European Journal of Obstetrics & Gynecology and Reproductive Biology - Articles in Press

Pregnancy outcomes after transvaginal myomectomy by colpotomy - Uncorrected Proof

Päivi H. Rovio, Pentti K. Heinonen — 2012-02-03

Abstract: Objective: To examine long-term effects of transvaginal myomectomy by colpotomy on uterine ruptures, fertility and pregnancy outcome.Study design: Transvaginal myomectomy by colpotomy was performed for sixteen patients who had symptomatic uterine leiomyomas and wished to preserve their fertility. Data on possible pregnancies, infertility treatments, hysterectomies and other reoperations during a follow-up period of ten years were retrospectively collected from the hospital records. Those who had no outpatient contacts in the hospital records were interviewed by telephone.Results: Eight (50%) of the 16 patients tried actively to conceive and they produced 14 pregnancies: six of them had two pregnancies and two had one. The median interval between the transvaginal myomectomy and the first pregnancy was 17 months (range 14–68 months). All pregnancies were uneventful and ended in full-term delivery of a healthy infant. Uncomplicated vaginal delivery was recorded in 10 (71%), vacuum extraction in one (7%) and cesarean section in three (21%) out of 14 cases. Uterine rupture or heavy postpartal bleeding was not reported.Conclusions: Pregnancies after transvaginal myomectomy by colpotomy were uneventful and no uterine ruptures were detected during a long-term follow-up. Pregnancy rates after the procedure appear to be similar to results after abdominal or laparoscopic myomectomy. Transvaginal myomectomy by colpotomy is a safe and feasible treatment option for selected patients wishing to preserve their ability to conceive.

Postoperative lymphocysts after lymphadenectomy for gynaecological malignancies: preventive techniques and prospects - Uncorrected Proof

2012-02-02

Abstract: Postoperative lymphocyst formation is an insufficiently recognised complication of lymphadenectomy for gynaecological malignancies. Lymphocysts are collections of lymph organised into cysts that develop in contact with lymphadenectomy compartments.There has been considerable debate about the relevance of lymphocyst prevention using surgical or pharmacotherapeutic methods. Here, we review the available studies about the impact of these methods on the incidence of lymphocysts. This review suggests that several techniques may decrease the incidence of lymphocysts when used in combination. On a literature basis, the peritoneum should be left open over the lymphadenectomy sites at the end of the procedure and drains should not be placed at the end of the procedure. Omentoplasty should be encouraged and further studies are needed to assess the potential benefits of new energies. Postoperative octreotide therapy seems beneficial but the role of this drug in pelvic oncological surgery remains to be determined.

Risk factors of surgical failure following transvaginal mesh repair for the treatment of pelvic organ prolapse - Uncorrected Proof

2012-02-02

Abstract: Objective: To identify the factors associated with pelvic organ prolapse (POP) recurrence after transvaginal mesh (TVM) repair.Study design: One hundred and thirteen women with symptomatic POP stage II to IV were scheduled for TVM procedures. All subjects underwent urinalyses and pelvic examination using the POP quantification (POP-Q) staging system before and after surgery.Results: Seven (6.2%) of 113 women reported POP recurrence after a mean follow-up time of 30 months. We performed a univariate analysis of patients’ characteristics to identify the predictors of surgical failure after TVM. There was no difference between two groups as to body mass index, POP stage, mesh type, and preoperative urinary symptoms and urodynamic parameters (P>0.05). However, we found that uterine prolapse (P=0.016) and surgical experience (P=0.043) were two significant predictors of surgical failure. Multivariate logistic regression showed similar results.Conclusion: Advanced uterine prolapse and lack of surgical experience were two significant predictors of failure following TVM. POP recurrence after mesh repair appears to be unlikely beyond the learning curve.

Simple ovarian cysts in postmenopausal women: scope of conservative management - Uncorrected Proof

Madhutandra Sarkar, Mark G. Wolf — 2012-02-02

Abstract: Objective: This study was done to evaluate/investigate the natural history of simple ovarian cysts in postmenopausal women and to determine the risk for malignant transformation of these cysts.Study design: Ultrasound reports of all the postmenopausal women who attended St. Francis Hospital and Medical Center, Hartford, USA from January 1997 to April 2010 with an ultrasound diagnosis of simple cysts of ovary were reviewed retrospectively. A total of 619 patients with 743 simple ovarian cysts were evaluated. It was found that 305 out of 619 patients (49.27%) were lost in follow-up. Therefore, 314 patients (50.73%) with 378 cysts could be followed further by ultrasound study.Results: One hundred and seventy-five (46.3%) of the 378 cysts that could be followed further had spontaneous resolution and 166 cysts (43.91%) persisted unchanged over the follow-up period. Thirty cysts (7.94%) turned into complex cysts and four (1.06%) significantly increased in size. One cyst significantly decreased in size, though it did not resolve. Only one patient developed papillary serous carcinoma (high grade) of the ovary. This occurred three years after her last ultrasound for simple cyst surveillance.Conclusion: Simple ovarian cysts during the menopause can be followed conservatively because their risk for malignant transformation is low. The majority of these cysts either resolve spontaneously or persist unaltered on follow-up.

Tension-free vaginal tape-obturator in the treatment of stress urinary incontinence: a prospective study with five-year follow-up - Uncorrected Proof

Dali Cheng, Caigang Liu — 2012-02-02

Abstract: Objectives: To evaluate the medium-term outcomes of using tension-free vaginal tape-obturator (TVT-O) in the treatment of patients with stress urinary incontinence (SUI).Study design: Between December 2004 and November 2005, 103 patients with SUI were enroled and treated with TVT-O with inside-out modification. A minimum five-year follow-up (median, 65 months) was obtained from 100 patients (99.6%). Preoperative and postoperative evaluations were performed for all patients. The objective success rate of the TVT-O procedure was evaluated by a negative stress test. The secondary outcomes measured included one- and five-year subjective success rates, together with the pre- and post-operative urodynamic parameters, complications, quality of life (QOL) analysis, and patient satisfaction.Results: Among the 103 patients, 18 (17.4%) had postoperative voiding difficulties and needed urethral bladder catheterization for various periods. After the TVT-O procedure, complete disappearance of SUI occurred in 87.4% of patients, while improvement was found in about 92%. In addition, there was no difference in the cure rate between year 1 and year 5 after the procedure (P>0.05). In 90 patients, frequency and urge symptoms were significantly improved five years after the procedure (P<0.005), and maximal flow rates were decreased (P<0.05). However, the severity of obstructive symptoms and postvoid residual volumes at five years were not improved compared with one year after the procedure (P=0.10 and P=0.33 respectively). Finally, compared to pre-operation, incontinence severity degree and QOL scale scores were largely improved after the operation (P<0.001), while no difference was found between years 1 and 5 (P=0.11and P=0.09 respectively).Conclusions: Our result shows that the TVT-obturator, a novel mid-urethral sling, is a safe and effective procedure for the treatment of female SUI. Medium-term therapeutic results appear promising but further evaluation of long-term therapeutic outcomes is needed.

Is prenatal identification of fetal macrosomia useful? - Uncorrected Proof

2012-02-01

Abstract: Objectives: To determine whether prenatal identification of macrosomia (≥4000g) reduces neonatal complications and maternal perineal lesions during delivery.Study design: This historical cohort study (n=14,684 from the National perinatal database of the Audipog Association, France) included women with cephalic singleton term pregnancies. Among the babies born with macrosomia, we compared those who had been identified as such in utero (n=1211) with those who were not (n=13,473). The principal outcome was a composite variable defined as resuscitation in the delivery room, death in the delivery room or the immediate postpartum period, or transfer to a neonatal intensive care unit (NICU). The secondary outcome measures were neonatal trauma, 5-min Apgar score (≤4 and <7), and maternal perineal lesions. Results are expressed as crude relative risks and adjusted odds ratios.Results: The mean birthweight in the cohort was 4229g±219. The adjusted OR for the principal outcome defined above was 1.15 (95% CI: 0.89–1.50) in the group identified prenatally as macrosomic compared with the others (10.8% vs. 8.5%). The risk of neonatal trauma was higher in prenatally identified babies (adjusted OR: 1.80; 95% CI: 1.34–2.42). The 5-min Apgar score and the perineal lesion rate did not differ significantly between the groups. The a posteriori study power according to our results with α=0.05 was 84% (one-sided test).Conclusions: Among babies born with macrosomia, in utero identification did not improve neonatal or maternal outcomes.

Salpingectomy for ectopic pregnancy by transumbilical single-site laparoscopy with the SILS® system - Uncorrected Proof

2012-01-27

Abstract: Objective: To evaluate the feasibility in everyday practice and the advantages of salpingectomy for ectopic pregnancy by single-incision laparoscopic surgery with the SILS® system.Study design: This single-center prospective observational study included 37 women requiring salpingectomy for ectopic pregnancy who underwent single-incision laparoscopic salpingectomy with the SILS® system. Information about feasibility and intra- and post-operative data were collected. The data for these patients were compared with those of a control group of 40 women treated by standard laparoscopy.Results: Thirty-six (97%) patients were treated successfully with the SILS® system. After laparoscopic confirmation of the ectopic pregnancy, salpingectomy was performed with bipolar forceps and scissors. In one case, conversion to classic laparoscopy was performed because SILS was not feasible. Compared with the control group, operative time was longer (50±35 vs 35±30min, p=0.001) but duration of hospitalization shorter with single-site laparoscopy (1.5±1.5 vs 2.3±1.5 days, p=0.02).Conclusions: Laparoscopic salpingectomy for ectopic pregnancy appears to be feasible in everyday practice by single-incision laparoscopic surgery with the SILS® system and appears to reduce the duration of hospitalization. Larger series are necessary to confirm this conclusion.

Does single-port access (SPA) laparoscopy mean reduced pain? A retrospective cohort analysis between SPA and conventional laparoscopy - Uncorrected Proof

2012-01-27

Abstract: Objective: To compare perioperative outcomes, including pain, between single-port access (SPA) and conventional laparoscopy in patients with presumed benign gynecological adnexal diseases.Study design A retrospective cohort study was performed at Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea. All operations in each group were performed consecutively by a single surgeon.Results: A total of 188 patients were enrolled, with 94 patients per group. Baseline characteristics before surgery were similar between groups. Visual analogue scale pain scores 24h after laparoscopy were lower in the SPA group than in the conventional laparoscopy group (2, 0–7 vs. 3, 2–6 P=0.006). In addition, we found that the SPA group had less supplementary analgesic use (parenteral Ketoprofen intramuscular injection, 1 ampule=100mg) per patient after surgery compared to that in the conventional group (1 ampule, 0–7 vs. 2 ampule, 0–6, P=0.010).Conclusions: These results add to the evidence suggesting an advantage of SPA laparoscopy over conventional laparoscopy in terms of decreasing postoperative pain. Additional large, randomized controlled trials are needed to confirm these findings and to investigate long-term outcomes such as quality of life and cosmesis.

A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides - Uncorrected Proof

2012-01-27

Abstract: Objectives: Organochlorine pesticides (OCPs) and oxidative stress are reported to be associated with adverse reproductive outcomes. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous toxins including OCPs. OCPs are endocrine disrupter and prenatal exposure to them may be associated with fetal growth restriction (FGR). The objectives of the present study were (i) to determine the frequencies of polymorphic alleles of GSTM1 and GSTT1 genes in women with idiopathic FGR, (ii) to analyze the maternal and cord blood levels of the OCPs, and (iii) to identify the gene environment interaction that increases the risk of FGR.Study design: Maternal and cord blood samples of 50 FGR cases (birth weight <10 percentile for gestational age as per Lubchenco's growth chart) and equal number of normal pregnancies who were occupationally non exposed to OCPs and excluding all the known high risk factors such as anemia, hypertension, antiphospholipid antibody syndrome, medical disease, dietary habit, living style, parity, and BMI. The collected samples at the time of delivery/after delivery were analyzed for OCPs levels by gas chromatography and polymorphic analysis for GSTM1/GSTT1 gene using multiplex PCR.Results: Significantly higher levels of α,β,γ-HCH and p,p′-DDT were found in maternal blood and significantly higher levels of β and γ-HCH and p,p′-DDT were found in cord blood of FGR cases as compared to controls. The genotypic distribution of GSTM1/GSTT1 was almost similar in both the groups, but the frequency of GSTM1−/GSTT1− (null) genotype was significantly higher in FGR cases as compared to controls (p<0.05, OR=6.42). When interaction between GSTM1/GSTT1 genes polymorphism-OCPs levels and birth weight (gene–environment interaction) was ascertained, a significant association was seen between β-HCH and GSTM1− genotype with reduction in birth weight of 213g.Conclusion: Higher levels of OCPs in pregnant women may be considered as an important aetiological factor in ‘idiopathic’ FGR. GST polymorphism can influence the relationship between prenatal exposure to pesticides and FGR. The present study provides evidence that polymorphism in xenobiotic metabolising genes may modify the effect of environmental health hazards and increase the risk of FGR.

Three-year follow-up results of polypectomy with endometrial ablation in the management of endometrial polyps associated with tamoxifen in Chinese women - Uncorrected Proof

2012-01-24

Abstract: Objective: The aim of this study was to investigate the role of hysteroscopic polypectomy with endometrial ablation in the management of tamoxifen-associated endometrial polyps in postmenopausal women with a more than 3-year follow-up period.Study design: The medical records of 76 postmenopausal patients on tamoxifen who were performed hysteroscopic polypectomy with endometrial ablation were evaluated more than 3 years after the procedure with recurrence of polyps, recurrent abnormal uterine bleeding and surgical re-intervention.Results: Average follow-up period was 74.91±20.84 months. No patient underwent hysterectomy, 7 of 76 patients had a surgical re-intervention representing a total of 90.8% avoidance of additional surgery during the follow-up period, and 4 patients had a recurrent endometrial polyp representing the recurrence rate was 5.3%. 3 of 41 patients with postmenopausal bleeding had a recurrent abnormal uterine bleeding representing symptomatic relief rate is 92.7%. The treatment failed in 7 patients who requested surgical re-intervention: 4 patients requested a repeat polypectomy and ablation, 1 patient requested a repeat ablation and 2 patients requested a repeat hysteroscopy with uterine adhesion. No malignant endometrial pathological result was found.Conclusions: For postmenopausal patients suffering from endometrial polyps associated with tamoxifen, hysteroscopic polypectomy with endometrial ablation continues to be proven as a safe and effective minimally invasive treatment method. The high rate of surgical re-intervention avoidance, great symptomatic relief and low recurrence rate are very encouraging for this technology.

Uncorrected Proof

David P. van der Ham, Marjo J.G.J. van Melick, Jan G. Nijhuis, Ben Willem Mol — 2012-01-24

We thank Birkenmaier et al. for their interest in our paper, and read with interest their reaction on this subject . Indeed, their study was not included in our review, which included studies until September 2009 . We agree with the authors that there is a need for a reliable, less intrusive, cost effective and minimally invasive test to diagnose rupture of membranes. With their paper the authors have contributed to the search for a reliable diagnostic test. We also agree that further studies should evaluate the performance of the placental alpha-microglobulin-1 immunoassay (AmniSure©). However, when current RCT's on the management of PPROM confirm the findings of a recent Cochrane analysis which did not find a reduction in adverse neonatal outcome after induction of labor, one might even debate whether one needs to know whether the membranes are ruptured in equivocal cases. Expectant management would then be the most appropriate choice in all such cases.

Systematic review and meta-analysis of “inside-out” versus “outside-in” transobturator tapes in management of stress urinary incontinence in women - Uncorrected Proof

2012-01-24

Abstract: Objectives: To directly compare the current evidence for the efficacy, complications, quality of life and cost to health services of both transobturator tension free vaginal tape procedures – “inside-out” versus “outside-in” – in the surgical treatment of female stress urinary incontinence.Study design: A prospective peer-reviewed protocol was prepared a priori, and a systematic search of relevant databases from 1966 to January 2011 was performed. Meta-analyses of five randomised trials and three cohort studies were performed separately in accordance with PRISMA and MOOSE, respectively.Results: There was no significant difference in patient-reported cure/improvement (OR 1.25, 95%CI 0.78, 1.99; p=0.35) nor in objective cure/improvement (OR 1.66, 95%CI 0.8, 3.43, p=0.17) between the two groups at 12-month follow-up. Vaginal angle injuries were significantly higher with the outside-in route (OR 0.14, 95%CI 0.05, 0.41, p=0.0003). Groin/thigh pain and de-novo urgency were non-significantly higher with the inside-out route (OR 1.42, 95%CI 0.94, 2.13, p=0.10 and OR 1.46, 95%CI 0.63, 3.36, p=0.38, respectively). There was no significant difference in postoperative quality of life scores between the two groups (WMD -1.65; 95% CI -5.76, 2.46, p=0.43). None of the trials reported a “health-cost” analysis. Meta-analysis of cohort studies confirmed similar results.Conclusions: This is the first reported direct meta-analysis comparing both routes of transobturator tapes. It showed no evidence of significant differences in the efficacy and impact on women's quality of life between “inside-out” and “outside-in” transobturator tapes up to one-year follow-up. The “inside-out” route was associated with significantly fewer vaginal angle injuries but with trends towards higher risk of postoperative groin pain. Long-term follow-up of adequately powered RCTs is required to assess if these results pertain.

Glycated hemoglobin in pregnancies at increased risk for gestational diabetes mellitus - Uncorrected Proof

Johan Verhaeghe, Erik Van Herck, Katrien Benhalima, Chantal Mathieu — 2012-01-24

Abstract: Objective: The glycated hemoglobin (HbA1c) value is increasingly used for the detection of (pre)diabetes, but HbA1c decreases during pregnancy. We sought to identify clinical and metabolic correlates of HbA1c in pregnancies at increased risk for gestational diabetes mellitus (GDM).Study design: We prospectively studied 335 gravidas who received a 3-h 100g oral glucose tolerance test (OGTT) at 24–32 weeks, in most cases after an abnormal glucose challenge test. Several indices of insulin sensitivity and secretion were computed from fasting measurements and the OGTT.Results: HbA1c concentrations gradually increased in diet-treated and insulin-treated GDM gravidas compared with non-GDM gravidas. HbA1c was higher if the insulin peak was delayed until 180min compared with 60 or 120min. Stepwise regression identified the homeostasis modeling assessment of insulin resistance (HOMA-IR) as the first-rank correlate. Other correlates were ethnicity, a low insulin-to-glucose response at 60min, and gestational age. The HbA1c value corresponding to a fasting glucose of 5.1mmol/l (diagnostic of GDM) was 2mmol/mol (∼0.2%) higher if sampling occurred at 29–32 vs. 24–28 weeks or if ancestry was non-European vs. European.Conclusion: HbA1c is strongly associated with insulin resistance; in addition, HbA1c captures the first-phase insulin response. However, HbA1c varies with gestational age and ethnicity.

Gynecologists’ characteristics associated with the likelihood of performing laparoscopic-assisted hysterectomy: a nationwide population-based study - Corrected Proof

Chun-Che Huang, Ming-Ping Wu, Yu-Tung Huang — 2012-01-20

Abstract: Objective: With continuing development of minimally invasive techniques in gynecology, hysterectomy with laparoscopic assistance is increasingly performed. This study aimed to examine the relationship between the characteristics of gynecologists and the likelihood of performing laparoscopic-assisted hysterectomy (LH) under the case payment system of Taiwan's National Health Insurance.Study design: A retrospective population-based study was conducted based on the data from Taiwan's National Health Insurance Research Database. A total of 56,532 female residents aged 20 years and older who underwent total hysterectomy with or without laparoscopic assistance between 2004 and 2006 were included in the study. The gender, age and practice volume of their gynecologists were noted. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by univariate and multivariate logistic regression analyses.Results: Of the women selected, 30,478 underwent traditional total hysterectomy (TH) and 26,054 underwent LH. After controlling for clinical and nonclinical factors, male gynecologists (OR 1.65, 95% CI 1.55–1.76) were more likely to perform LH than their female colleagues. Gynecologists aged 60 years and older (OR 0.31, 95% CI 0.29–0.39) had the lowest likelihood of performing LH compared with their counterparts. In addition, surgeons with low-volume practice (OR 0.31, 95% CI 0.29–0.33) also had a significantly lower probability of performing LH compared with other surgeons.Conclusion: A higher likelihood of performing LH was observed among male and younger gynecologists with high-volume practice in Taiwan. This finding suggests that differences in practice patterns and surgical treatment decision may explain the variation in the approaches to laparoscopy-assisted hysterectomies.Condensation: Differences in practice patterns and surgical treatment decisions may explain the variation in the approaches to laparoscopic-assisted hysterectomies.

Clinicopathologic factors for central recurrence in patients with locally advanced bulky cervical cancer - Uncorrected Proof

2012-01-19

Abstract: Objective: Locally advanced bulky cervical cancer (LABCC) is characterized by poor local control. The objective of this study was to identify the clinicopathologic variables associated with one-year central-only recurrence, which will serve as criteria for adjuvant hysterectomy after radiation (AHR) in patients with LABCC.Study design: Between January 2000 and August 2007, we retrospectively evaluated outcomes in 225 patients with LABCC who were initially treated with radiation or chemoradiation.Results: Among the 225 patients with LABCC, there were 41 recurrences within one year after treatment (8 central-only and 33 pelvis and/or distant site recurrences). Age, stage, and treatment type were not associated with the one-year central-only recurrences, but tumor size≥8cm had a statistically significant association based on multivariate analysis (OR, 5.39; 95% CI, 1.15–25.31; p=0.03). The combination of non-squamous cell (non-SCC) type and tumor size≥8cm had a significantly higher rate of recurrence within one year (OR, 43.0; 95% CI, 4.78–386.68; p<0.01).Conclusions: Of patients with LABCC, those with non-SCC tumors≥8cm in size were at high risk for early central-only recurrence after cisplatin-based chemoradiation, and represent the subset of patients for whom AHR is beneficial.

Headache and adverse pregnancy outcomes: a prospective study - Corrected Proof

2012-01-19

Abstract: Objective: To investigate the association between headache, namely migraine and tension-type headache, and adverse pregnancy outcome.Study design: Prospective cohort study conducted in three tertiary care centres in Italy: 376 pregnant women suffering from headache and 326 non-headache pregnant women as controls were recruited. The diagnosis of headache was made at the beginning of pregnancy, according to the criteria of the International Classification of Headache Disorders (ICHD-II). Women were followed up until delivery, and gestational age at delivery, mode of delivery, indications for operative delivery or caesarean section, birth weight, and centile of neonatal weight at birth were carefully recorded. Main outcome measures of the study were: preterm delivery, newborns small for gestational age, and foetal losses. Odds ratios and 95% confidence intervals were calculated.Results: The incidence of preterm delivery (Adj OR, 95% CI 2.74, 1.27–5.91) was significantly higher in women suffering from headache than in controls. There was no statistically significant difference in small for gestational age newborns between the groups. Fewer women in the headache group had preterm elective caesarean section or induction of labour, than did controls, indicating a higher chance of spontaneous preterm delivery. Multivariate analysis showed that the association between headache, either migraine or tension-type, and adverse perinatal outcomes was statistically significant regardless of pre-eclampsia.Conclusions: Women with headache should be considered at risk for adverse perinatal outcomes and should, therefore, be included in a high-risk pregnancy protocol of care throughout pregnancy.

Combination of uterine artery Doppler velocimetry and maternal serum placental growth factor estimation in predicting occurrence of pre-eclampsia in early second trimester pregnancy: a prospective cohort study - Corrected Proof

Sanjib Kumar Ghosh, Shashi Raheja, Anita Tuli, Chitra Raghunandan, Sneh Agarwal — 2012-01-19

Abstract: Objective: To determine the effectiveness of the combined use of uterine artery Doppler velocimetry (UADV) and estimation of maternal serum placental growth factor (PlGF) levels in early second trimester (20–22 weeks of gestation) in identifying pregnant women at risk of developing pre-eclampsia.Study design: Prospective cohort study on 1104 pregnant women with singleton pregnancies between May 2009 and December 2010. UADV and maternal serum PlGF estimation were done at 20–22 weeks’ gestation. Association between the two variables and the occurrence of pre-eclampsia was analyzed by logistic regression analysis and odds ratio was computed. The results were considered significant when p was <0.05.Results: Logistic regression analysis showed that both abnormal UADV (odds ratio (OR) 4.1; 95% CI 2.3–7.2; p=0.000) and serum PlGF<188pg/ml (OR 3.6; 95% CI 1.95–6.5; p=0.000) are independent variables in the occurrence of pre-eclampsia, and the difference between the association of these two variables with pre-eclampsia was statistically insignificant as 95% CI values overlap. Multivariate logistic regression analysis showed that a combination of abnormal UADV and serum PlGF<188pg/ml at 20–22 weeks had a very poor association (OR 1.1; 95% CI 0.3–3.8; p=0.938) with the occurrence of pre-eclampsia, as the 95% CI values encompass 1 and p is >0.05.Conclusion: UADV and maternal serum PlGF estimation at 20–22 weeks of gestation are strong predictors of the occurrence of pre-eclampsia when used individually but in combination their association with pre-eclampsia is not significant.

Severely decreased activity of placental dimethylarginine dimethylaminohydrolase in pre-eclampsia - Corrected Proof

2012-01-19

Abstract: Objectives: Asymmetric dimethylarginine (ADMA) is a key regulator of nitric oxide production. Elevations of ADMA have previously been associated with endothelial dysfunction in pre-eclamptic women. ADMA is degraded mainly by dimethylarginine dimethylaminohydrolase (DDAH), which is also expressed in placental tissue. Therefore, we measured placental DDAH expression and activity in pre-eclampsia and normal pregnancies in order to determine whether impairment of this enzyme in the pre-eclamptic placenta could contribute to elevations of ADMA levels in these women.Study design: ADMA plasma levels were measured by LC–MS/MS in 18 pre-eclamptic patients and 28 controls. Placental DDAH activity was determined by measuring the degradation of [2H6]-labeled ADMA in tissue homogenates from placental biopsies in 15 women with pre-eclampsia and 16 controls. Placental mRNA expression of DDAH 1, DDAH 2, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and protein-arginine methyltransferase 1 (PRMT1) was determined in tissue biopsies by RT-PCR.Results: Placental DDAH activity was almost undetectable in pre-eclampsia, and it was significantly higher in controls. ADMA plasma levels were higher in pre-eclampsia as compared to normal pregnancies (0.51±0.15μmol/l vs. 0.42±0.07μmol/l; p=0.005), and the difference between maternal and fetal ADMA levels (feto-maternal ADMA gradient) was lower in pre-eclampsia (0.63±0.20μmol/l vs. 0.80±0.18μmol/l; p=0.02). Furthermore, mRNA expression levels of DDAH 2 were significantly lower in pre-eclamptic women (p=0.04), while PRMT1 expression levels were the same. In pre-eclampsia, we found only weak correlations between maternal ADMA levels and DDAH 1 (r=−0.41; p=0.22) and DDAH 2 expressions (r=−0.45; p=0.17) but a slightly stronger correlation between DDAH 2 expression and feto-maternal ADMA gradient (r=0.60; p=0.07).Conclusion: Decreased DDAH activity in the pre-eclamptic placenta might contribute to elevated ADMA levels in these patients.

LETTER TO THE EDITOR—CORRESPONDENCE to Authors’ Response - Corrected Proof

Amita Mahendru, Christoph Lees — 2012-01-18

We would like to thank Professor Joachim Dudenhausen for his comments . Ours is an Opinion article and our objective is not to answer the question but to appraise the existing evidence regarding use of FBS as a gold standard diagnostic technique for foetal distress and its role in reducing caesarean section.

Authors’ response - Corrected Proof

Marcello Ceccaroni, Giovanni Roviglione, Roberto Clarizia — 2012-01-18

We appreciated the interesting comments of Uccella et al. about our paper . As previously stated, different aspects can play a role in the genesis of vaginal cuff dehiscence, such as vault infections, wound hematoma, resumption of sexual activity before complete healing, advanced age, previous radiation therapy, chronic steroid administration and trauma . Uccella et al. underlined that the route by which colporrhaphy is performed represents an important factor influencing the risk of dehiscence. In a retrospective review, the authors reported that laparoscopic and robotic vault sutures showed a higher risk of dehiscence when compared with the trans-vaginal approach . Moreover, in this series, the vaginal route not only seemed to allow better results but also was shown to be an easier procedure compared with laparoscopic colporrhaphy.

The 2004 Italian legislation on the application of assisted reproductive technology: epilogue - Corrected Proof

2012-01-18

Abstract: Objective: To evaluate how the unique Italian fertility regulations (≤3 inseminated oocytes/cycle, transfer of all embryos, prohibition of embryo cryopreservation) affected outcomes of ART.Study design: Case–control study from the Center of Reproductive Medicine, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. We compared outcomes of ART patients between five years before (n=1791) and five years after (n=2474) the implementation of the law.Results: The mean embryo transfer (ET) rate was 3.1±2.1 and 1.7±1.1 before and after the law. Significantly more ICSI procedures were performed in women above 35 years old during the post-law period. The ET rate was higher before (88.6%) than after (80.5%) the law (OR 1.9, 95% CI 1.6, 2.2) especially in women >37 years undergoing ICSI (88.2 vs. 76.1%; OR 2.3, 95% CI 1.3, 4.2). The clinical pregnancy rates were practically unchanged but the proportion of triplet births significantly decreased after the law (10.3 vs. 4.1%, OR 2.7, 95% CI 1.4, 5.0).Conclusion: In contrast to interim analyses, we found that the statutory obligation to transfer all available embryos produced from up to three inseminated oocytes reduced the ET rates, especially in older women, and decreased the triplet births rate.

Positive reproductive family history for spontaneous abortion: predictor for recurrent miscarriage in young couples - Corrected Proof

Silvana Miskovic, Vida Culic, Pasko Konjevoda, Jasminka Pavelic — 2012-01-17

Abstract: Objective: The etiology of recurrent spontaneous abortions (RSA) in chromosomally normal parents is still unexplained. It is unclear whether or not some factors, such as spontaneous abortions (SA), which occur among extended family members can create a predisposition to RSA. Therefore, this study comprises two parts: (a) an epidemiological part, to evaluate the relationship between RSA in 567 couples and the frequency of SA among their first (I), second (II) and third (III) generation relatives, and (b) a genetic part, investigating whether parental and fetal chromosomal status may predispose to the occurrence of RSA.Study design: Couples (567) having one or more SA were analyzed in this retrospective case-control study. The family reproductive history data was collected from their medical charts.Results: The total number of SA found in 567 couples was 1174, and the largest number occurred at 8–10 weeks of gestation. The majority of spouses had normal karyotypes (88.5% and 91%). Of the remainder, 65% of females and 76% of males expressed constitutional chromosomal variation, mostly pericentric inversion of chromosome 9. Cytogenetic analysis of aborted material showed some type of change in 40% of cases. The family reproductive history data indicated that SA among the couples’ I, II and III generation relatives happened with a frequency two to three times higher than that of the general population (55.5, 47.6 and 32.6% for female relatives, and 45.8, 44.1 and 15.1% for male relatives).Conclusion: Positive reproductive family history for SA might be the causal factor for RSA and can also predetermine women that are of greater susceptibility to preterm pregnancy.

Uterine necrosis and pyometra following surgical hemostatic Cho suture for postpartum haemorrhage: two cases - Corrected Proof

Stéphane Ploteau, Mathilde Renou, Patrice Lopes — 2012-01-10

We report two cases of uterine necrosis and pyometra after surgical haemostatic Cho suture for postpartum haemorrhage. A healthy 23-year-old primipara presented with severe postpartum haemorrhage immediately after a uterine inversion following vaginal delivery at 41 weeks. The pregnancy had been normal with no history of clinical intraamniotic infection. No satisfactory response was obtained after manual repositioning of the uterus and medical treatment by intravenous oxytocin and sulprostone. The patient therefore underwent surgery with bilateral uterine artery ligation and Cho compressive uterine sutures. Haemostasis was obtained after these procedures. In the post-operative period she made a good recovery but was treated by amoxicillin and clavulanic acid for pyrexia, an elevated C reactive protein and leucocytosis.

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates - Corrected Proof

2012-01-09

Abstract: Objective: To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11–13 weeks’ gestation in the prediction of small-for-gestational age (SGA) neonates.Study design: Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls.Results: In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4–93.4ng/mL vs 94.9, IQR 56.7–131.2ng/mL, p=0.002) and IGFBP-1 (58.2, IGR 39.8–84.9ng/mL vs 81.4, IGR 57.3–105.5ng/mL, p=0.002) but not IGFBP-3 (54.5, IGR 45.6–61.5ng/mL vs 55.4, IGR 47.4–64.9ng/mL, p=0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA.Conclusion: Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.

Adoptive transfer of CD4+CD25+ regulatory T cells for prevention and treatment of spontaneous abortion - Corrected Proof

Yongxiang Yin, Xiaofeng Han, Qin Shi, Yiming Zhao, Yang He — 2012-01-09

Abstract: Objectives: The purpose of this study was to examine whether adoptive transfer with in vitro expanded CD4+CD25+ regulatory T cells (Tregs) could prevent immune response-mediated spontaneous abortion in mice.Study design: Female CBA/J mice were mated with male Balb/c as the control with normal pregnancy or with DBA/2J mice as a model of spontaneous abortion. The CBA/J mice mated with DBA/2J were treated intravenously with freshly isolated or in vitro expanded Tregs on day 1 or 4 of pregnancy, respectively. The numbers of surviving and reabsorbed fetuses in the different groups of mice were counted on day 14 of pregnancy, and the concentrations of cytokines in individual sera and the supernatants of cultured Tregs were measured by ELISA.Results: Adoptive transfer with freshly isolated Tregs only slightly reduced the fetal resorption rate, which was not significantly different from that of the mice without Treg treatment, regardless of treatment at early stage and implementation of pregnancy. In contrast, adoptive transfer with in vitro expanded Tregs significantly reduced the fetal resorption rates, particularly for treatment at early stage of pregnancy (P<0.05). Furthermore, adoptive transfer with in vitro expanded Tregs at early stage of pregnancy significantly increased the levels of serum IL-10, TGF-β1, and the ratios of IL-10 to IFN-γ.Conclusions: Our data clearly indicated that adoptive transfer with in vitro expanded Tregs at early stage of pregnancy protected fetuses from spontaneous abortion by re-establishing immune tolerance in mice.

Early non-invasive detection of fetal Y chromosome sequences in maternal plasma using multiplex PCR - Corrected Proof

2012-01-09

Abstract: Objective: Clinical indications for fetal sex determination include risk of X-linked disorders, a family history of conditions associated with ambiguous development of the external genitalia, and some fetal ultrasound findings. It is usually performed in the first trimester from fetal material obtained through CVS and is associated with an approximately 1% risk of miscarriage. Ultrasound fetal sex determination is often performed after 11 weeks of gestation. This study aims to validate a reliable method for non-invasive prenatal diagnosis of fetal gender using maternal plasma cell-free fetal DNA (cffDNA) for fetal sex assessment in the first trimester of pregnancy and test its clinical utility in the diagnosis of potentially affected pregnancies in carriers of X-linked disorders.Study design: In the validation study, blood samples from 100 pregnant women at 6–11 weeks of gestation were analysed. In the clinical study, 17 pregnancies at risk of having an affected fetus were tested. 7ml of maternal blood in EDTA were obtained and cffDNA was extracted using a commercially available kit. DNA was enzymatically digested using a methylation sensitive endonuclease (AciI) to remove maternal unmethylated sequences of the RASSF1A gene. A multiplex PCR was performed for the simultaneous amplification of target sequences of SRY and DYS14 from chromosome Y, along with RASSF1A and ACTB sequences. Amplification of these loci indicates fetal gender, confirms the presence of cffDNA and allows assessment of digestion efficiency.Results: After establishing the appropriate experimental conditions, validation studies were successful in all 100 cases tested with no false negative or false positive results. Y chromosome-specific sequences were detected in 68 samples, and 32 cases were diagnosed as female based on the amplification of RASFF1A sequences only, in the absence of ACTB. In the clinical studies, fetal sex was correctly diagnosed in 16 pregnancies, and one case was reported as inconclusive.Conclusions: Fetal sex assessment by detecting Y chromosome sequences in maternal blood can be routinely used from the 6th week of gestation. Reliable fetal sex determination from maternal blood in the 1st trimester of gestation can avoid conventional invasive methods of prenatal diagnosis.

Interleukin 18 messenger RNA and proIL-18 protein expression in chorioamniotic membranes from pregnant women with preterm prelabor rupture of membranes - Corrected Proof

2012-01-09

Abstract: Objective: To quantify the expression of IL-18 mRNA and protein in the chorioamniotic membranes of pregnant women with PPROM and correlate expression with histological chorioamnionitis.Study design: A case control study that included 42 pregnant women not in labor in the following groups: PPROM (n=28) and controls with intact membranes submitted to selective cesarean section at term (n=14). Expression of IL-18 mRNA in chorioamniotic membranes was determined by real-time polymerase chain reaction, and IL-18 protein expression was measured by western blot. Histopathological analyses and immunolocalization of IL-18 by immunohistochemistry were also performed. Analyses were performed using the Mann–Whitney or Fisher's exact tests and the group effect was considered significant if the adjusted p-values were <0.05 and the magnitude of change was greater than 2-fold for mRNA expression.Results: IL-18 mRNA was present in 100% of samples and no difference in expression was observed between term vs. PPROM membranes (fold-change 0.12; p=0.88). In the PPROM group, no difference was observed in IL-18 mRNA regarding gestational age (fold-change 0.11; p=0.42) or the presence of histological chorioamnionitis (fold-change 0.26; p=0.15). ProIL-18 was present in all samples. IL-18 was immunolocalized to amnion, chorion and decidua cells, with intense immunohistochemical staining at the choriodecidual junction.Conclusion: Chorioamniotic membranes are sources of IL-18 mRNA and proIL-18, and their expression is unrelated to PPROM or histological chorioamnionitis.

Comparison study of single-port (Octoport™) and four-port total laparoscopic hysterectomy - Corrected Proof

Tong Wang, Gun Oh Chong, Nae Yoon Park, Dae Gy Hong, Yoon Soon Lee — 2012-01-09

Abstract: Objective: To compare the perioperative surgical outcomes and complication rates between single-port total laparoscopic hysterectomy and conventional four-port total laparoscopic hysterectomy.Study design: Between June 2009 and April 2011, 56 patients underwent total laparoscopic hysterectomy. Of these 56 patients, 28 underwent single-port (Octoport™) total laparoscopic hysterectomy and 28 underwent conventional four-port total laparoscopic hysterectomy. We analyzed the following parameters for all the patients: age, body mass index, operative time, blood loss, change in hemoglobin level, vaginal stump suture time and length of hospital stay.Results: The general characteristics of the patients were similar in both groups. There were no statistically significant differences in blood loss, hemoglobin change, length of postoperative hospital stay and complication rate. However, the mean operative time of the single-port group was significantly longer than that of the four-port group (93.5±24.0min vs. 78.7±17.4min; P=0.011). The operative time for vaginal stump suture was profoundly decreased with experience in the single-port group.Conclusion: With the exception of operative time, the surgical outcomes and incidence of complications of the single-port group were comparable to those of the four-port group. However, the operative time decreased in the single-port group with increasing experience.

Vacuum-assisted closure therapy in the management of patients undergoing vulvectomy - Corrected Proof

2012-01-06

Abstract: Objectives: To investigate whether systematic postoperative VAC therapy could improve vulvectomy healing.Study design: We reviewed medical data from 54 women who underwent in the period of March 2006 to December 2009 radical vulvectomy or wide local vulvectomy with defect volume >40cm3. Patients were divided into two groups according to immediate postoperative care. Patients treated with systematic vacuum-assisted closure (VAC) therapy immediately after surgery were included in the “VAC group” while patients receiving conventional care (CC) were included in the “CC group”.Results: The characteristics of the VAC group (n=30) and CC group (n=24) were similar and there were no significant differences in operative data, histological results or oncologic follow-up. The median length of use of VAC was 11 days after surgery (6–38). The length of hospital stay for patients in the VAC group and CC group was 17.8 (±8.7) and 18.4 days (±9.9) (p=0.8) respectively. The lengths of complete healing were 44.4 (±18.4) vs. 60.2 (±28.7) days (p=0.0175) respectively.Conclusions: In our study we proved that using VAC dressing immediately after vulvectomy (at least 6cm×7cm) for 11 days reduces the total length of cicatrization by approximately 16 days.

Treatment of uterine myoma with 5 or 10mg mifepristone daily during 6 months, post-treatment evolution over 12 months: double-blind randomised clinical trial - Corrected Proof

2012-01-06

Abstract: Objectives: To evaluate the efficacy and safety of 5 and 10mg doses of mifepristone for 6 months for the treatment of uterine fibroids and to check those results at 1 year post-treatment.Study design: Randomised double-blind clinical study carried out at the “Eusebio Hernández” Hospital, Havana, Cuba. One hundred and seventy-six women with symptomatic uterine fibroids received one daily capsule of 10mg mifepristone orally or one daily capsule of 5mg mifepristone orally, over 6 months. Up to two endometrial biopsies were performed. Reduction in fibroid volume was used to evaluate efficacy.Results: The 5 and 10mg dose had a similar efficacy in reducing the fibroid volume, 48.1% and 39.1%, p=0.07, and that of the uterus, 30.3% and 27.2%, p=0.63, respectively. Twelve months after treatment the majority of the subjects were asymptomatic with symptom prevalence similar to that at the end of treatment, except for hypermenorrhea and metrorrhagia, although the intensity of hypermenorrhea was much less, p<0.01.Conclusions: (1) Both doses obtain similar results in reducing fibroid size. (2) Administering 6 months’ treatment achieves symptomatic improvement lasting 1 year in a high percentage of cases. (3) More studies need to be carried out with longer treatment and follow-up periods.

Experience of the Hungarian Preconception Service between 1984 and 2010 - Corrected Proof

A.E. Czeizel — 2012-01-06

Abstract: The objective of this historical account is to summarize the concept, objectives, methods, results and general experience of the Hungarian Preconception Service, Budapest, based on 27 years (1984–2010) and 25,313 women and couples. The service includes counseling and care (examinations and medical interventions) based on three steps: (1) preconception screening for reproductive risk factors (“reproductive health check-up”), (2) a 3-month preparation for conception, because conception is when some major developmental events, such as the sex of the conceptus and the foundation of health and many diseases, are determined, and (3) achievement of optimal conception and better protection of the embryo in early pregnancy. With normal prenatal care, pregnant women visit clinics between the 7th and 12th gestational weeks, but the embryo has passed through his/her most vulnerable period before the 10th week, and thus prenatal care is too late to reduce the risk of congenital abnormalities. The new primary health care infrastructure for preconception care is performed by qualified and trained nurses and midwifes. Couples at risk are selected and are referred to specialists who can reject or confirm the supposed risks and treat the couples if necessary as part of their secondary health care. The most important results of the Hungarian preconception service were (i) a significant reduction in the rate of preterm births (5.0% vs. 9.2%) which has been linked mainly to preconception screening of sexually transmitted infections of female participants followed by appropriate treatment, (ii) a very significant reduction of congenital abnormalities (2.9% vs. 4.0%), particularly neural-tube defects and cardiovascular malformations, due to periconception multivitamin supplementation, (iii) reduction of smoking among female participants, (iv) involvement of male partners in the family planning health system, (v) much improved identification of couples at high risk and greater access to the secondary care of specialists. In conclusion, the Hungarian experience demonstrates the feasibility and usefulness of preconception care in the prevention of adverse birth outcomes including congenital abnormalities and preterm births.

Gene expression patterns of the 11β-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism - Corrected Proof

2012-01-05

Abstract: Objective: To assess 11-β-hydroxysteroid dehydrogenase 2 (11β-HSD2) gene expression patterns in human placental samples from intrauterine growth restriction (IUGR) pregnancies using normal pregnancy as control.Study design: We compared 11-β-HSD2 gene expression in placental samples from all IUGR pregnancies treated in our clinic between January 1, 2010 and January 1, 2011 vs. 140 normal pregnancy samples from the same study period. Clinical characteristics were also assessed and compared between the IUGR and normal pregnancy groups.Results: Mean gestational weight gain in the IUGR group was significantly lower than in the control group. Similarly, change in body mass index (BMI) was lower. Impending intrauterine fetal asphyxia was significantly more common in the IUGR group. The 11β-HSD2 gene was underexpressed compared to controls, but this underexpression was only observed after the 33rd gestational week. Within the IUGR group, in cases of impending intrauterine fetal asphyxia the 11β-HSD2 gene was underexpressed compared to both impending asphyxia in non-IUGR cases, or IUGR without impending asphyxia.Conclusion: Low gestational weight gain appears to predict IUGR. The 11β-HSD2 gene in IUGR is underexpressed and may result in an impaired placental barrier, decreasing protection against maternal glucocorticoids, which are thought to be prominent in fetal programming. Maternal glucocorticoid exposure resulting from an impaired placental barrier may increase the risk for cardiovascular and metobolic disorders later in adult life. In IUGR, before the 33rd gestational week, the expression of the 11β-HSD2 gene remains physiological. The underexpression of this gene after the 33rd week in impending intrauterine fetal asphyxia in IUGR points to an increased sensitivity to hypoxia when impending asphyxia is present in the late phase of IUGR pregnancies.

Interstitial cystitis: diagnosis and management - Uncorrected Proof

Monika Vij, Sushma Srikrishna, Linda Cardozo — 2012-01-05

Abstract: Interstitial cystitis/painful bladder syndrome is a chronic condition that causes debilitating bladder pain which can be associated with urgency, frequency and nocturia. Its cause is not clear and it is still a disease diagnosed by exclusion. Oral or intravesical therapies are the main stay of treatment whilst surgical procedures are reserved for refractory cases. This condition usually warrants a multidisciplinary approach for optimum outcome. This article gives an overview of the changes in definition, aetiopathogenesis and available treatments.

ADIPOQ gene polymorphisms and susceptibility to polycystic ovary syndrome: a HuGE survey and meta-analysis - Corrected Proof

Lei Xian, Wenwu He, Feng Pang, Yanling Hu — 2012-01-05

Abstract: Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders. The aim of this study was to investigate possible associations between 45T/G and 276G/T variants of the ADIPOQ gene and susceptibility to PCOS. A meta-analysis of 11 published case–control studies on the 45T/G variant of the ADIPOQ gene (involving a total of 1176 patients with PCOS and 1759 controls) and eight published case–control studies on the 276G/T variant of the ADIPOQ gene (involving a total of 895 patients with PCOS and 1024 controls) was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The comparison of G vs. T in ADIPOQ 45T/G showed significant differential susceptibility to PCOS (OR=1.397, 95% CI 1.156–1.689). A significant association was also found between PCOS susceptibility and the comparison of G vs. T in ADIPOQ 276G/T (OR 0.812, 95% CI 0.704–0.937). However, protective effects were found in both sites under the co-dominant model for Caucasians. Further studies are warranted to assess these associations in greater detail, especially in Asian populations.

l-Arginine pathway in neonates with meconium-stained amniotic fluid - Corrected Proof

Ozlem Gun Eryilmaz, F. Nur Aksakal, Nedim Cicek, Elif Gul Eyi, Aslihan Avci — 2012-01-05

Abstract: Objective: To study the arginase, nitric oxide synthase and nitric oxide pathways associated with passage of meconium.Study design: Cord blood samples were collected from 20 newborns with meconium-stained amniotic fluid (MSAF) and from 23 newborns with clear amniotic fluid. Cord blood pH, arginase, nitric oxide synthase and nitric oxide levels were compared between the groups.Result: The differences between the arginase and nitric oxide measurements of the newborns with MSAF and those with clear amniotic fluid were significant. In the MSAF group arginase levels were significantly lower (p=0.007) and nitric oxide levels were significantly higher (p=0.032) than the clear amniotic fluid group.Conclusion: Hypoxia may be involved in the pathogenesis of meconium passage due to decreased arginase and increased nitric oxide levels.

Three-year outcome of transvaginal mesh repair for the treatment of pelvic organ prolapse - Corrected Proof

2012-01-03

Abstract: Objective: To evaluate the clinical and urodynamic outcomes of transvaginal mesh repair (TVM) for the treatment of pelvic organ prolapse (POP).Study design: One hundred and twenty-four women with POP stage II to IV were scheduled for a TVM procedure. Preoperative and postoperative assessments included pelvic examination, urodynamic testing, and a personal interview about urinary symptoms using a standard questionnaire.Results: We found a significant improvement at points Aa, Ba, C, Ap, and Bp (P<0.001) except for total vaginal length (P=0.08), and the overall success rate was 93.5% (116/124). Various urinary symptoms improved significantly following TVM (P<0.01). In addition, residual urine, functional urethral length, and the rate of detrusor overactivity, improved significantly after surgery (P<0.05). Apart from vaginal erosion (14/124; 11.3%), the rates of other surgical complications were acceptably low.Conclusion: TVM is an effective procedure for the treatment of POP and urinary symptoms, this being possibly related to postoperative release of urethral obstruction. Vaginal erosion is less likely to occur beyond the learning curve.

Poland syndrome with Mullerian agenesis: a rare occurrence - Corrected Proof

Shalini Rajaram, Sumita Mehta, Bindiya Gupta, Vineeta Rathi, Neerja Goel — 2012-01-03

A young girl, 20years old, presented with complaints of unequal breast development, primary amenorrhea and deformity of the right hand. She had no history of cyclical abdominal pain, nipple discharge, other limb deformities, or visual or hearing problems. Her mother and two sisters were normal and had attained normal menses. On examination her height was 157.5cm and weight 55kg. The chest was asymmetrical with depression in the bony cage on the right upper side, indicating absent pectoralis major muscle, and with an underdeveloped right breast, but there was no bony involvement. Claw hand deformity was present in the right hand (). Dorsally the right scapula was less prominent than the left. Axillary hair was also absent on the right side. On auscultation the apex beat was present in the 5th right intercostal space. Examination of the eyes, ears, nose, facial symmetry, palate, and dentition was normal. Pubic hair was Tanner's stage 3 and external genitalia were normal. There was a blind vagina 3cm in length and rectal examination revealed that the uterus was absent.

Expression and possible role of interleukin-10 receptors in patients with adenomyosis - Corrected Proof

Xiaoyan Qin, Hualing Zhang, Fei Wang, Jing Xue, Zeqing Wen — 2012-01-03

Abstract: Objective: To investigate the expression and potential roles of interleukin-10 receptor 1 (IL-10R1) and interleukin-10 receptor 2 (IL-10R2) in adenomyosis.Study design: This prospective study examined 33 women with histologically proven adenomyosis and 21 women without adenomyosis who had undergone hysterectomy for non-endometrial pathology. Comparative immunohistochemistry was used to evaluate the expression and localization of IL-10R1 and IL-10R2. Tissue sections were immunostained with goat anti-human interleukin-10 receptor alpha and rabbit anti-human interleukin-10 receptor beta antibodies. The presence and localization of IL-10R1 and IL-10R2 were evaluated microscopically throughout the menstrual cycle in eutopic and ectopic endometrial tissues of women with adenomyosis, and the results were compared with those for normal endometrium.Results: IL-10R1 and IL-10R2 were mainly expressed by epithelial cells in both women with adenomyosis and controls. Epithelial expression of IL-10R1 and IL-10R2 was higher in adenomyotic samples than in eutopic endometrium of women with adenomyosis or normal endometrium. Moreover, epithelial expression of IL-10R1 was higher in eutopic endometrium of women with adenomyosis than in normal endometrium. Epithelial expression of IL-10R1 showed cyclic variation in eutopic endometrium of women with adenomyosis and normal endometrium, with elevated expression in secretory-phase tissues compared with proliferative-phase tissues.Conclusions: Intrinsic abnormalities concerning IL-10 and IL-10 receptors may be present in eutopic and ectopic endometria of women with adenomyosis. These findings suggest that IL-10 receptors may be involved in the immunotolerant and/or anti-inflammatory process of adenomyosis.

Relationship of serum adipocyte-derived proteins with insulin sensitivity and reproductive features in pre-pubertal and pubertal daughters of polycystic ovary syndrome women - Corrected Proof

2012-01-03

Abstract: Objective: To evaluate in a cross-sectional study adiponectin and leptin levels in prepubertal and pubertal daughters of women with PCOS and their relationship to insulin sensitivity and reproductive features.Study design: We studied 92 daughters of PCOS women (PCOSd) and 76 daughters of control women (Cd) matched by age and body mass index SD scores and distributed according to breast Tanner stage: prepuberty (Tanner 1), early puberty (Tanner 2–3) or late puberty (Tanner 4–5). In all girls an oral glucose tolerance test was performed. Leptin, adiponectin, sex steroids, SHBG, glucose, insulin and lipid profile were determined. Leptin–adiponectin ratio, free androgen index and insulin sensitivity (HOMA-IR and ISI composite) were then calculated.Results: Prepubertal PCOSd showed lower serum adiponectin compared to Cd (p=0.028), whereas during puberty no differences were observed between the groups. Leptin concentrations were similar in both groups in all Tanner stages. In addition, in PCOSd during early puberty, adiponectin showed a negative correlation with testosterone and leptin showed a negative correlation with ISI composite, which were independent of BMI SDS (r=−0.39; p=0.02 and r=−0.42; p=0.01).Conclusion: These observations suggest that during the prepubertal period PCOSd exhibit abnormal adiponectin levels, independently of BMI. Moreover, leptin and adiponectin may be related to metabolic and reproductive abnormalities observed in PCOSd during the early stages of sexual development.

Association of IL-18 genotype with impaired glucose regulation in Korean women with polycystic ovary syndrome - Corrected Proof

Ji Won Kim, Min Ho Lee, Ji Eun Park, Tae Ki Yoon, Woo Sik Lee, Sung Han Shim — 2011-12-29

Abstract: Objective: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. The pro-inflammatory cytokine, interleukin (IL)-18, is associated with metabolic syndrome, and elevated serum IL-18 levels are related to obesity and insulin resistance in PCOS patients. However, the role of IL-18 in the PCOS remains unclear. So we examined whether or not two functional polymorphisms in the IL-18 gene, −137G>C and +183A>G, are associated with PCOS itself or glucose intolerance in Korean women with PCOS.Study design: The IL-18 genotypes of 126 women with PCOS and 113 controls were determined and their serum levels of lipid and hormone profiles measured. The insulin resistance index was calculated from the glucose and insulin concentrations obtained by oral glucose tolerance tests.Results: There were no statistically significant differences in the distribution of −137 G>C polymorphisms among the women classified according to presence or absence of PCOS and obesity. However, the −137G/G allele was more frequent in the PCOS+impaired glucose regulation (IGR) group than PCOS+normal glucose tolerance group (X2=7.637, pBonf=0.022). The PCOS group with only the −137G allele had a significantly increased risk of IGR compared to the PCOS group with the −137C allele (92 vs. 8%, odds ratio=6.325, 95% confidence interval=1.403–28.519). In the PCOS patients, the mean fasting and 2-h post-prandial plasma glucose level of patients with only the −137G allele was significantly higher than those of the patients with the −137C allele (88.87±9.49 vs. 84.37±6.19, p=0.002 and 120.07±34.53 vs. 107.54±27.13, p=0.038). Only one woman was heterozygous for the +183A>G polymorphism and the other 224 subjects were homozygous for the polymorphism (A/A).Conclusion: The IL-18 −137G allele could play a role in the predisposition to glucose intolerance in Korean women with PCOS, and the +183G allele of IL-18 is not associated with the Korean population.

The role of primary physicians in the diagnostic delay of lower urinary tract and pelvic organ prolapse symptoms - Corrected Proof

Haim Krissi, Ram Eitan, Yoav Peled — 2011-12-21

Abstract: Objective: To explore the role of primary physicians in the diagnostic delay of lower urinary tract and pelvic organ prolapse symptoms in parous women.Study design: Prospective cohort study of women referred to the Urogynecology Outpatient Clinic of a major medical center by primary physicians in the community for initial assessment of lower urinary tract and pelvic organ prolapse symptoms.Results: Most of the women blamed themselves for the delay. However, the primary physicians were considered responsible for 33.5% of the delays. There was no between-group differences in self-blame (p=0.438). Women with pelvic organ prolapse blamed the gynecologist significantly more often than women with lower urinary tract symptoms (p=0.043); 38.6% of the physicians considered the symptoms not sufficiently severe or a natural part of aging.Conclusion: Patients need to receive more information on the availability of specific evaluations and treatments for pelvic floor dysfunction.

Herpes simplex virus type 1 is the main cause of genital herpes in women of Natal, Brazil - Uncorrected Proof

2011-12-21

Abstract: Objectives: The purpose of this study was to assess the prevalence of HSV-1 and HSV-2 in sexually active women who participated in the cervical cancer screening program in Natal, Brazil.Study design: The study included 261 sexually active women resident in the metropolitan area of Natal, Brazil and attending a public clinic for cervical screening. From each participant, a sample of exfoliated uterine cervical cells was collected, using a cytobrush which was conditioned in a tube containing a preserving solution (PBS+vancomycin+nystatin) and sent to a laboratory where it was processed for DNA extraction. The samples were analyzed for the presence of HSV-1 and HSV-2 DNA in separate reactions by PCRs using specific primers.Results: HSV-1 in genital infection is four times more prevalent than HSV-2 in the population analyzed. The highest prevalence rates for both viruses were found in women aged 31–39years. We did not observe any association between the presence of both virus serotypes and socio-demographic characteristics in the population studied, nor with some classical risk factors for sexually transmitted diseases.Conclusions: HSV-1 was the major cause of genital infection by Herpes simplex virus in the women included in this study. No association was found between HSV infection and the socio-demographic characteristics or some classical risk factors for sexually transmitted diseases.

Metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 are increased in vulvar lichen sclerosus - Corrected Proof

2011-12-19

Abstract: Objectives: To evaluate the expression of different matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in vulvar lichen sclerosus (LS), a chronic dermatosis in women, histologically characterized by a zone of collagen remodeling in the superior dermis.Study design: Analysis of the expression of different MMPs (MMP-1, -2, -9 and -13) and TIMPs (TIMP-1 and -2) by reverse transcriptase-polymerase chain reaction (RT-PCR) in vulvar biopsies from patients with LS (n=11), classified according to Hewitt histological criteria and compared with clinically normal vulvar tissue (n=5), and the immunohistochemistry of MMP-2 and -9 and TIMP-1 and -2 distribution in the remodeling zone of LS (n=31) and in clinically normal vulvar tissue (n=28).Results: Although no statistically significant difference between LS and normal skin groups at the mRNA level of MMP and TIMP transcripts was shown, an increase in the immunodistribution of MMP-2 and -9 and TIMP-1 and -2 in LS compared to normal vulvar skin was observed.Conclusions: These results suggest that these molecules could be related to the process of cutaneous collagen remodeling in LS pathology.

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer - Corrected Proof

2011-12-19

Abstract: Objective: To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET).Study design: Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts. Outcome measures were gestational age at delivery, birth weight, birth length, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA) infants, perinatal mortality and minor/major birth defects (evaluated by parent questionnaire).Results: Gestational age (38.6±2 versus 38.7±1.9 weeks) and preterm delivery rate (6.9% versus 6.9%, aOR: 0.96 95%CI: 0.76–1.22) in singletons born after the transfer of vitrified embryos were comparable to those born after the transfer of fresh embryos. Children born after the transfer of vitrified embryos had a higher birth weight (3028±465 versus 2943±470g, p<0.0001) and lower LBW (8.5% versus 11.9%, aOR: 0.65 95%CI: 0.53–0.79) and SGA (3.6% versus 7.6% aOR: 0.43 95%CI: 0.33–0.56) rates. Total birth defect rates (including minor anomalies) (2.4% versus 1.9%, aOR: 1.41 95%CI: 0.96–2.10) and perinatal mortality rates (0.6% versus 0.5%, aOR: 1.02 95%CI: 0.21–4.85) were comparable between the vitrified and fresh groups.Conclusions: Vitrification of embryos/blastocysts did not increase the incidence of adverse neonatal outcomes or birth defects following single embryo transfer.

Three-dimensional volume off-line analysis as compared to real-time ultrasound for assessing adnexal masses - Corrected Proof

2011-12-16

Abstract: Objective: To assess the agreement between three-dimensional volume off-line analysis as compared to real-time ultrasound for assessing adnexal masses.Study design: Ninety-nine non-consecutive women diagnosed as having an adnexal mass were assessed by transvaginal power Doppler ultrasound. One single examiner performed all ultrasound examinations. Based on the examiner's subjective evaluation using gray scale and Doppler ultrasound findings a presumptive diagnosis (benign or malignant) was provided after real-time ultrasound was performed. Once real-time was done a 3D volume of the adnexal mass was acquired and stored by this examiner. Two examiners, unaware of the real-time ultrasound results, evaluated the 3D volumes using multiplanar display and virtual navigation and also had to provide a presumptive diagnosis (benign or malignant). These two examiners, like the first one, had information about patient's age, menopausal status and complaints. All women underwent surgery or were followed-up until cyst resolution. Histologic diagnosis was used as gold standard. Cysts that resolved spontaneously were considered as benign for analytical purposes. The Kappa index was used to assess the agreement between real time ultrasound and 3D volume analysis. Sensitivity and specificity of both methods were calculated and compared using McNemar test.Results: Forty-one masses were malignant and 58 were benign. Agreement between real-time ultrasound and 3D volume analysis was good for both off-line examiners (Kappa index: 0.82, 95% CI: 0.70–0.93 and 0.78, 95% CI: 0.65–0.90). Sensitivities for real-time ultrasound and 3D volume analyses were 100%, 93% and 90%, respectively (p>0.05). Specificities for real-time ultrasound and 3D volume analyses were 91%, 84% and 86%, respectively (p>0.05).Conclusions: Off-line 3D volume analysis may be a useful method for assessing adnexal masses, showing a good agreement with real-time ultrasound and having a similar diagnostic performance.

Amenorrhea and weight loss: not only anorexia nervosa - Corrected Proof

2011-12-15

We read with great interest the article by Michala and Antsaklis about the gynecological manifestations of anorexia nervosa (AN). This field is particularly interesting for the people involved in the clinical management of young girls, as in this age group there is certainly the highest magnitude of eating disorders. We report a case regarding the association between eating disorders and gynecological complaints to increase the spectrum of the potential underlying diseases.

Essure® hydrosalpinx occlusion prior to IVF-ET as an alternative to laparoscopic salpingectomy - Corrected Proof

Velja Mijatovic, Kim Dreyer, Mark Hans Emanuel, Roel Schats, Peter G.A. Hompes — 2011-12-15

Abstract: Objective: To investigate the success rate of proximal tubal occlusion with Essure® devices in subfertile women with unilateral or bilateral hydrosalpinx and to observe the results of subsequent treatment with IVF-ET and/or frozen embryo transfer.Study design: Prospective, single-arm, clinical study in 20 women with unilateral or bilateral hydrosalpinges (all visible on transvaginal ultrasound) due to undergo IVF-ET and/or frozen embryo transfer. In all patients, laparoscopy was considered to be contraindicated due to extensive pelvic adhesions.Result(s): In all patients the Essure® devices were placed in an ambulant setting without any complications. Proximal tubal occlusion was confirmed by hysterosalpingography in 19 out of 20 patients (95%) and in 26 of 27 treated tubes (96%). After 45 embryo transfer procedures in 19 patients, 18 pregnancies with 12 live births, 6 miscarriages and 1 immature delivery (probably related to cervical insufficiency leading to chorioamnionitis and subsequent rupture of the membranes) were observed.Conclusion(s): Essure® devices are effective in inducing proximal tubal occlusion in subfertile patients with hydrosalpinges. After artificial reproductive treatments a cumulative live birth rate per patient of 63% and a cumulative live birth rate per transfer of 27% were achieved. The latter was related to the large proportion of patients with severe endometriosis.

The impact of plasma fibrinogen levels on patients with vulvar cancer - Uncorrected Proof

2011-12-15

Abstract: Objective: To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters.Study design: In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients’ survival.Results: Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p=0.001), lymph node involvement (pN0 vs. pN1, p=0.04), and histological grade (G1 vs. G2 vs. G3, p=0.03), but not with patients’ age (≤70 years vs. >70 years, p=0.6). In a multivariate survival analysis, tumor stage (p=0.006/p=0.02) and lymph node involvement (p<0.001/p<0.001), but neither histological grade (p=0.2/p=0.9) nor plasma fibrinogen levels (p=0.6/p=0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤70 years vs. >70 years) was associated with overall survival (p=0.03) but not with disease-free survival (p=0.1).Conclusion: Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.

The use of gonadotrophin-releasing hormone (GnRH) analogue in endometroid adenocarcinoma of the ovary: a case report and discussion - Corrected Proof

2011-11-28

Dear Editor, Endometroid adenocarcinoma is a subtype of epithelial ovarian cancer which is found to be related to endometriosis. The prevalence of this tumour subtype is extremely low in women under 30 years, with a rate of 4 per 100,000 . Endometriosis contributes to subfertility and its pathogenesis remained poorly understood. This enigma is further complicated by the possibility of malignant transformation in 0.7–1% . Concerns arise when the cancer occurs in women of reproductive age where fertility is an important issue. As Wilkinson et al. found that gonadotrophin-releasing hormone receptor inhibits epithelial tumour growth and suppresses endometriosis, we report a case of early stage endometroid ovarian cancer medically managed using GnRH analogue when conventional treatment was declined.

Comparison of saline infusion sonohysterography and hysteroscopy in diagnosis of premenopausal women with abnormal uterine bleeding - Corrected Proof

2011-11-28

Abstract: Objective: The aim of this study was to compare the diagnostic effectiveness of transvaginal sonography (TVS), saline infusion sonohysterography (SIS), and diagnostic hysteroscopy (HS), with the pathologic specimen as a gold standard diagnostic method, in detecting endometrial pathology in premenopausal women with abnormal uterine bleeding.Study design: This prospective cohort study was conducted at Zeynep Kamil Education and Training Hospital, Istanbul, Turkey, and included 89 premenopausal women. All participants were examined first by TVS, further investigated with SIS and HS, and finally dilatation and curettage was performed when needed. The results obtained from these three methods were compared with the pathologic diagnoses. The positive and negative likelihood ratios (LR+ and LR−) of TVS, SIS and HS were calculated by comparison with the final pathological diagnosis. In addition, area under the curve (AUC) values were also calculated.Results: Polypoid lesion was the most common abnormal pathology. LR+ and LR− of TVS, SIS, and HS were 3.13 and 0.15, 9.83 and 0.07, 13.7 and 0.02 respectively in detection of any abnormal pathology, and the AUCs of TVS, SIS, and HS were 0.804, 0.920, and 0.954 respectively. When the three procedures were compared with each other separately, HS had the best diagnostic accuracy, and the diagnostic accuracy of HS and SIS was superior to TVS (p1=0.000, p2=0.000). For the detection of polypoid lesions, HS was the most accurate diagnostic procedure (AUC=0.947), followed by SIS (AUC=0.894) and TVS (AUC=0.778).Conclusion: HS provides the most accurate diagnosis and allows treatment in the same session in premenopausal women with abnormal uterine bleeding.