Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Objective Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. Methods NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. Results In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5th centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Conclusions Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies. Copyright. 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Correlates of human immunodeficiency virus cervicovaginal shedding among postmenopausal and fertile-aged women

Objective: The aims of this study were to compare the intensity of human immunodeficiency virus (HIV)-RNA genital shedding among postmenopausal (PM) and fertile-aged (F) women and to investigate the association between viral shedding and gynecological features, HIV plasma viral loads, and other markers of HIV disease progression. Methods: We interviewed 146 HIV-infected women (73 PM/73 F) in search of gynecological complaints and signs and symptoms of HIV disease and obtained additional information concerning HIV infection by medical chart review. Cervicovaginal lavages (CVLs) were collected for assessment of HIV shedding. Laboratory analyses included CD4(+) cell counts, HIV-RNA quantitation in plasma and CVL, and screening for concurrent genital infections. Results: HIV-RNA genital shedding was detected in 16.4% of PM and 21.9% of F women (P = 0.400), and the intensity of HIV shedding did not differ between both groups (means-PM: 1.4log/mL; F: 1.4log/mL; P = 0.587). Three women (2 PM/1 F) exhibited viral shedding in the absence of detectable viremia. HIV plasma viral loads correlated with HIV shedding in both groups. In multivariable analysis, HIV plasma viral loads were independently associated with HIV shedding in both groups. Moreover, the intensity of shedding was independently associated with vaginal pH, tumor necrosis factor a concentrations in CVL, and HIV plasma viral loads. Conclusions: Despite significant changes that occur in the vaginal mucosa of PM women, HIV cervicovaginal shedding was not significantly influenced by this state in our cohort. In contrast, increased vaginal pH and genital inflammation, evidenced by increased tumor necrosis factor alpha concentrations in CVL and HIV plasma viral loads, were independently associated with the intensity of HIV shedding in PM and F women.

Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat

OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test. RESULTS: CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH. CONCLUSION: Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.

Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome

Objective To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria. Methods This was a case- control study evaluating 90 obese women ( body mass index ( BMI) = 30.0 kg/m2 and < 40 kg/m2) aged between 18 and 40 years without any other health condition that could interfere with COC eligibility criteria, of whom 45 had PCOS and 45 were age- matched controls. BMI, waist and hip circumference, arterial blood pressure, fasting insulin and glucose, quantitative insulin sensitivity check index ( QUICKI), highdensity lipoprotein cholesterol, low- density lipoprotein cholesterol, total cholesterol, triglycerides, testosterone, sex hormone- binding globulin, free androgen index ( FAI), carotid stiffness index, intima media thickness, flowmediated dilatation ( FMD) of the brachial artery and non- alcoholic fatty liver disease ( NAFLD) were assessed. Results In women with PCOS, we observed a higher frequency of NAFLD ( 73.3 vs. 46.7%, P < 0.01) and higher FAI ( 10.4 vs. 6.8%, P < 0.01). We also observed a trend towards increased insulin levels ( 10.06 +/- 6.66 vs. 7.45 +/- 5.88 mu IU/mL, P = 0.05), decreased QUICKI ( 0.36 +/- 0.06 vs. 0.39 +/- 0.07, P = 0.05) and decreased FMD ( 7.00 +/- 3.87 vs. 8.41 +/- 3.79%, P = 0.08). No other significant difference was observed. Conclusions NAFLD is frequent in obese women without any other health condition that could interfere with COC eligibility criteria, especially in those with PCOS. This should be considered when choosing the best contraceptive option. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia

Objective Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. Methods Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. Results Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 +/- 2.4 weeks in the FETO group and at 37.4 +/- 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the receivedtreatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). Conclusion FETO improves neonatal survival in cases with isolated severe CDH. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

High-frequency TENS in post-episiotomy pain relief in primiparous puerpere: A randomized, controlled trial

Aim: We evaluated the effectiveness of high-frequency transcutaneous electrical nerve stimulation (TENS) as a pain relief resource for primiparous puerpere who had experienced natural childbirth with an episiotomy. Methods: A controlled, randomized clinical study was conducted in a Brazilian maternity ward. Forty puerpere were randomly divided into two groups: TENS high frequency and a no treatment control group. Post-episiotomy pain was assessed in the resting and sitting positions and during ambulation. An 11-point numeric rating scale was performed in three separate evaluations (at the beginning of the study, after 60 min and after 120 min). The McGill pain questionnaire was employed at the beginning and 60 min later. TENS with 100 Hz frequency and 75 mu s pulse for 60 min was employed without causing any pain. Four electrodes ware placed in parallel near the episiotomy site, in the area of the pudendal and genitofemoral nerves. Results: An 11-point numeric rating scale and McGill pain questionnaire showed a significant statistical difference in pain reduction in the TENS group, while the control group showed no alteration in the level of discomfort. Hence, high-frequency TENS treatment significantly reduced pain intensity immediately after its use and 60 min later. Conclusion: TENS is a safe and viable non-pharmacological analgesic resource to be employed for pain relief post-episiotomy. The routine use of TENS post-episiotomy is recommended.

Construction and validation of an instrument that breaks the silence: the impact of domestic and/or sexual violence on women's health, as shown during climacterium

Objective: The aim of this study was to construct and to validate a measure of the consequences of domestic violence on women's health during climacterium. Methods: A questionnaire was administered at the Outpatient Climacterium Clinic to 124 women aged 40 to 65 years who were the victims of domestic and/or sexual violence (experimental group). They were divided into three groups: (1) those who were victims of violence exclusively during childhood/adolescence, (2) those who were victims of violence exclusively during adulthood, and (3) those who were victims of violence throughout their lives. The instrument included 34 items evaluating the beginning, frequency, and type of violence; the search for health assistance and reporting of the violence; the violence and the number of comorbidities; and violence and the Kupperman Menopausal Index. We also included a control group composed of perimenopausal and postmenopausal women who did not experience any violence (n = 120). Results: The instrument presented a Cronbach alpha = 0.82, good reliability among the examiners (+0.80), and a good possibility of reproducibility. The mean age of menopause was 45.4 years, and the mean age in the control group was 48.1 years. Group 1 showed a mean of 5.1 comorbidities, Group 2 had 4.6, and Group 3 had 4.4. Sexual violence (43.5%) and other types of violence both presented average comorbidities (4.60) but represented a significant impairment in the victim's sexual life. There were significant associations in group 3 and a high Kupperman Menopausal Index score. In the experimental group, 80.6% did not seek health services for the violence they experienced. Conclusions: The questionnaire presented good internal consistency and a validated construction. It can be easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual violence on women's health during climacterium.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters

Objectives To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). Methods Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/eMPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). Results Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/eLHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/eContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). Conclusions Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

The use of parthenotegenetic and IVF bovine blastocysts as a model for the creation of human embryonic stem cells under defined conditions

Clinical application of human embryonic stem cells will be possible, when cell lines are created under xeno-free and defined conditions. We aimed to establish methodologies for parthenogenetic activation, culture to blastocyst and mechanical isolation of the inner cell mass (ICM) using bovine oocytes, as a model for derivation and proliferation of human embryonic stem cells under defined xeno-free culture conditions. Cumulus-oocyte-complexes were in vitro matured and activated using Ca(2+)Ionophore and 6-DMAP or in vitro fertilized (IVF). Parthenotes and biparental embryos were cultured to blastocysts, when their ICM was mechanically isolated and placed onto a substrate of fibronectin in StemProA (R) medium. After attachment, primary colonies were left to proliferate and stained for pluripotency markers, alkaline phosphatase and Oct-4. Parthenogenesis and fertilization presented significantly different success rates (91 and 79 %, respectively) and blastocyst formation (40 and 43 %, respectively). ICMs from parthenogenetic and IVF embryos formed primary and expanded colonies at similar rates (39 % and 33 %, respectively). Six out of eight parthenogenetic colonies tested positive for alkaline phosphatase. Three colonies were analyzed for Oct-4 and they all tested positive for this pluripotency marker. Our data show that Ca2+ Ionophore, and 6-DMAP are efficient in creating large numbers of blastocysts to be employed as a model for human oocyte activation and embryo development. After mechanical isolation, parthenogetic derived ICMs showed a good rate of derivation in fibronectin and Stem-Pro forming primary and expanded colonies of putative embryonic stem cells. This methodology may be a good strategy for parthenogenetic activation of discarded human oocytes and derivation in defined conditions for future therapeutic interventions.

Why Are Women With Cervical Cancer Not Being Diagnosed in Preinvasive Phase? An Analysis of Risk Factors Using a Hierarchical Model

Objective: To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods: This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low-or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals' care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results: The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3-48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3-4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3-13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5-35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1-0.8) for delayed diagnosis. Conclusions: Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data

OBJECTIVE: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (<= 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN: Individual patient data metaanalysis of randomized controlled trials. RESULTS: Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION: Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Health education intervention in early and late postmenopausal Brazilian women

Aim To identify aspects of health in postmenopausal Brazilian women using a health-related educational program provided by a multidisciplinary team as part of the primary care approach for early and late postmenopausal symptoms. Design A prospective cohort was formed with 69 postmenopausal women; they were divided into groups corresponding to early (n = 32) and late postmenopause (n = 37) through gynecological and clinical evaluations. We administered the Kuppermann-Blatt Menopausal Index and the Women's Health Questionnaire before and after health education instructions. Results The average age for the onset of menopause was 47.9 years (n = 69). Fifty women (72.5%) in this study had completed their primary education, 78.3% (n = 54) performed manual labor, and 60.9% (n = 42) showed concomitant chronic illnesses. After attending a series of health-related presentations, the mean weight of the women was reduced by 3.54% in early postmenopausal women (p < 0.001) and by 2.06% in the late postmenopausal group (p < 0.001). The mean abdominal circumference was reduced by 1.75% (p < 0.001) in the early postmenopausal group. In addition, the total score in the Kuppermann-Blatt Menopausal Index decreased by 34.38% in the early and by 33.33% in the late postmenopausal groups. According to the Women's Health Questionnaire, there was a decrease in the domain Depressive mood by 0.839 to 0.700 (p < 0.001) in the early and by 0.814 to 0.648 (p < 0.001) in the late postmenopausal groups. Conclusion Regardless of improving menopausal symptoms and anthropometric parameters, the effects of the multidisciplinary team activities in early postmenopausal women may be similar to those in late postmenopausal women.

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

To detect expression of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in oocytes, and their receptor type 2 receptor for BMPs (BMPR2) in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if BMPR2, BMP15, and GDF9 expression correlate with hyperandrogenism in FF of PCOS patients. Prospective case-control study. Eighteen MII-oocytes and their respective cumulus cells were obtained from 18 patients with PCOS, and 48 MII-oocytes and cumulus cells (CCs) from 35 controls, both subjected to controlled ovarian hyperstimulation (COH), and follicular fluid (FF) was collected from small (10-14 mm) and large (> 18 mm) follicles. RNeasy Micro Kit (Qiagen(A (R))) was used for RNA extraction and gene expression was quantified in each oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were used for hormone assays. BMP15 and GDF9 expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between BMPR2 transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group. We inferred that BMP15 and GDF9 transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.

Intratumoral Lymphatic Vessel Density in Vulvar Squamous Cell Carcinomas: A Possible Association With Favorable Prognosis

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

Advice on the Management of Ambiguous Genitalia to a Young Endocrinologist from Experienced Clinicians

The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. Most disorders of sexual differentiation (DSD) associated with ambiguous genitalia are the result either of inappropriate virilization of girls or incomplete virilization of boys. It is important to establish a diagnosis as soon as possible, for psychological, social, and medical reasons, particularly for recognizing accompanying life-threatening disorders such as the salt-losing form of congenital adrenal hyperplasia. In most instances, there is sufficient follow-up data so that making the diagnosis also establishes the appropriate gender assignment (infants with congenital adrenal hyperplasia, those with androgen resistance syndromes), but some causes of DSD such as steroid 5 alpha-reductase 2 deficiency and 17 beta-hydroxysteroid dehydrogenase deficiency are associated with frequent change in social sex later in life. In these instances, guidelines for sex assignment are less well established.