from 1st Jan., 2009, to 31st Dec., 2014. All patients fulfilled the Bologna criteria and accept IVF/ICSI-ET treatment with stimulation cycle. The main outcome measures were clinical pregnancy rate (CPR) and live birth rate (LBR). Results. There were 5770 eligible cycles included in this study. The incidence of POR was 10.3% (6286/62194). The overall CPR was 18.7%, IR was 11.6%, LBR/ET was 11.5%, and LBR/OPU was 8.3%. The cycle cancellation for no available oocyte or embryo was 4.9% and 18.6%, respectively. The subgroup of younger POR patients got highest CPR and LBR/ET, which decreased while increasing maternal age. Within three attempts, the patients got similar CPR and LBR. Conclusion. In conclusion, our study supports the Bologna criteria that defined women with poor IVF outcomes. But those younger than 42 years old with the first 3 attempts of IVF could got acceptable CPR and LBR. Shuo Yang, Xinna Chen, Xiumei Zhen, Haiyan Wang, Caihong Ma, Rong Li, Ping Liu, and Jie Qiao Copyright © 2015 Shuo Yang et al. All rights reserved. Oxidative Stress in Placenta: Health and Diseases Sun, 29 Nov 2015 11:59:06 +0000 During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. Fan Wu, Fu-Ju Tian, and Yi Lin Copyright © 2015 Fan Wu et al. All rights reserved. Clinical Outcomes and Urodynamic Effects of Tailored Transvaginal Mesh Surgery for Pelvic Organ Prolapse Sun, 08 Nov 2015 06:46:19 +0000 Objective. To evaluate the clinical outcomes and urodynamic effects of tailored anterior transvaginal mesh surgery (ATVM) and tailored posterior transvaginal mesh surgery (PTVM). Methods. We developed ATVM for the simultaneous correction of cystocele and stress urinary incontinence and PTVM for the simultaneous correction of enterocoele, uterine prolapse, vaginal stump prolapse, and rectocele. Results. A total of 104 women enrolled. The median postsurgical follow-up was 25.5 months. The anatomic cure rate was 98.1% (102/104). Fifty-eight patients underwent urodynamic studies before and after surgeries. The pad weight decreased from 29.3 ± 43.1 to 6.4 ± 20.9 g at 3 months. Among the 20 patients with ATVM, 13 patients had objective stress urinary incontinence (SUI) at baseline while 8 patients came to have no demonstrated SUI (NDSUI), and 2 improved after surgery. Among the 38 patients who underwent ATVM and PTVM, 24 had objective SUI at baseline while 18 came to have NDSUI, and 2 improved after surgery. Mesh extrusion (n = 4), vaginal hematoma (n = 3), and voiding difficulty (n = 2) were noted postoperatively. Quality of life was substantially improved. Conclusions. Our findings document the advantages of these two novel pelvic reconstructive surgeries for pelvic organ prolapse, which had a positive impact on quality of life. ATVM surgery additionally provided an anti-incontinence effect. This clinical trial is registered at (NCT02178735). Ting-Chen Chang, Sheng-Mou Hsiao, Chi-Hau Chen, Wen-Yih Wu, and Ho-Hsiung Lin Copyright © 2015 Ting-Chen Chang et al. All rights reserved. Comment on “The Role of Overweight and Obesity in In Vitro Fertilization Outcomes of Poor Ovarian Responders” Mon, 05 Oct 2015 07:32:37 +0000 Raoul Orvieto Copyright © 2015 Raoul Orvieto. All rights reserved. The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life Sun, 30 Aug 2015 14:19:54 +0000 Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life. Giovanni Grandi, Angela Toss, Laura Cortesi, Laura Botticelli, Annibale Volpe, and Angelo Cagnacci Copyright © 2015 Giovanni Grandi et al. All rights reserved. Preterm Birth: Pathophysiology, Prevention, Diagnosis, and Treatment Sun, 30 Aug 2015 08:00:33 +0000 Igor Hudić, Babill Stray-Pedersen, and Vajdana Tomić Copyright © 2015 Igor Hudić et al. All rights reserved. The Effect of Omega-3 Docosahexaenoic Acid Supplementation on Gestational Length: Randomized Trial of Supplementation Compared to Nutrition Education for Increasing n-3 Intake from Foods Thu, 27 Aug 2015 12:40:35 +0000 Objective. DHA supplementation was compared to nutrition education to increase DHA consumption from fish and DHA fortified foods. Design. This two-part intervention included a randomized double-blind placebo controlled DHA supplementation arm and a nutrition education arm designed to increase intake of DHA from dietary sources by 300 mg per day. Setting. Denver Health Hospitals and Clinics, Denver, Colorado, USA. Population. 871 pregnant women aged 18–40 were recruited between16 and 20 weeks of gestation of whom 564 completed the study and complete delivery data was available in 505 women and infants. Methods. Subjects received either 300 or 600 mg DHA or olive oil placebo or nutrition education. Main Outcome Variable. Gestational length. Results. Gestational length was significantly increased by 4.0–4.5 days in women supplemented with 600 mg DHA per day or provided with nutrition education. Each 1% increase in RBC DHA at delivery was associated with a 1.6-day increase in gestational length. No significant effects on birth weight, birth length, or head circumference were demonstrated. The rate of early preterm birth (1.7%) in those supplemented with DHA (combined 300 and 600 mg/day) was significantly lower than in controls. Conclusion. Nutrition education or supplementation with DHA can be effective in increasing gestational length. Mary A. Harris, Melanie S. Reece, James A. McGregor, John W. Wilson, Shannon M. Burke, Marsha Wheeler, Jennifer E. Anderson, Garry W. Auld, Janice I. French, and Kenneth G. D. Allen Copyright © 2015 Mary A. Harris et al. All rights reserved. Psychobiobehavioral Model for Preterm Birth in Pregnant Women in Low- and Middle-Income Countries Thu, 27 Aug 2015 12:17:18 +0000 Preterm birth (PTB) is a final common outcome resulting from many interrelated etiological pathways; of particular interest is antenatal psychosocial distress (i.e., stress, anxiety, and depression). In LMI countries, both exposure to severe life stressors and rate of PTB are on average greater when compared with high-income countries. In LMI countries women are exposed to some of the most extreme psychosocial stress worldwide (e.g., absolute poverty, limited social resources). High prevalence of antenatal stress and depression have been observed in some studies from LMI countries. We propose a psychosocial, biological, and behavioral model for investigating the complex multisystem interactions in stress responses leading to PTB and explain the basis of this approach. We discuss ethical considerations for a psychosocial, biological, and behavioral screening tool to predict PTB from a LMI country perspective. Shahirose S. Premji, Ilona S. Yim, Aliyah Dosani (Mawji), Zeenatkhanu Kanji, Salima Sulaiman, Joseph W. Musana, Pauline Samia, Kiran Shaikh, Nicole Letourneau, and MiGHT Group Copyright © 2015 Shahirose S. Premji et al. All rights reserved. Preterm Birth: A Prominent Risk Factor for Low Apgar Scores Thu, 27 Aug 2015 11:49:43 +0000 Objective. To determine predictive risk factors for Apgar scores < 7 at 5 minutes at two hospitals providing tertiary care and secondary care, respectively. Methods. A retrospective registry cohort study of 21126 births (2006–2010) using data from digital medical records. Risk factors were analyzed by logistic regression analyses. Results.   was multivariately associated with the following: preterm birth; gestational week 32 + 0–36 + 6, (95% CI 2.9–5.3); week 28 + 0–31 + 6, (5–12); week < 28 + 0, (8–29); postterm birth, (1.7–2.3); multiple pregnancy, (1.79–6.96); previous cesarean section, (2.31–5.81); BMI 25–29, (1.09–1.55);    (1.20–2.41); nonnormal CTG at admission, (1.48–2.66). ≥1-para was associated with a decreased risk for , (0.25–0.47). In the univariate logistic regression analysis was associated with tertiary level care, (1.17–1.87); however, in the multivariate analysis there was no significant difference. Conclusion. A number of partially preventable risk factors were identified, preterm birth being the most evident. Further, no significant difference between the two hospital levels regarding the risk for low Apgar scores was detected. Maria Svenvik, Lars Brudin, and Marie Blomberg Copyright © 2015 Maria Svenvik et al. All rights reserved. Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes Thu, 27 Aug 2015 11:35:52 +0000 The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A) threatened premature labor (), (B) preterm premature rupture of membranes (), and (C) preterm rupture of membranes at term (). The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGE’s concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time ( = 0,422; = 0,001; = 0,413, = 0,004, resp.). High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, 0,05). The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction. Rafał Rzepka, Barbara Dołegowska, Aleksandra Rajewska, Sebastian Kwiatkowski, Daria Sałata, Marta Budkowska, Leszek Domański, Wioletta Mikołajek-Bedner, and Andrzej Torbé Copyright © 2015 Rafał Rzepka et al. All rights reserved. Increase in Preterm Birth during Demographic Transition in Chile from 1991 to 2012 Thu, 27 Aug 2015 09:46:19 +0000 Introduction. Universally mothers at 35 years or more have had higher maternal and perinatal risks. This study analyzed the trend of this group in maternal population and determined their risk of having premature children, during the demographic transition period in Chile. Materials and Methods. Epidemiological study conducted in the population of simple live births registered in the Chilean National Database Births of 1991–2012. Analyses were performed in three categories of maternal age: 35 or more, under 35, and 20 to 29 years. The risk of prematurity was measured by crude and Adjusted Odds Ratio from logistic regression model. Results. Mothers aged 35 and older increased in population from 10.6% in 1991 to 16.7% in 2012 and presented an overall prevalence of preterm delivery of 6.7%, higher prevalence than 20–29 age group (4.7%). In aging mothers, the Odds Ratio for preterm birth adjusted for education, marital status, and parity was 1.68 (95% CI (1.66–1.70)) compared to mothers aged 20–29. All differences were significant (). Conclusions. During Chilean demographic transition, mothers aged 35 or older increased steadily and significantly maintaining higher risks of preterm births. Policies to prevent and monitor the late motherhood could contribute to stopping the current trend. Paulina López Orellana Copyright © 2015 Paulina López Orellana. All rights reserved. Adjunctive Pessary Therapy after Emergency Cervical Cerclage for Cervical Insufficiency with Protruding Fetal Membranes in the Second Trimester of Pregnancy: A Novel Modification of Treatment Thu, 27 Aug 2015 09:16:57 +0000 Aim. To evaluate the effectiveness of adjunctive pessary therapy after emergency cervical cerclage (ECC) in improving perinatal outcome in cervical insufficiency with fetal membranes protruding into the vagina. Material and Methods. A retrospective analysis of patients treated at the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, between 2008 and 2013. The study group consisted of 15 women treated with ECC and a pessary and the control group consisted of 17 patients treated with cerclage only. Results. The mean gestational age at delivery was significantly higher in the study group (34.7 versus 29.7 weeks, ). The period between cerclage insertion and delivery was significantly longer in the study group (82.9 versus 52.1 days, ). The mean neonatal birthweight and neonatal “discharge alive” ratio were higher in the study group, although not statistically significant (2550 g versus 1883 g, , and 93.3% versus 70.5%, , resp.). NICU hospitalization rates were comparable (33.3% versus 35.3%, ). Conclusions. Adjunctive pessary therapy allows delaying delivery in women treated with ECC due to cervical insufficiency with protruding fetal membranes. It also seems to improve neonatal outcome, although the differences are not statistically significant. Further prospective study is required to prove these findings. Katarzyna Kosinska-Kaczynska, Dorota Bomba-Opon, Aleksandra Zygula, Bartosz Kaczynski, Piotr Wegrzyn, and Miroslaw Wielgos Copyright © 2015 Katarzyna Kosinska-Kaczynska et al. All rights reserved. Aberrant Gene Regulation in Obstetric, Gynecologic, and Reproductive Diseases Sun, 23 Aug 2015 12:41:48 +0000 Shi-Wen Jiang, Brian Brost, Dan Zhang, and Chun-E Ren Copyright © 2015 Shi-Wen Jiang et al. All rights reserved. Systematic Analysis of Endometrial Cancer-Associated Hub Proteins Based on Text Mining Sun, 23 Aug 2015 12:10:59 +0000 Objective. The aim of this study was to systematically characterize the expression of endometrial cancer- (EC-) associated genes and to analysis the functions, pathways, and networks of EC-associated hub proteins. Methods. Gene data for EC were extracted from the PubMed (MEDLINE) database using text mining based on NLP. PPI networks and pathways were integrated and obtained from the KEGG and other databases. Proteins that interacted with at least 10 other proteins were identified as the hub proteins of the EC-related genes network. Results. A total of 489 genes were identified as EC-related with , and 32 pathways were identified as significant (, ). A network of EC-related proteins that included 271 interactions was constructed. The 17 proteins that interact with 10 or more other proteins (, ) were identified as the hub proteins of this PPI network of EC-related genes. These 17 proteins are EGFR, MET, PDGFRB, CCND1, JUN, FGFR2, MYC, PIK3CA, PIK3R1, PIK3R2, KRAS, MAPK3, CTNNB1, RELA, JAK2, AKT1, and AKT2. Conclusion. Our data may help to reveal the molecular mechanisms of EC development and provide implications for targeted therapy for EC. However, corrections between certain proteins and EC continue to require additional exploration. Huiqiao Gao and Zhenyu Zhang Copyright © 2015 Huiqiao Gao and Zhenyu Zhang. All rights reserved. Participation of WNT and β-Catenin in Physiological and Pathological Endometrial Changes: Association with Angiogenesis Thu, 20 Aug 2015 11:25:50 +0000 WNT proteins are involved in embryonic development, sex determination, stem cell recruitment, angiogenesis, and cancer. They take part in morphological changes in the endometrium during development, regulate processes of endometrial proliferation and differentiation. This review presents current knowledge about implication of WNT proteins and β-catenin in physiological endometrial functions as well as their involvement in uterine carcinogenesis. Influence of WNT proteins on the formation of blood vessel, taking place both under healthy and pathological conditions, is also considered. Participation of WNT proteins, β-catenin, and inhibitors and inducers of WNT signaling in the process of endometrial angiogenesis is largely unknown. Thus, confirmation of their local and systemic participation in the process of endometrial angiogenesis may in the long term help to establish new diagnostic and therapeutic approaches in conditions associated with the pathology of the female reproductive system. Jolanta Kiewisz, Tomasz Wasniewski, and Zbigniew Kmiec Copyright © 2015 Jolanta Kiewisz et al. All rights reserved. Profiling of Selected MicroRNAs in Proliferative Eutopic Endometrium of Women with Ovarian Endometriosis Thu, 20 Aug 2015 08:49:47 +0000 It has been well documented that aberrant expression of selected microRNAs (miRNAs) might contribute to the pathogenesis of disease. The aim of the present study is to compare miRNA expression by the most comprehensive locked-nucleic acid (LNA) miRNA microarray in eutopic endometrium of patients with endometriosis and control. In the study we recruited 21 patients with endometriosis and 25 were disease-free women. The miRNA expression profiles were determined using the LNA miRNA microarray and validated for selected molecules by real-time PCR. We identified 1198 human miRNAs significantly differentially altered in endometriosis versus control samples using false discovery rate of <5%. However only 136 miRNAs showed differential regulation by fold change of at least 1.3. By the use of selected statistical analysis we obtained 45 potential pathways that might play a role in the pathogenesis of endometriosis. We also found that natural killer cell mediated cytotoxicity pathway was found to be inhibited which is consistent with previous studies. There are several pathways that may be potentially dysregulated, due to abnormal miRNA expression, in eutopic endometrium of patients with endometriosis and in this way contribute to its pathogenesis. P. Laudanski, R. Charkiewicz, A. Tolwinska, J. Szamatowicz, A. Charkiewicz, and J. Niklinski Copyright © 2015 P. Laudanski et al. All rights reserved. Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells Thu, 20 Aug 2015 08:35:04 +0000 Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas-L, and the enzyme activity of caspase-3 (); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels. Yanxia Sui, Ya Yang, Ji Wang, Yi Li, Hongbing Ma, Hui Cai, Xiaoping Liu, Yong Zhang, Shufeng Wang, Zongfang Li, Xiaozhi Zhang, Jiansheng Wang, Rui Liu, Yanli Yan, Chaofan Xue, Xiaowei Shi, Li Tan, and Juan Ren Copyright © 2015 Yanxia Sui et al. All rights reserved. EMT-Inducing Molecular Factors in Gynecological Cancers Wed, 19 Aug 2015 13:14:19 +0000 Gynecologic cancers are the unregulated growth of neoplastic cells that arise in the cervix, ovaries, fallopian tubes, uterus, vagina, and vulva. Although gynecologic cancers are characterized by different signs and symptoms, studies have shown that they share common risk factors, such as smoking, obesity, age, exposure to certain chemicals, infection with human immunodeficiency virus (HIV), and infection with human papilloma virus (HPV). Despite recent advancements in the preventative, diagnostic, and therapeutic interventions for gynecologic cancers, many patients still die as a result of metastasis and recurrence. Since mounting evidence indicates that the epithelial-mesenchymal transition (EMT) process plays an essential role in metastatic relapse of cancer, understanding the molecular aberrations responsible for the EMT and its underlying signaling should be given high priority in order to reduce cancer morbidity and mortality. Loredana Campo, Catherine Zhang, and Eun-Kyoung Breuer Copyright © 2015 Loredana Campo et al. All rights reserved. Analysis of the Influence of Hormone Replacement Therapy on Osteocalcin Gene Expression in Postmenopausal Women Wed, 19 Aug 2015 12:59:38 +0000 Background. Osteocalcin (OC) contributes to the process of bone mineralization. Present study was designed to investigate the changes in OC gene expression of postmenopausal women treated with hormone replacement therapy (HRT). Study was also designed to evaluate OC gene expression in cells which are not part of connective tissue. Material and Methods. Research was carried out on 30 postmenopausal women not treated and 30 treated with HRT. Examination of OC gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Densitometry was conducted on femur and mandible. Results. Tests revealed OC gene expression in BEL and PBL. BMD was higher in groups treated with HRT. Assessment of correlation between the OC gene expression in BEL and BMD of mandible revealed significant positive relation. Conclusions. OC gene expression can be stated BEL and PBL. Analysis of correlation between OC gene expression in oral cavity and mandible BMD showed significant correlation between local OC expression and local bone metabolism. The relation between OC gene expression and bone metabolism is complex and further research is needed to clear all of the uncertainties. Mansur Rahnama, Izabela Jastrzębska-Jamrogiewicz, Rafał Jamrogiewicz, and Grzegorz Trybek Copyright © 2015 Mansur Rahnama et al. All rights reserved. Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro Wed, 19 Aug 2015 12:59:26 +0000 Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells’ metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia. Yanfen Zou, Xiang Yu, Jing Lu, Ziyan Jiang, Qing Zuo, Mingsong Fan, Shiyun Huang, and Lizhou Sun Copyright © 2015 Yanfen Zou et al. All rights reserved. Preimplantation Exposure to Bisphenol A and Triclosan May Lead to Implantation Failure in Humans Wed, 19 Aug 2015 12:57:25 +0000 Endocrine disrupting chemicals (EDCs) are chemicals that have the capacity to interfere with normal endocrine systems. Two EDCs, bisphenol A (BPA) and triclosan (TCS), are mass-produced and widespread. They both have estrogenic properties and similar chemical structures and pharmacokinetic features and have been detected in human fluids and tissues. Clinical evidence has suggested a positive association between BPA exposure and implantation failure in IVF patients. Studies in mouse models have suggested that preimplantation exposure to BPA and TCS can lead to implantation failure. This paper reviews the relationship between preimplantation exposure to BPA and TCS and implantation failure and discusses the remaining problems and possible solutions. Mu Yuan, Ming-Zhu Bai, Xu-Feng Huang, Yue Zhang, Jing Liu, Min-Hao Hu, Wei-Qian Zheng, and Fan Jin Copyright © 2015 Mu Yuan et al. All rights reserved. MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells Wed, 19 Aug 2015 12:53:11 +0000 We applied in the previous study miRNA microarray screening analysis to identify several differentially expressed miRNAs, including miR-183 in normal, eutopic, and ectopic endometrium. Knockdown of miR-183 expression induced the invasiveness and inhibition of apoptosis in endometrial stromal cells. The current study aims to identify the miR-183 targets with relevance to cell functions in endometrial stromal cells, to verify the interaction of miR-183 with its target genes, and to confirm the role of miR-183 in the process of endometriosis. Using microarray analysis, we identified 27 differentially expressed genes (19 were upregulated and 8 downregulated), from which we selected 4 downregulated genes (ITGB1, AMIGO2, VAV3, and PSEN2) based on GO databases for functional analysis and significant pathway analysis. Western blotting analyses showed that integrin β1 (ITGB1), but not AMIGO2, was affected by miR-183 overexpression, whereas no protein expression of VAV3 and PSEN2 was detected. Luciferase reporter assay verified that ITGB1 is a target gene of miR-183. Moreover, we found that ITGB1 is overexpressed in the endometrium of endometriosis patients. Furthermore, overexpression of ITGB1 rescued the repressive effects of miR-183 on the invasiveness of endometrial stromal cells. These findings, together with the fact that ITGB1 is a critical factor for cell adhesion and invasiveness, suggest that miR-183 may be involved in the development of endometriosis by regulating ITGB1 in endometrial stromal cells. Jie Chen, Lin Gu, Jie Ni, Ping Hu, Kai Hu, and Ying-Li Shi Copyright © 2015 Jie Chen et al. All rights reserved. Paracrine Regulation of Steroidogenesis in Theca Cells by Granulosa Cells Derived from Mouse Preantral Follicles Wed, 19 Aug 2015 12:47:05 +0000 Interaction partners of follicular cells play a significant role in steroidogenesis, follicular formation, and development. Androgen secreted by theca cells (TCs) can initiate follicle development and ovulation and provide precursor materials for estrogen synthesis. Therefore, studies on ovarian microenvironment will not only lead to better understanding of the steroidogenesis but also have clinical significance for ovarian endocrine abnormalities such as hyperandrogenism in polycystic ovary syndrome (PCOS). This study applied the Transwell coculture model to investigate if the interaction between granulosa and theca cells may affect androgen production in theca cells. Concentrations of testosterone and androstenedione in the spent medium were measured by radioimmunoassay and enzyme linked immunosorbent assay, respectively. The results show that the coculture with granulosa cells (GCs) increases steroidogenesis in TCs. In addition, testosterone and androstenedione productions in response to LH stimulation were also increased in the coculture model. Significantly increased mRNA expressions of steroidogenic enzymes (Star, Cyp11a1, Cyp17a1, and Hsd3b2) were observed in the cocultured TCs. Thus, GCs were capable of promoting steroidogenesis and LH responsiveness in TCs. This study provided a basis for further exploration of ovarian endocrine mechanism and pathologies. Xiaoqiang Liu, Pengyun Qiao, Aifang Jiang, Junyi Jiang, Haiyan Han, Li Wang, and Chune Ren Copyright © 2015 Xiaoqiang Liu et al. All rights reserved. Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells Wed, 19 Aug 2015 12:46:50 +0000 UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality. Hongshan Ge, Fan Zhang, Dan Shan, Hua Chen, Xiaona Wang, Chao Ling, HaiTao Xi, Jianying Huang, ChunFang Zhu, and Jeiqiang Lv Copyright © 2015 Hongshan Ge et al. All rights reserved. BRCA1 185delAG Mutation Enhances Interleukin-1β Expression in Ovarian Surface Epithelial Cells Wed, 19 Aug 2015 12:45:02 +0000 Familial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real-time PCR, western blot, ELISA, luciferase reporter, and siRNA assays. We found that BRAT cells expressed increased cellular and secreted levels of active IL-1β. BRAT-expressing OSE cells exhibited 3-fold enhanced IL-1β mRNA expression, transcriptionally regulated, in part, through CREB sites within the (−1800) to (−900) region of its promoter. In addition to transcriptional regulation, BRAT-mediated IL-1β expression appears dualistic through enhanced inflammasome-mediated caspase-1 cleavage and activation of IL-1β. Further investigation is warranted to elucidate the molecular mechanism(s) of BRAT-mediated IL-1β expression since increased IL-1β expression may represent an early step contributing to OC. Kamisha T. Woolery, Mai Mohamed, Rebecca J. Linger, Kimberly P. Dobrinski, Jesse Roman, and Patricia A. Kruk Copyright © 2015 Kamisha T. Woolery et al. All rights reserved. Lesser-Known Molecules in Ovarian Carcinogenesis Mon, 03 Aug 2015 11:17:59 +0000 Currently, the deciphering of the signaling pathways brings about new advances in the understanding of the pathogenic mechanism of ovarian carcinogenesis, which is based on the interaction of several molecules with different biochemical structure that, consequently, intervene in cell metabolism, through their role as regulators in proliferation, differentiation, and cell death. Given that the ensemble of biomarkers in OC includes more than 50 molecules the interest of the researchers focuses on the possible validation of each one’s potential as prognosis markers and/or therapeutic targets. Within this framework, this review presents three protein molecules: ALCAM, c-FLIP, and caveolin, motivated by the perspectives provided through the current limited knowledge on their role in ovarian carcinogenesis and on their potential as prognosis factors. Their structural stability, once altered, triggers the initiation of the sequences characteristic for ovarian carcinogenesis, through their role as modulators for several signaling pathways, contributing to the disruption of cellular junctions, disturbance of pro-/antiapoptotic equilibrium, and alteration of transmission of the signals specific for the molecular pathways. For each molecule, the text is built as follows: (i) general remarks, (ii) structural details, and (iii) particularities in expression, from different tumors to landmarks in ovarian carcinoma. Ludmila Lozneanu, Elena Cojocaru, Simona Eliza Giuşcă, Alexandru Cărăuleanu, and Irina-Draga Căruntu Copyright © 2015 Ludmila Lozneanu et al. All rights reserved. The Impact of Endometriosis on the Health of Women Tue, 21 Jul 2015 09:47:58 +0000 Claude L. Hughes, Warren G. Foster, Sanjay K. Agarwal, and Liselotte Mettler Copyright © 2015 Claude L. Hughes et al. All rights reserved. Clinical Outcome after Colonic Resection in Women with Endometriosis Wed, 15 Jul 2015 13:54:01 +0000 Background. In severe forms of endometriosis, the colon or rectum may be involved. This study evaluated the functional results and long-term outcome after laparoscopic colonic resection for endometriosis. Patients and Methods. Questionnaire survey with 24 women who had experienced typical symptoms, including pelvic pain, infertility, and endometriotic lesions in the bowel and undergone laparoscopic surgery, including low anterior resection, from 2009 to 2012, was conducted. Results. Information about the postoperative outcome was obtained from 22 women and was analyzed statistically. Twenty-one had undergone low anterior resection; one patient required a primary Hartmann procedure due to a rectovaginal fistula. The conversion rate was 4.5%. Major complications occurred in one patient, including an anastomotic leakage, and a Hartmann procedure was carried out subsequently in this patient. The symptoms of pain during defecation, pelvic pain, dyspareunia, dysmenorrhea, and hematochezia showed clear improvement one year after the operation and at the time of the questionnaire. Conclusion. Laparoscopic low anterior resection for deeply infiltrative endometriosis is technically demanding but feasible and safe, and it improves the clinical symptoms of endometriosis in the bowel. Bettina Klugsberger, Andreas Shamiyeh, Peter Oppelt, Christina Jabkowski, Wolfgang Schimetta, and Dietmar Haas Copyright © 2015 Bettina Klugsberger et al. All rights reserved. Pregnancy Rate after Controlled Ovarian Hyperstimulation and Intrauterine Insemination for the Treatment of Endometriosis following Surgery Sun, 12 Jul 2015 08:19:16 +0000 Objective. To compare pregnancy rate after controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) with no treatment in patients with endometriosis-associated infertility treated with laparoscopy. Design. A clinical cohort study. Setting. University-level tertiary care center. Patients. 238 women with various stages of endometriosis after laparoscopic treatment. Interventions. Either COH-IUI or follow-up for 12 months. Main Outcome Measures. The primary outcome measures were clinical pregnancy and live birth rate. Predictive factors evaluated were female age, maternal BMI, and duration of infertility. Results. The pregnancy rate attained after the integrated laparoscopy–COH-IUI approach was 53.4%, while it was significantly lower (38.5%) in the control group. Similarly, a significant difference was observed in live births (48.3% versus 34.2%). Patients with severe endometriosis were less likely to achieve pregnancy (38%) and live birth (35%) than their counterparts with milder forms (57% and 53%). Conclusions. In patients with endometriosis-based infertility, surgery followed by COH-IUI is more effective than surgery alone. Attila Keresztúri, Zoltan Kozinszky, József Daru, Norbert Pásztor, János Sikovanyecz, János Zádori, Virág Márton, Sándor Koloszár, János Szöllősi, and Gábor Németh Copyright © 2015 Attila Keresztúri et al. All rights reserved. The Surgical Treatment of Severe Endometriosis Positively Affects the Chance of Natural or Assisted Pregnancy Postoperatively Sun, 12 Jul 2015 08:02:01 +0000 Objective. To report reproductive outcomes following laparoscopic surgical excision of histologically confirmed r-ASRM stage III-IV endometriosis. Study Design. A retrospective cohort study was performed at the Royal Hospital for Women, a university teaching hospital, Sydney, Australia. Women who had fertility-preserving laparoscopic excision of stage III-IV endometriosis from 1997 to 2009 were contacted regarding reproductive outcomes. Results. In the study period, 355 women underwent surgery for stage III-IV endometriosis. Follow-up data are available for 253/355 (71%) women. Postoperatively, 142/253 (56%) women attempted to conceive with a conception rate of 104/142 (73%). Confidence intervals for pregnancy for women who were attempting conception (including the nonresponders) range from 104/262 (40%) to 224/262 (85%). Median time to conception was 12 months. No positive prognostic factors for pregnancy were identified on regression analyses. Conclusions. These data provide information to women with suspected severe disease preoperatively concerning their likely postoperative fertility outcomes. Ours is a population with severe endometriosis, rather than an infertile population with endometriosis, so caution needs to be applied when applying these data to women with fertility issues alone. Erin M. Nesbitt-Hawes, Neil Campbell, Peta E. Maley, Haryun Won, Dona Hooshmand, Amanda Henry, William Ledger, and Jason A. Abbott Copyright © 2015 Erin M. Nesbitt-Hawes et al. All rights reserved. Pathophysiology and Immune Dysfunction in Endometriosis Sun, 12 Jul 2015 07:34:01 +0000 Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. Soo Hyun Ahn, Stephany P. Monsanto, Caragh Miller, Sukhbir S. Singh, Richard Thomas, and Chandrakant Tayade Copyright © 2015 Soo Hyun Ahn et al. All rights reserved. Reduction in Endometrioma Size with Three Months of Aromatase Inhibition and Progestin Add-Back Sun, 12 Jul 2015 06:55:00 +0000 The purpose of this study was to assess the impact of 3 months of aromatase inhibition together with progestin add-back on ovarian endometrioma size. This prospective cohort study was performed at University Medical Center (UC San Diego). Women trying to conceive were excluded. After informed consent, all women were treated with the aromatase inhibitor letrozole (5 mg/d) with norethindrone acetate (5 mg/d) add-back for 3 months. Pre- and posttreatment assessments of endometrioma sizes were performed by ultrasound. The impact of treatment on pain was determined using the patient assessed endpoints of the Biberoglu and Behrman scale. These included assessing dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain each on a scale from 0 to 3. The primary endpoint of this study was the change in ultrasound documented endometrioma size. Fourteen endometriomas in 8 consecutive women were treated for 3 m. Mean endometrioma diameter decreased 50% from 4.6 ± 1.6 cm to 2.3 ± 1.6 cm (mean ± SD). This represents a 75% decrease in endometrioma volume. Endometriosis symptoms of dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain also improved with treatment. In conclusion, a 3-month course of high dose aromatase inhibition with progestin add-back significantly reduces ovarian endometrioma size and warrants further investigation. Sanjay K. Agarwal and Warren G. Foster Copyright © 2015 Sanjay K. Agarwal and Warren G. Foster. All rights reserved. Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies Thu, 09 Jul 2015 11:35:31 +0000 The assisted reproductive technologies, particularly in vitro fertilization (IVF), represent the most efficient and successful means of overcoming infertility associated with endometriosis. Although older studies suggest that IVF outcomes are compromised in endometriosis patients, more contemporary reports show no differences compared to controls. The exception may be evidence of poorer outcomes and diminished ovarian response in women with advanced disease, particularly those with significant ovarian involvement or prior ovarian surgery. Prolonged pre-IVF cycle suppressive medical therapy, particularly gonadotropin releasing hormone agonists, appears to improve success rates in a subset of endometriosis patients. However, as of yet, there is no diagnostic marker to specifically identify those who would most benefit from this approach. Pre-IVF cycle surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. Precycle resection of ovarian endometriomas does not have benefit and should only be performed for gynecologic indications. Indeed, there is a large body of evidence to suggest that this procedure may have a deleterious impact on ovarian reserve and response. A dearth of appropriately designed trials makes development of definitive treatment paradigms challenging. Eric S. Surrey Copyright © 2015 Eric S. Surrey. All rights reserved. An Update on Surgical versus Expectant Management of Ovarian Endometriomas in Infertile Women Thu, 09 Jul 2015 11:32:07 +0000 Ovarian endometriomas are a common manifestation of endometriosis that can represent a more severe stage of the disease. There is much debate over the treatment of these cysts in infertile women, particularly before use of assisted reproductive technologies. Evidence exists that supports surgical excision of ovarian endometriomas, as well as evidence that cautions against surgical intervention. Certain factors need to be examined closely before proceeding with surgery or continuing with expectant management. These include the patient’s symptoms, age, ovarian reserve, size and laterality of the cyst, prior surgical treatment, and level of suspicion for malignancy. The most recent evidence appears to suggest that certain patient profiles may benefit from proceeding directly to in vitro fertilization (IVF). These include symptomatic infertile patients, especially those that are older, those that have diminished ovarian reserve, those that have bilateral endometriomas, or those that have had prior surgical treatment. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman’s ovarian reserve. Nevertheless, the presence of an endometrioma does not appear to adversely affect IVF outcomes, and surgical excision of endometriomas does not appear to improve IVF outcomes. Regardless of treatment plan, infertile patients with endometriomas must be counseled appropriately before choosing either treatment path. Sanaz Keyhan, Claude Hughes, Thomas Price, and Suheil Muasher Copyright © 2015 Sanaz Keyhan et al. All rights reserved. How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice Thu, 09 Jul 2015 11:23:25 +0000 Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women’s lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis. A. Vanhie, A. Fassbender, D. O, C. Tomassetti, C. Meuleman, K. Peeraer, S. Debrock, and Th. D’Hooghe Copyright © 2015 A. Vanhie et al. All rights reserved. Update on Biomarkers for the Detection of Endometriosis Thu, 09 Jul 2015 11:03:32 +0000 Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium. Amelie Fassbender, Richard O. Burney, Dorien F. O, Thomas D’Hooghe, and Linda Giudice Copyright © 2015 Amelie Fassbender et al. All rights reserved. Abnormal Expression of Prostaglandins E2 and F2α Receptors and Transporters in Patients with Endometriosis Thu, 09 Jul 2015 10:53:31 +0000 Objective. To investigate the level of expression of prostaglandin receptivity and uptake factors in eutopic and ectopic endometrium of women with endometriosis. Design. Prospective study. Setting. Human reproduction research laboratory. Patients. Seventy-eight patients with endometriosis and thirty healthy control subjects. Intervention(s). Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery. Main Outcome Measure(s). Real-time polymerase chain reaction assay of mRNA encoding prostaglandin E2 receptors (EP1, EP2, EP3, and EP4), prostaglandin F2α receptor (FP), prostaglandin transporter (PGT), and multidrug resistance-associated protein 4 (MRP4); immunohistochemical localization of expressed proteins. Results. Marked increases in receptors EP3, EP4, and FP and transporters PGT and MRP4 in ectopic endometrial tissue were noted, without noticeable change associated with disease stage. An increase in EP3 expression and decreases in FP and PGT were observed in the eutopic endometrium of endometriosis patients in conjunction with the phases of the menstrual cycle. Conclusion(s). This study is the first to demonstrate a possible relationship between endometriosis and enhanced prostaglandin activity. In view of the wide range of prostaglandin functions, increasing cell receptivity and facilitating uptake in endometrial tissue could contribute to the initial steps of overgrowth and have an important role to play in the pathogenesis and symptoms of this disease. Halima Rakhila, Nathalie Bourcier, Ali Akoum, and Marc Pouliot Copyright © 2015 Halima Rakhila et al. All rights reserved. Developing a Noninvasive Procedure Using Labeled Monoclonal Antibody Anti-VEGF (Bevacizumab) for Detection of Endometriosis Thu, 09 Jul 2015 09:22:07 +0000 The off-label use of bevacizumab labeled with 99mTc as a new radiopharmaceutical for imaging of endometriosis is a promising noninvasive, new clinical procedure. The bevacizumab in monoclonal antibodies targeted at vascular endothelial growth factor (VEGF) is superexpressed in cases of endometriosis. In this study we evaluate the imaging of endometriosis lesion in rats (induced to endometriosis) using bevacizumab-99mTc. The results showed that bevacizumab-99mTc imaged the lesion and support his use for Nuclear Medicine applied to gynecology. Also the results appointed that this radiopharmaceutical has a hepatobiliary excretion. It is important to notice that the dose used was almost 0,01% of the usual dose for the bevacizumab. Daniel Escorsim Machado, Jamila Alessandra Perini, Margarida Maria Camoes Orlando, and Ralph Santos-Oliveira Copyright © 2015 Daniel Escorsim Machado et al. All rights reserved. Fixation of Light Weight Polypropylene Mesh with n-Butyl-2-cyanocrylate in Pelvic Floor Surgery: Experimental Design Approach in Sheep for Effectiveness Evaluation Sun, 28 Jun 2015 10:54:48 +0000 Objective. The aim of this study was to find a proper experimental design and to evaluate n-butyl-2-cyanoacrylate (Histoacryl) as a fixation method for a light-weight and large pore PP mesh (Synthetic PP Mesh-1) using the sheep as an animal model. Methods. Posterior vaginal implantation by means of episiotomy was used to implant 8 ewes which were evaluated macroscopically and histologically at 3 months () and 6 months () post-surgery. In previous pilot studies anterior vaginal implantation was evaluated, as well as different synthetic mesh materials, sizes and fixation methods ( to 3) during three weeks. In all cases a clinical evaluation of the animal was performed. Results. A reduction in the mesh size (Synthetic PP Mesh-1) together with precise application of the surgical glue Histoacryl to fix the mesh yielded significantly better histocompatibility results () compared to larger size or other fixation methods. Conclusion. The combination of Synthetic PP Mesh-1 with Histoacryl offered a high degree of graft integration without vaginal ulceration and a minimal foreign body reaction, being the sheep a proper animal model to test these types of medical devices. Sandra Barbosa, Tania Nieves, Félix García, Eva Cepeda, Xavier Moll, Alberto Marco, Christine Weis, Pau Turon, and Patri Vergara Copyright © 2015 Sandra Barbosa et al. All rights reserved. Challenges in Gynecological Cancer: Biology, Diagnosis, Surgical, and Medical Treatment Mon, 22 Jun 2015 07:39:28 +0000 Ignacio Zapardiel, Shalini Rajaram, Elisa Piovano, and Marco Petrillo Copyright © 2015 Ignacio Zapardiel et al. All rights reserved. Microvessels Density in Uterine Leiomyosarcoma Tue, 16 Jun 2015 13:55:15 +0000 Uterine leiomyosarcomas (LMS) are rare tumors typically presenting rapid growth and unfavorable outcome. Nowadays the results of uterine LMS treatment do not meet expectations. Angiogenesis is one of processes investigated to be target for future treatment. The aim of the research was to assess microvessels density (MVD) in tumor samples collected from 50 patients with histological confirmed uterine leiomyosarcoma and to investigate statistical relations between MVD, patients survival, and FIGO stage of tumor. The assessment was carried out using immunohistochemistry methods with anti-CD34 antibody. No significant difference in MVD between FIGO stages was observed. Furthermore, contrary to many other malignancies, we found no significant relation between MVD and patients overall and 2-year survival. Results obtained in the study suggest that processes on vascular mimicry and mesenchymal to epithelial transition (MET) may play important role in development of LMS. No statistical relation between MVD and survival leads to conclusion that not only angiogenesis but other mechanisms as well should be taken into consideration in planning future research. Marcin Bobiński, Wiesława Bednarek, Justyna Szumiło, Marek Cybulski, Grzegorz Polak, and Jan Kotarski Copyright © 2015 Marcin Bobiński et al. All rights reserved. Glycosyltransferases as Markers for Early Tumorigenesis Tue, 16 Jun 2015 13:52:10 +0000 Background. Glycosylation is the most frequent posttranslational modification of proteins and lipids influencing inter- and intracellular communication and cell adhesion. Altered glycosylation patterns are characteristically observed in tumour cells. Normal and altered carbohydrate chains are transferred to their acceptor structures via glycosyltransferases. Here, we present the correlation between the presence of three different glycosyltransferases and tumour characteristics. Methods. 235 breast cancer tissue samples were stained immunohistochemically for the glycosyltransferases N-acetylgalactosaminyltransferase 6 (GALNT6), β-1,6-N-acetylglucosaminyltransferase 2 (GCNT2), and ST6 (α-N-acetyl-neuraminyl-2,3-β-galactosyl-1,3)-N-acetylgalactosamine α-2,6-sialyltransferase 1 (ST6GALNac1). Staining was evaluated by light microscopy and was correlated to different tumour characteristics by statistical analysis. Results. We found a statistically significant correlation for the presence of glycosyltransferases and tumour size and grading. Specifically smaller tumours with low grading revealed the highest incidences of glycosyltransferases. Additionally, Her4-expression but not pHer4-expression is correlated with the presence of glycosyltransferases. All other investigated parameters could not uncover any statistically significant reciprocity. Conclusion. Here we show, that glycosyltransferases can identify small tumours with well-differentiated cells; hence, glycosylation patterns could be used as a marker for early tumourigenesis. This assumption is supported by the fact that Her4 is also correlated to glycosylation, whereas the activated form of Her4 does not show such a connection with glycosylation. Ulrich Andergassen, Friederike Liesche, Alexandra C. Kölbl, Matthias Ilmer, Stefan Hutter, Klaus Friese, and Udo Jeschke Copyright © 2015 Ulrich Andergassen et al. All rights reserved. Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment? Tue, 16 Jun 2015 13:05:04 +0000 Endometrial carcinoma is the most common gynecological tumor worldwide. It can be the presenting malignancy, acting as the harbinger, of an undiagnosed hereditary syndrome. Up to 50% of females with Lynch syndrome present in this manner. Differentiation between Lynch, Muir-Torre, and Cowden syndromes can at times be challenging due to the overlapping features. Our review emphasizes on the strengths, pitfalls, and limitations of microscopic features as well as immunohistochemical and polymerase chain reaction- (PCR-) based tests used by laboratories to screen for DNA mismatch repair (MMR) and PTEN gene mutations in patients to enable a more targeted and cost effective approach in the use of confirmatory gene mutational analysis tests. This is crucial towards initiating timely and appropriate surveillance measures for the patient and affected family members. We also review the evidence postulating on the possible inclusion of uterine serous carcinoma as part of the spectrum of malignancies seen in hereditary breast and ovarian carcinoma syndrome, driven by mutations in BRCA1/2. Adele Wong and Joanne Ngeow Copyright © 2015 Adele Wong and Joanne Ngeow. All rights reserved. Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43 Tue, 16 Jun 2015 08:10:45 +0000 Objects. To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. Methods. Cell proliferation and apoptosis of human endometrial stromal cells (HESCs) and glandular cells (HEGCs) treated with LNG in a dose- and time-dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. Results. 5 × 10−5 mol/L LNG revealed a time-dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 × 10−5 mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. Conclusions. LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment. Xiaomiao Zhao, Xueliang Tang, Tingting Ma, Miao Ding, Lijuan Bian, Dongmei Chen, Yangzhi Li, Liangan Wang, Yanyan Zhuang, Meiqing Xie, and Dongzi Yang Copyright © 2015 Xiaomiao Zhao et al. All rights reserved. Clinical Usefulness of Immunohistochemical Staining of p57kip2 for the Differential Diagnosis of Complete Mole Tue, 16 Jun 2015 07:55:46 +0000 Objective. Can polymer-based immunohistochemical staining of replace DNA analysis as an inexpensive means of differentiating complete mole from partial mole or hydropic abortion? Methods and Materials. Original paraffin-embedded tissue blocks from 14 equivocal cases were turned over to our laboratory and examined by immunohistochemical staining of . Results. Four of the 14 cases showed clearly negative nuclear staining in cytotrophoblasts and villous stromal cells: these results were fully concordant with the control staining. The remaining 10 cases showed apparently positive staining in cytotrophoblasts and villous stromal cells. Without DNA analysis we are able to clearly differentiate the 4 cases of complete mole among the 14 equivocal cases. During follow-up, secondary low-risk gestational trophoblastic neoplasia (GTN) developed in 1 of the 4 cases of complete mole: the GTN was treated by single-agent chemotherapy. No subsequent changes were observed during follow-up in the other cases. Conclusion. Polymer-based immunohistochemical staining of (paternally imprinted gene, expressed from maternal allele) is a very effective method that can be used to differentiate androgenetic complete mole from partial mole and hydropic abortion. We might be able to avoid the cost of DNA analysis. Shigeru Sasaki, Yasushi Sasaki, Toshiaki Kunimura, Akihiko Sekizawa, Yoshihiro Kojima, and Koichi Iino Copyright © 2015 Shigeru Sasaki et al. All rights reserved. A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF Tue, 16 Jun 2015 07:36:02 +0000 Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients’ characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). Conclusion. The combination protocol does not provide additional efficacy. Gayem İnayet Turgay Çelik, Havva Kömür Sütçü, Yaşam Kemal Akpak, and Münire Erman Akar Copyright © 2015 Gayem İnayet Turgay Çelik et al. All rights reserved. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer Tue, 16 Jun 2015 07:20:01 +0000 Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early and late stages . Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics. Animesh Barua, Aparna Yellapa, Janice M. Bahr, Malavika K. Adur, Chet W. Utterback, Pincas Bitterman, Sanjib Basu, Sameer Sharma, and Jacques S. Abramowicz Copyright © 2015 Animesh Barua et al. All rights reserved. Cervical Cancer Prevention: New Frontiers of Diagnostic Strategies Wed, 10 Jun 2015 08:28:48 +0000 Massimo Origoni, Walter Prendiville, and Evangelos Paraskevaidis Copyright © 2015 Massimo Origoni et al. All rights reserved. Underscreened Women Remain Overrepresented in the Pool of Cervical Cancer Cases in Spain: A Need to Rethink the Screening Interventions Tue, 09 Jun 2015 07:09:25 +0000 Objective. Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000–2011. Methods. 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). Results. History of cytology was registered in 26.2% of CC cases and in 78% of the control women () and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis ( CI 95%: 1.2–5.6) and to have normal cytology results in previous screenings ( CI 95%: 1.2–4.5). FIGO II–IV cases were more common among older women (older than 60 years). Conclusions. Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden. Raquel Ibáñez, María Alejo, Neus Combalia, Xavier Tarroch, Josefina Autonell, Laia Codina, Montserrat Culubret, Francesc Xavier Bosch, and Silvia de Sanjosé Copyright © 2015 Raquel Ibáñez et al. All rights reserved. miR-34a and miR-125b Expression in HPV Infection and Cervical Cancer Development Tue, 09 Jun 2015 06:58:32 +0000 We aimed to characterize miR-125b and miR-34a expression in 114 women with different cervical lesions: normal epithelium with ( = 20) and without ( = 29) HPV infection; LSIL ( = 28); HSIL ( = 29); and ICC ( = 8). miRNA expression analysis was performed by comparing the distinct groups with the reference group (women with normal epithelium without HPV). For miR-125b, we observed a twofold ( = 2.11; = 0.038) increased expression among women with normal epithelium with HPV infection and a trend of downregulation in different cervical lesions including an 80% reduction ( = 0.21; = 0.004) in ICC. Similarly, miR-34a expression analysis revealed an increased expression ( = 1.69; = 0.049) among women with normal cervix and HPV infection, and despite no significant correlation with cervical lesions, its expression was increased by twofold ( = 2.08; = 0.042) in ICC. Moreover, miR-125b levels were able to predict invasive cancers with 88% sensitivity and 69% specificity. Results showed that while miR-34a expression seems to be correlated with invasive cervical cancer, miR-125b expression is significantly changed within the different cervical lesions and their levels should be further investigated as possible predictive/prognostic biomarkers using a noninvasive approach. Joana Ribeiro, Joana Marinho-Dias, Paula Monteiro, Joana Loureiro, Inês Baldaque, Rui Medeiros, and Hugo Sousa Copyright © 2015 Joana Ribeiro et al. All rights reserved. Accuracy of Colposcopically Directed Biopsy: Results from an Online Quality Assurance Programme for Colposcopy in a Population-Based Cervical Screening Setting in Italy Tue, 09 Jun 2015 06:48:25 +0000 Purpose. To report the accuracy of colposcopically directed biopsy in an internet-based colposcopy quality assurance programme in northern Italy. Methods. A web application was made accessible on the website of the regional Administration. Fifty-nine colposcopists out of the registered 65 logged in, viewed a posted set of 50 digital colpophotographs, classified them for colposcopic impression and need for biopsy, and indicated the most appropriate site for biopsy with a left-button mouse click on the image. Results. Total biopsy failure rate, comprising both nonbiopsy and incorrect selection of biopsy site, was 0.20 in CIN1, 0.11 in CIN2, 0.09 in CIN3, and 0.02 in carcinoma. Errors in the selection of biopsy site were stable between 0.08 and 0.09 in the three grades of CIN while decreasing to 0.01 in carcinoma. In multivariate analysis, the risk of incorrect selection of biopsy site was 1.97 for CIN2, 2.52 for CIN3, and 0.29 for carcinoma versus CIN1. Conclusions. Although total biopsy failure rate decreased regularly with increasing severity of histological diagnosis, the rate of incorrect selection of biopsy site was stable up to CIN3. In multivariate analysis, CIN2 and CIN3 had an independently increased risk of incorrect selection of biopsy site. Mario Sideri, Paola Garutti, Silvano Costa, Paolo Cristiani, Patrizia Schincaglia, Priscilla Sassoli de Bianchi, Carlo Naldoni, and Lauro Bucchi Copyright © 2015 Mario Sideri et al. All rights reserved. Current Advances in the Application of Raman Spectroscopy for Molecular Diagnosis of Cervical Cancer Tue, 09 Jun 2015 06:45:43 +0000 Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells, and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect premalignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical use and larger comprehensive studies are required to fully establish the role of Raman spectroscopy in the molecular diagnostics of cervical cancer. Inês Raquel Martins Ramos, Alison Malkin, and Fiona Mary Lyng Copyright © 2015 Inês Raquel Martins Ramos et al. All rights reserved. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study Tue, 09 Jun 2015 06:37:11 +0000 Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4–14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). Results. CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31–15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07–36.9), CIN3+ excision (OR 6.02, 95% CI 1.73–20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8–62.6; OR for other hrHPV types: 18.3, 95% CI 5.9–57.0). Conclusion. Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6–12 months of follow-up. Annarosa Del Mistro, Mario Matteucci, Egle Alba Insacco, GianLibero Onnis, Filippo Da Re, Lorena Baboci, Manuel Zorzi, and Daria Minucci Copyright © 2015 Annarosa Del Mistro et al. All rights reserved. HPV Testing from Dried Urine Spots as a Tool for Cervical Cancer Screening in Low-Income Countries Tue, 09 Jun 2015 05:53:22 +0000 Nowadays, several screening strategies are available to prevent cervical cancer, but inadequate resources, sociocultural barriers, and sampling issues impede their success in low-income countries. To overcome these issues, this study aimed to evaluate the performance of human papillomavirus (HPV) testing from dried urine spots (DUS). Eighty-eight urine samples (including 56 HPV DNA positive specimens) were spotted on filter paper, dried, and stored in paper-bags. HPV DNA was detected from the DUS after 1 week and 4 weeks of storage using a polymerase chain reaction (PCR) assay. The sensitivity, specificity, and concordance of the DUS-based HPV test were evaluated by comparing the results with those of HPV testing on fresh urine samples as the gold standard. The sensitivity of the test was 98.21% (95% CI: 90.56–99.68) for DUS stored for 1 week and 96.42% (95% CI: 87.88–99.01) for DUS stored for 4 weeks. The specificity was 100% (95% CI: 89.28–100) at both time points. The concordance between DUS and fresh urine HPV testing was “almost perfect” using the κ statistic. These preliminary data suggest that a DUS-based assay could bypass sociocultural barriers and sampling issues and therefore could be a suitable, effective tool for epidemiological surveillance and screening programs, especially in low-income countries. Elena Rosanna Frati, Marianna Martinelli, Ester Fasoli, Daniela Colzani, Silvia Bianchi, Sandro Binda, Pierfranco Olivani, and Elisabetta Tanzi Copyright © 2015 Elena Rosanna Frati et al. All rights reserved. The Role of Overweight and Obesity in In Vitro Fertilization Outcomes of Poor Ovarian Responders Wed, 27 May 2015 09:10:40 +0000 Objective. Obesity is a worldwide concern with detrimental health effects including decreased fecundity. However, obesity’s impact on in vitro fertilization (IVF) is inconclusive and there is little data concerning poor ovarian responders (POR). This study explored the effects of overweight and obesity on IVF outcomes of POR. Design. We retrospectively evaluated 188 POR undergoing IVF cycles. Methods. Patients were categorized into three groups. Group 1 was normal weight POR (18.5–24.9 kg/m2, ); Group 2 was overweight POR (25.0–29.9 kg/m2, ); and Group 3 was obese POR (≥30.0 kg/m2, ). Main measured outcomes included IVF outcomes. Results. The oocyte maturity, total gonadotropin dose-duration, and cycle cancellation rates were similar. Obese women had significantly decreased LH levels. LH < 4 mIU/mL had a sensitivity (62%) and a specificity (86%) for IVF failure (AUC: 0.71). Fertilization rates of obese subjects were significantly lower than normal and overweight subjects (). Obese women’s clinical pregnancy rates were significantly lower (15%) than normal weight women (33.3%, ). Conclusions. Despite similar counts of recruited mature oocytes, obese POR women had decreased fertilization and clinical pregnancy rates. Obesity rather than overweight significantly decreased IVF outcomes in POR. Fisun Vural, Birol Vural, and Yiğit Çakıroğlu Copyright © 2015 Fisun Vural et al. All rights reserved. Sensitive Detection of Thirteen Bacterial Vaginosis-Associated Agents Using Multiplex Polymerase Chain Reaction Wed, 20 May 2015 11:29:10 +0000 Bacterial vaginosis (BV) is characterized by a polymicrobial proliferation of anaerobic bacteria and depletion of lactobacilli, which are components of natural vaginal microbiota. Currently, there are limited conventional methods for BV diagnosis, and these methods are time-consuming, expensive, and rarely allow for the detection of more than one agent simultaneously. Therefore, we conceived and validated a multiplex polymerase chain reaction (M-PCR) assay for the simultaneous screening of thirteen bacterial vaginosis-associated agents (BV-AAs) related to symptomatic BV: Gardnerella vaginalis, Mobiluncus curtisii, Mobiluncus mulieris, Bacteroides fragilis, Mycoplasma hominis, Atopobium vaginae, Ureaplasma urealyticum, Megasphaera type I, Clostridia-like bacteria vaginosis-associated bacteria (BVABs) 1, 2, and 3, Sneathia sanguinegens, and Mycoplasma genitalium. The overall validation parameters of M-PCR compared to single PCR (sPCR) were extremely high, including agreement of 99.1% and sensitivity, specificity, and positive predictive values of 100.0%, negative predictive value of 97.0%, accuracy of 99.3%, and agreement with Nugent results of 100.0%. The prevalence of BV-AAs was very high (72.6%), and simultaneous agents were detected in 53.0%, which demonstrates the effectiveness of the M-PCR assay. Therefore, the M-PCR assay has great potential to impact BV diagnostic methods in vaginal samples and diminish associated complications in the near future. Natália Malaguti, Larissa Danielle Bahls, Nelson Shozo Uchimura, Fabrícia Gimenes, and Marcia Edilaine Lopes Consolaro Copyright © 2015 Natália Malaguti et al. All rights reserved. Office Hysteroscopic Laser Enucleation of Submucous Myomas without Mass Extraction: A Case Series Study Mon, 18 May 2015 11:44:41 +0000 Background and Objectives. A new two-step hysteroscopic myomectomy carried out in the office setting and without anesthesia was feasible for the excision of submucous myomas. The objective of this study was to assess whether removal of submucous myomas from the uterine cavity after hysteroscopic laser enucleation is necessary. Methods. Between June 2009 and April 2013, all outpatients with symptomatic myomatosis (bleeding, pelvic pain, and infertility) assessed ultrasonographically were eligible to participate in a prospective study. All patients underwent office hysteroscopic enucleation of submucous myomas. Enucleated myomas were left in the uterine cavity. Neither anesthesia nor antibiotic prophylaxis was used. Results. Sixty-one women (mean age: 47.3 years) were included. Regardless of hysteroscopic localization and grading, all myomas were enucleated. The mean (standard deviation, SD) diameter of the myoma as measured by the ultrasound scan was 22.6 (8.5) mm. In 29 cases (47.5%), the diameter of the resected myoma was >20 mm and in 10 cases (16.4%) >30 mm. After a mean follow-up of 68.2 (16.5) days, none of the patients showed a residual myoma inside the uterine cavity. Conclusions. The present results indicate that leaving laser-enucleated submucous myoma in the uterine cavity is a feasible and safe therapeutic option. Sergio Haimovich, Maite López-Yarto, Julio Urresta Ávila, Alejandro Saavedra Tascón, José L. Hernández, and Ramón Carreras Collado Copyright © 2015 Sergio Haimovich et al. All rights reserved. Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer Mon, 18 May 2015 06:34:52 +0000 CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer. Marianne Kramer, Sandra Pierredon, Pascale Ribaux, Jean-Christophe Tille, Patrick Petignat, and Marie Cohen Copyright © 2015 Marianne Kramer et al. All rights reserved. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes Sun, 17 May 2015 14:19:54 +0000 More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making. Angela Toss, Chiara Tomasello, Elisabetta Razzaboni, Giannina Contu, Giovanni Grandi, Angelo Cagnacci, Russell J. Schilder, and Laura Cortesi Copyright © 2015 Angela Toss et al. All rights reserved. Prenatal Diagnosis of Central Nervous System Anomalies by High-Resolution Chromosomal Microarray Analysis Tue, 12 May 2015 12:37:37 +0000 The aims of this study were to evaluate the contribution of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with central nervous system (CNS) anomalies but normal chromosomal karyotype. A total of 46 fetuses with CNS anomalies with or without other ultrasound anomalies but normal karyotypes were evaluated by array-based comparative genomic hybridisation (aCGH) or single-nucleotide polymorphism (SNP) array. The result showed that CNVs were detected in 17 (37.0%) fetuses. Of these, CNVs identified in 5 (5/46, 10.9%) fetuses were considered to be likely pathogenic, and CNVs detected in 3 (3/46, 6.5%) fetuses were defined as being of uncertain clinical significance. Fetuses with CNS malformations plus other ultrasound anomalies had a higher rate of pathogenic CNVs than those with isolated CNS anomalies (13.6% versus 8.3%), but there was no significant difference (Fisher’s exact test, ). Pathogenic CNVs were detected most frequently in fetuses with Dandy-Walker syndrome (2/6, 33.3%) when compared with other types of neural malformations, and holoprosencephaly (2/7, 28.6%) ranked the second. CMA is valuable in prenatal genetic diagnosis of fetuses with CNS anomalies. It should be considered as part of prenatal diagnosis in fetuses with CNS malformations and normal karyotypes. Lijuan Sun, Qingqing Wu, Shi-Wen Jiang, Yani Yan, Xin Wang, Juan Zhang, Yan Liu, Ling Yao, Yuqing Ma, and Li Wang Copyright © 2015 Lijuan Sun et al. All rights reserved. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects Wed, 06 May 2015 07:57:32 +0000 In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan. C. L. Hughes, W. G. Foster, and S. K. Agarwal Copyright © 2015 C. L. Hughes et al. All rights reserved. Estradiol Valerate Pretreatment in Short Protocol GnRH-Agonist Cycles versus Combined Pretreatment with Oral Contraceptive Pills in Long Protocol GnRH-Agonist Cycles: A Randomised Controlled Trial Thu, 02 Apr 2015 16:28:22 +0000 The strategy of in vitro fertilization (IVF) procedures relies on the increasing pregnancy rate and decreasing the risk of premature ovulation and ovarian hyperstimulation syndrome. They are also designed to avoid weekend oocyte retrievals. Combined oral contraceptive (OC) pills are among the medicines used to accomplish these objectives. Alternatively, estradiol can be used instead of OC to obtain similar results. The aim of our study was to compare the differences in pregnancy rates (PRs), implantation rates, and miscarriage rates between a short agonist protocol with estradiol priming and a long protocol with combined OC. Of the 298 women who participated in this study, 134 achieved clinical pregnancies (45.0%). A higher PR (58.4%, , compared to 40.3%, ) was achieved in the long protocol after OC pretreatment group. The implantation rate was also higher for this group (37.8% versus 28.0%; ). The miscarriage rate was 15.0% for the long protocol after OC pretreatment group and 20.4% for the short agonist group . The short agonist protocol required a 5.7% lower human menopausal gonadotropin (hMG) dosage than the long protocol but surprisingly the number of oocytes retrieved was also smaller. Krzysztof Lukaszuk, Joanna Liss, Michal Kunicki, Waldemar Kuczynski, Ewa Pastuszek, Grzegorz Jakiel, Lukasz Plociennik, Krzysztof Zielinski, and Judyta Zabielska Copyright © 2015 Krzysztof Lukaszuk et al. All rights reserved. Induced Second Trimester Abortion and Associated Factors in Amhara Region Referral Hospitals Mon, 30 Mar 2015 10:18:51 +0000 Background. Although the vast majority of abortions are performed in the first trimester, still 10–15% of terminations of pregnancies have taken place in the second trimester period globally. As compared to first trimester, second trimester abortions are disproportionately contribute for maternal morbidity and mortality especially in low-resource countries where access to safe second trimester abortion is limited. The main aim of this study was to assess the prevalence and associated factors of induced second trimester abortion in Amhara region referral hospitals, northwest Ethiopia. Methods. Institution based cross-sectional study was conducted in Amhara region referral hospitals among 416 women who sought abortion services. Participants were selected using systematic sampling technique. Data were collected using pretested structured questionnaire through interviewing. After the data were entered and analyzed; variables which have value < 0.2 in bivariate analysis, not colinear, were entered into multiple logistic regressions to see the net effect with 95% CI and value < 0.05. Results. The prevalence of induced second trimester abortion was 19.2%. Being rural (AOR = 1.86 [95% CI = 1.11–3.14]), having irregular menstrual cycle (AOR = 1.76 [95% CI = 1.03–2.98]), not recognizing their pregnancy at early time (AOR = 2.05 [95% CI = 1.21–3.48]), and having logistics related problems (AOR = 2.37 [95% CI = 1.02–5.53]) were found to have statistically significant association with induced second trimester abortion. Conclusion. Induced second trimester abortion is high despite the availability of first trimester abortion services. Therefore, increase accessibility and availability of safe second trimester abortion services below referral level, counseling and logistical support are helpful to minimize late abortions. Amlaku Mulat, Hinsermu Bayu, Habtamu Mellie, and Amare Alemu Copyright © 2015 Amlaku Mulat et al. All rights reserved. Comparison of Clinical Outcomes Using “Elevate Anterior” versus “Perigee” System Devices for the Treatment of Pelvic Organ Prolapse Sun, 29 Mar 2015 12:40:19 +0000 Objective. This study aims to compare clinical outcomes using the Perigee versus Elevate anterior devices for the treatment of pelvic organ prolapse (POP). Study Design. One hundred and forty-one women with POP stages II to IV were scheduled for either Perigee () or Elevate anterior device (). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about quality of life and urinary symptoms. Results. Despite postoperative point C of Elevate group being significantly deeper than the Perigee group (median: −7.5 versus −6; ), the 1-year success rates for two groups were comparable (). Apart from urgency incontinence, women with advanced POP experienced significant resolution of irritating and obstructive symptoms after both procedures (), generating the improvement in postoperative scores of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) (). On urodynamics, only the residual urine decreased significantly following these two procedures (). Women undergoing Perigee mesh experienced significantly higher visual analogue scale (VAS) scores and vaginal extrusion rates compared with the Elevate anterior procedure (). Conclusions. With comparable success rates, the Elevate procedure has advantages over the Perigee surgery with lower extrusion rate and postoperative day 1 VAS scores. Cheng-Yu Long, Chiu-Lin Wang, Ming-Ping Wu, Chin-Hu Wu, Kun-Ling Lin, Cheng-Min Liu, Eing-Mei Tsai, and Ching-Ju Shen Copyright © 2015 Cheng-Yu Long et al. 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.