Exploring the factors affecting classification and reporting of uncertain prenatal microarray findings, using a "virtual fetus" model-a pilot study.

OBJECTIVE: Significant discrepancy exists between laboratories in classification and reporting of copy number variants (CNVs). Studies exploring factors affecting prenatal CNV management are rare. Our "virtual fetus" pilot study examines these factors. METHOD: Ten prenatally diagnosed CNVs of uncertain significance (VUS) > 1Mb, encompassing OMIM-morbid genes, inherited from healthy parents, were classified by 15 MD geneticists from laboratory, prenatal, and preimplantation genetic testing (PGT) units. Geneticists addressed factors affecting classification, obligation to report, and recommendation for invasive testing or PGT. RESULTS: CNVs were classified likely benign (10.7%), VUS (74.7%), likely pathogenic (8.7%), or pathogenic (6.0%). Classification discrepancy was higher for losses versus gains. Classifying pathogenic/likely pathogenic was more common for losses (adjusted odds ratio [aOR] 10.9, 95% CI 1.55-76.9), and geneticists specializing in gynecology (aOR 4.9, 95% CI 1.03-23.3). 84.0% of respondents would report CNVs, depending on classification and family phenotype. Invasive testing in pregnancies was recommended for 29.3% of CNVs, depending on the classification and geneticist's specialization. PGT was recommended for 32.4%, depending on classification, experience years, and family's phenotype (38.0% for patients undergoing in vitro fertilization irrespectively, 26.7% otherwise). CONCLUSION: Factors affecting CNV classification/reporting are mainly dosage, family phenotype, geneticist specialization and experience. Understanding factors from our pilot study may facilitate developing an algorithm for clinical consensus and optimal management.

Can hair steroids predict pregnancy longevity?

Maintaining pregnancy to term is important as preterm delivery is a risk factor for impaired infant development, which may have negative long-term consequences. Therefore, developing biomarkers that can predict pregnancy longevity during early gestation is essential for the prevention of preterm birth. Here we explored whether maternal hair testosterone and cortisol, representing the pre-conception and first trimester periods respectively, may be used to predict pregnancy longevity. We recruited 125 pregnant women that contributed hair samples and answered a personal information questionnaire that included pre-conception smoking. We quantified steroids using commercial enzyme-linked immunosorbent assay kits. Gestational age at delivery was obtained from medical records. We used General Linear Models to predict gestation length. The model that included first trimester cortisol, pre-conception smoking, pre-conception testosterone and the interaction between first trimester cortisol and pre-conception smoking predicted 13% of the variance in gestation length (R2 = 0.130; n = 105; p = 0.007). First trimester cortisol was the best predictor of gestational length. Women with high levels of cortisol in their first trimester had an increased probability of a full-term delivery. The effect of cortisol was especially pronounced in smokers (ß = 1.69), compared to non-smokers (ß = 0.45). Pre-conception testosterone also contributed to the model. Our study suggests that hair steroids may be used to predict pregnancy longevity, together with other contributing factors.

Is there an association between maternal anxiety propensity and pregnancy outcomes?

BACKGROUND: Several studies have shown inconsistent associations between anxiety during pregnancy and adverse pregnancy outcome. This inconsistency may be due to lack of controlling for the timing and type of maternal anxiety. We aimed to isolate a specific type of anxiety - maternal anxiety propensity, which is not directly related to pregnancy, and evaluate its association with adverse pregnancy outcome. METHODS: We conducted a prospective observational study of 512 pregnant women, followed to delivery. The trait anxiety scale of the State-Trait Anxiety Inventories was used in order to detect a propensity towards anxiety. The association between anxiety propensity (defined as trait-anxiety subscale score above 38) and adverse pregnancy outcome was evaluated. Primary outcome was a composite outcome including preterm birth prior to 37 gestational weeks, hypertensive disorders in pregnancy, small for gestational age newborn and gestational diabetes mellitus. Secondary outcomes were each one of the above mentioned gestational complications. RESULTS: There were no significant between-group differences in adverse pregnancy outcomes, including the rate of preterm birth, hypertensive disorders, small for gestational age, gestational diabetes or a composite outcome of them all. CONCLUSION: Anxiety propensity is not associated with adverse pregnancy outcome.

Diagnosis of deep pelvic masses on a gynaecology service: Trans-vaginal ultrasound-guided needle aspiration of pelvic solid and cystic lesions.

OBJECTIVES: Women with undiagnosed pelvic lesions are often referred for evaluation and treatment. Transvaginal ultrasound-guided fine needle aspiration (TVUS-FNA) biopsy can assist in making management decisions. We describe our experience with this modality. METHODS: We performed a retrospective chart review of all women who had a TVUS-FNA biopsy between January 2004 and December 2014. Charts were reviewed for clinicopathologic information. The pathologic results of the TVUS-FNA were compared with the final diagnosis. RESULTS: Fifty-nine women underwent TVUS-FNA; the median age was 66 years (range 27-85). Thirty-three lesions were evaluated by fine-needle aspiration biopsy of the solid structure and 26 by aspiration of fluid for cytology. Pathologic feasibility rate was 88% (52/59). Of those with evaluable tissue, the sensitivity of the procedure was 100% and the specificity 92%. Considering the seven inconclusive results, the procedure had sensitivity of 88% (29/33) and specificity of 88% (23/26). Overall accuracy of TVUS-FNA for this patient cohort was 85%. No patient characteristics were found to distinguish between accurate and inaccurate or inconclusive TVUS-FNA result. No complications were noted. CONCLUSIONS: TVUS-FNA offers an excellent modality for the diagnosis and management of deep pelvic lesions otherwise not amenable for histologic evaluation.

Uterine electrical activity at labor: is there a correlation between labor stages?

OBJECTIVE: To determine the association between the myometrial electrical activity in the active and second stages of labor at term using electrical uterine myography (EUM). METHODS: A prospective observational study of 47 singleton deliveries at term in a tertiary hospital. All women were assessed using noninvasive 9-channel surface electrodes of the EUM during labor. EUM index (EUMi) was calculated as the mean electrical activity during a 30 min monitoring period and expressed as microjouls (MJ). Mean EUMi of the active and second stages of labor were compared accordingly. RESULTS: Mean EUMi during the active phase was 3.53 ± 0.43 MJ, whereas mean EUMi in the second stage was 3.66 ± 0.48 MJ (p = 0.02). Correlation analysis between mean EUMi of the active and second stages of labor produced r2 = 0.68 (p < 0.01). In a regression analysis model EUMi of the active stage of labor remained strongly correlated with the duration of the second stage (r2 = 0.73, p < 0.001). No correlation was found between EUMi and the duration of the second stage. CONCLUSION: A positive correlation of myometrial electrical activity exists between active phase and second stage of labor. However, while EUMi was associated with the duration of the active phase, no correlation was found between EUMi and the duration of the second stage.

Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection.

OBJECTIVES: This study aimed to evaluate antenatal risk factors associated with symptomatic congenital cytomegalovirus (CMV) disease, following in utero vertical infection. METHODS: This study included a retrospective cohort of 155 neonates with congenital CMV infection, following primary maternal CMV infection during pregnancy, and were divided to symptomatic (n=95) and asymptomatic (n=60) newborns. RESULTS: Young maternal age (29.1±5.12 vs. 31.6±5.36 years, P=0.005), high risk occupation for viral exposure (20.0% vs. 11.7%, P=0.04), CMV IgG seroconversion at diagnosis (83.1% vs. 63.3%, P=0.005) and abnormal fetal MRI (11.6% vs. 0%, P=0.003) were found to be prognostic risk factors associated with symptomatic CMV disease of the newborn. Maternal febrile illness at diagnosis, IgG avidity, US findings and the timing of maternal infection were not associated with the occurrence of neonatal symptoms. CONCLUSIONS: Knowledge of the reported risk factors may assist in counseling parents with intra uterine CMV infection.

Association of isolated polyhydramnios at or beyond 34 weeks of gestation and pregnancy outcome.

OBJECTIVE: To evaluate pregnancy outcome among women with isolated polyhydramnios at admission for labor at or beyond 34 weeks of gestation. METHODS: Retrospective cohort study at a tertiary medical center between 2007 and 2012. Isolated polyhydramnios was defined as amniotic fluid index (AFI) greater than 25 cm at admission in the absence of gestational or pregestational diabetes mellitus or fetal structural or chromosomal anomalies. Women with isolated polyhydramnios were compared with women with a normal AFI (5-25 cm). RESULTS: Overall, 31,376 women were eligible for analysis, of whom 215 (0.7%) had isolated polyhydramnios and 31,161 normal AFI. Women with isolated polyhydramnios had higher rates of labor induction (7.9% compared with 4.8%, P=.04) and cesarean delivery (12.1% compared with 5.1%, P<.001). They also had higher rates of placental abruption (0.9% compared with 0.2%, P=.02), abnormal or intermediate fetal heart rate (FHR) tracings (7.0% compared with 3.2%, P=.002), and prolonged first stage of delivery (6.0% compared with 1.4%, P<.001). Isolated polyhydramnios was also associated with higher rates of shoulder dystocia (1.9% compared with 0.3%, P<.001) and respiratory distress syndrome (0.5% compared with 0.03%, P=.001). On a multiple logistic regression model, isolated polyhydramnios was an independent risk factor for labor induction (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.01-2.8), cesarean delivery (adjusted OR 2.6, 95% CI 1.7-4.0), prolonged first stage of delivery (adjusted OR 3.6, 95% CI 1.97-6.7), abnormal or intermediate FHR tracings (adjusted OR 2.6, 95% CI 1.6-4.5), placental abruption (adjusted OR 8.4, 95% CI 2.00-35.4), shoulder dystocia (adjusted OR 3.4, 95% CI 1.2-9.7), and respiratory distress syndrome (adjusted OR 38.9, 95% CI 4.6-332.6). Mild isolated polyhydramnios (AFI 25.1-30.0) was independently associated with cesarean delivery, prolonged first stage of delivery, placental abruption, abnormal or intermediate FHR tracings, and shoulder dystocia. CONCLUSION: Isolated polyhydramnios at admission for labor at or beyond 34 weeks of gestation is associated with adverse obstetric and neonatal outcomes.

Metabolic disorder of pregnancy (understanding pathophysiology of diabetes and preeclampsia).

The role of insulin resistance in human disease is implicated in the pathogenesis of some of the chief western chronic diseases: ischemic heart disease, type 2 diabetes mellitus, and essential hypertension. The occurrence of these diseases, alongside obesity, is termed the metabolic syndrome. Pregnancy is normally attended by progressive insulin resistance that begins near midpregnancy and progresses through the third trimester to levels that approximate the insulin resistance seen in individuals with type 2 diabetes. Insulin resistance and hyperinsulinemia may be the basic common ground for the metabolic syndrome of pregnancy - elevated blood pressure and diabetes mellitus. Moreover, the metabolic syndrome is also associated with endothelial dysfunction, oxidative stress, and attenuated inflammatory responses. In this review, we discuss the development of insulin resistance during pregnancy, hormones and newly discovered factors associated with insulin resistance and secretion, lipid metabolism, and the pathogenesis of hypertension during pregnancy.

Predictors of successful external cephalic version and assessment of success for vaginal delivery.

OBJECTIVE: To identify predictors of successful external cephalic version (ECV) and to compare delivery outcome between women who had a successful ECV and women with spontaneous vertex presentation. METHODS: A retrospective cohort study of all women who underwent ECV in a single tertiary medical center between 2007 and 2011. Delivery outcome was compared between women who underwent a trial of vaginal delivery following successful ECV with that of a control group in a 2:1 ratio. Multivariate analysis was used to identify predictors of successful ECV. RESULTS: Overall 287 were eligible for the study group. Of these 130 (45.3%) had a successful ECV. Polyhydramnios was the strongest factor associated with successful ECV (OR=3.1, 95%-CI 1.4-7.2), followed by transverse lie (versus breech presentation, OR=2.6, 95%-CI 1.2-6.7) and a posterior placenta (OR=1.7, 95%-CI 1.1-3.9), while nulliparity was associated with a lower likelihood of successful ECV (OR=0.4, 95%-CI 0.2-0.6). Women who had a successful ECV and underwent a trial of labor were more likely to deliver by operative vaginal delivery (OVD) (OR=1.8, 95%-CI 1.2-3.6), mainly due to a higher rate of prolonged 2nd, but were not at an increased risk for CS (OR=0.9, 95%-CI 0.4-2.4). CONCLUSIONS: Counselling to women prior to ECV should address the likelihood of success based on the predicting factors described above, as well as the increased risk for OVD in the case of successful ECV.

Does artificial rupturing of membranes in the active phase of labor enhance myometrial electrical activity?

OBJECTIVE: To determine whether artificial rupture of membranes (AROM) during active phase of labor augments uterine contractility using Electrical Uterine Myography (EUM). STUDY DESIGN: A prospective study of 31 women with term singleton pregnancy during active phase of labor. Using a non-invasive EUM technique, electrical uterine activity was recorded in the 30 min preceding AROM and in the immediate 30 min thereafter. Augmentation was defined as >5% increase in EUM index between the basal and post-AROM states, representing the mean EUM increase of the entire cohort. Low basal uterine contraction was defined as EUM index of less than the entire cohort median result prior AROM (3.5 micro-Watt-Second (mWS)). RESULTS: Mean dilatation in which AROM was preformed was 5.5 ± 1.8 cm. There was a significant increase in mean EUM measurement in the post-AROM compared to the basal state (3.59 ± 0.39 versus 3.42 ± 0.47 mWS, p < 0.001). In multivariate analysis, low BMI and low basal uterine contractions were the only significant predictors for augmentation following AROM (OR 0.69, 95% C.I 0.45-0.97, p = 0.009 and OR 16.03, 95% CI 1.90-134.69, p = 0.003, respectively). CONCLUSION: Myometrial electrical activity was significantly enhanced following AROM. Augmentation was mostly pronounced in patients with lower BMI and initial lower basal uterine contraction.

Factors affecting uterine electrical activity during the active phase of labor prior to rupture of membranes.

OBJECTIVE: Limited data exist regarding uterine contraction intensity prior to membrane rupture. Using a novel technique of electrical uterine myography (EUM) we aimed to determine which factors affect myometrial activity during active phase of labor. METHODS: EUM was prospectively measured in 37 women with singleton pregnancy at term during the active phase of labor until membranes' rupture. EUM was measured using non-invasive nine channels recorder with an EMG amplifier and three-dimensional position sensor. Uterine electrical activity was quantified with the EUM-index, defined as the mean electrical activity of the uterine muscle over a period of 10 min and measured in units of micro-Joule (microwatt per second [mW/s]). RESULTS: The mean EUM-index at the first 10 min of the measurement was 3.3 ± 0.6 mW/s. In a stepwise linear regression model accounting potential confounders EUM was significantly affected by cervical dilatation (p = 0.005), maternal age (p = 0.04) and previous cesarean delivery status (p = 0.02). In a repeated measurement assessment of non-parametric Fridman's test for all subjects who had at least 10 continuouss EUM measurements, there was a significant increase in electrical uterine activity as labor progressed (p = 0.01). CONCLUSION: Electrical uterine activity during the active phase of labor prior to rupture of membranes is affected by maternal age, previous cesarean delivery status and cervical dilatation. Moreover, electrical uterine activity is enhanced throughout labor.

[On gods, snakes and staffs--the emblem of the medical profession].

The commonly accepted emblems of the Medical Profession are the staff of the Greek god of medicine--Asklepios (or Asclepius], on which one serpent is entwined. Later, around the 16th century C.E., the wand of the herald of the Greek Gods, e.g., Hermes, on which two snakes are entwined and facing each other, became popular as the emblem of the medical profession. We elaborate on the history of the evolution of these emblems as symbols of medicine, including earlier influences from the times of the ancient Egyptians and Babylonians, which were followed by Judeo-Christian traditions and concepts. The relevance of the use of the wand of Hermes as an emblem of our profession is further discussed.

Uterine electric activity during the third stage of labor; a look into the physiology of a deserted stage.

OBJECTIVE: To evaluate uterine activity during the third stage of labor and compare it to that observed in the second stage of labor. STUDY DESIGN: Uterine electric activity was prospectively measured using electrical uterine myography (EUM) in 44 women with singleton pregnancy at term during the final 30 min of the second stage and throughout the third stage of labor. Results are reported using a scoring index of 1-5 mWS (micro-Watt-Second). Patients were stratified into two groups based on the duration of the third stage (<15 min and >=15 min) RESULTS: The mean durations of the second and third stages were 51.9 ± 63.5 and 15.4 ± 7.5 minutes, respectively. During the third stage, uterine activity (contractions peaks) was similar to that observed during the second stage of labor (3.43 ± 0.64 mWS versus 3.42 ± 0.57 mWS, p = 0.8). No correlation was found between the duration of the third stage and EUM measurements during the third (p = 0.9) or the second (p = 0.2) stages of labor. No association was found between EUM measurements during the third stage and parity, maternal age, fetal weight, duration of labor, gestational age, gravity or BMI. The rate of oxytocin use during the second stage and EUM measurements during the second or third stage did not differ among women with short versus long duration of the third stage. CONCLUSION: Uterine activity during the third stage is comparable and as intense as that occurring during the second stage. Third stage length cannot be predicted by contraction intensity during the second or third stage of labor.

Work satisfaction, quality of life, and leisure time of neonatology fellows and senior neonatologists in Israel.

OBJECTIVES: To examine work satisfaction, quality of life, and leisure time of neonatology fellows and senior neonatologists in Israel. METHODS: A validated questionnaire was delivered during the second half of 2008 to all the neonatology fellows and senior neonatologists in Israel. Descriptive analysis, parametric Student's t-test, and aparametric Mann Whitney and χ2 tests were conducted. RESULTS: Of 114 practicing neonatologists in that period in Israel (including both seniors and fellows), 112 (98.25%) participated in the study. The majority of neonatologists were male (53.2%), married (91.7%), 40-60 years old (69.7%), and studied in Israeli medical schools (62.0%). Most did their pediatric residencies and fellowships in Israel (97.2% and 75.7%, respectively). The average number of night/on-call shifts of fellows and senior neonatologists was 8.8 per month (SD ± 3.425) and the number of active on-call shifts was 4.04 (SD ± 3.194). The satisfaction level of neonatologists in Israeli medical centers with patient care, self-reward, work relations, and quality of life was high, but their satisfaction level with workload, income and prestige, and leisure time was low. The general index of work satisfaction and the general index of indices were both high in relation to the mid-range values. The majority of neonatologists stated that they would choose to practice medicine again. Most of them would encourage medical students to choose the same specialty they had chosen. Only a few neonatologists were contemplating changing their choice of specialty. Most neonatologists want to continue practicing medicine; however, a significant number will not recommend that their children do so. CONCLUSIONS: The satisfaction level of neonatologists in Israel is high, mainly due to satisfaction with their work. High satisfaction levels promise high quality patient care, as well as high satisfaction levels of patients and their families. However, satisfaction with leisure time was low and it will require greater attention and focused steps to correct this.

Outcomes of mid-trimester emergency cerclage in twin pregnancies.

INTRODUCTION: Placement of emergency cerclage at mid-trimester is controversial. At present, clinical trials comparing outcomes of mid-trimester cerclage to bed rest in twin pregnancies are lacking. Our aim was to examine the efficacy, safety and outcomes of mid-trimester cerclage in patients carrying twin gestations. MATERIAL AND METHODS: We retrospectively studied the outcomes of 14 patients carrying twin gestations with significant cervical dynamics who underwent cerclage. Outcomes of patients with cervical effacement only and patients with bulging membranes through the external os were examined. The interval between cerclage and delivery and the complication rates were calculated. RESULTS: The average time interval between cerclage placement and delivery was 71.1 days overall. Patients with cervical shortening or effacement only (n = 10) gave birth an average of 80.2 days after the procedure, while 4 patients with bulging membranes gave birth an average of 48.5 days after cerclage placement. The overall procedure failure rate, defined as delivery before 28 completed weeks, was 14.2%. DISCUSSION: Patients carrying twin gestations with advanced cervical changes might benefit from therapeutic cerclage. Further studies are required to demonstrate whether there is a difference compared to bed rest alone.

Risk factors for relaparotomy after cesarean delivery.

OBJECTIVE: To identify risk factors for relaparotomy after cesarean delivery. METHODS: Cases of exploratory laparotomy at Lis Maternity Hospital, Tel Aviv, Israel, following cesarean delivery between 2000 and 2010 were reviewed retrospectively. Each case in the study group was matched randomly with 5 control cases in which the patient underwent cesarean delivery only. Demographic and clinical data before and during the primary procedure were compared. RESULTS: Twenty-eight (0.2%) of 17482 cesarean deliveries were followed by exploratory relaparotomy. Significant differences between the study and the control (n=140) groups were found in: placental abruption as an indication for cesarean (17.8% vs 0.6%; P=0.004); duration of primary operation (45.3 ± 21.1 vs 29.9 ± 11.8 minutes; P=0.007; 95% CI, 5.1-19.2); and experience of chief surgeon (10.1 ± 1.6 vs 5.8 ± 0.4 years; P=0.02; 95% CI, 0.0-5.0). Findings during relaparotomy were: abdominal wall bleeding/hematoma (n=4 [14.2%]); uterine scar bleeding (n=4 [14.2%]); retroperitoneal bleeding (n=1 [3.5%]); adhesions causing bowel obstruction (n=1 [3.5%]); and uterine scar gangrene (n=1 [3.5%]). There were no findings for 17 (60.7%) patients. CONCLUSION: The incidence of relaparotomy following cesarean was 0.2% (1 per 624 cesarean deliveries). Significant risk factors were placental abruption and longer operative time.

[Obstetrics and gynecology workforce planning: the Israeli experience 1995-2025].

BACKGROUND: Currently, there is no current obstetricians and gynecologists' workforce (OBGW) planning in Israel. Forecasting the OBGW is a challenge in order to achieve optimal obstetrics and gynecology care in the next decades. OBJECTIVE: To examine the current Israeli OBGW and to describe, using an equation, the future supply of OBGW, until 2025. METHODS: A descriptive study of past (1995-2006) and future (through 2025) OBGW trends in Israel. An equation was developed to project physician supply until 2025. RESULTS: No "optimal ratio" exists regarding OBGW to female population ratio. In addition, information regarding OBGW planning is scarce. In Israel, the ratio of OBGW aged < 65 years per 1000 females aged > or = 15 years, was 0.35 in 2006, 23% more than the higher projected ratio from USA for 2005. In 2020, for comparison, the ratio in Israel will be 18% higher than the US ratio. The ratio calculated by the equation presents a plateau of the supply of Ob-Gyn specialists in Israel until 2025. A continued significant growth in the number of Ob-Gyn female specialists, compared with males, is noted. The interpretation of this data requires further evaluation. CONCLUSIONS: In order to preserve the quality of care, there is a need for continuous monitoring and structured planning of health care human resources and OBGW in particular. Research and data in this field are scarce and, therefore, there is a need to conduct many additional research studies. Furthermore, additional data collection is needed to evaluate quality of care and its availability according to the relation between manpower needs and expected demands in Israel's health system.