David Shveiky

Intensive management and early delivery reduce antenatal mortality in monoamniotic twin pregnancies

Background.u2002 Intensive management and elective delivery between 32 and 35 weeks of monoamniotic twin pregnancies were suggested as improving perinatal outcome. We sought to evaluate this management as viewed by the outcome of monoamniotic twin pregnancies in our population.

Prognostic parameters for successful external cephalic version

Objective. To improve patient consultation before external cephalic version (ECV) attempt at term by defining prognostic parameters for the success of the procedure. Methods. This was a prospective observational study set in a university teaching hospital. We prospectively collected demographic and obstetric data from 603 ECV attempts at our center for the period between January 1997 and June 2005. Analysis was performed by stepwise logistic regression of the demographic and obstetric parameters. The main outcome measure was success of ECV attempt. Results. Success rates were 72.3% and 46.1% for multiparas and nulliparas, respectively. Prognostic parameters associated with successful ECV were amniotic fluid index > 7 cm, multiparity, non-frank breech, non-anterior placental location, and body mass index < 25. Conclusion. Prognostic parameters, particularly amniotic fluid index and multiparity, can help physicians in counseling parturients before deciding on ECV.

Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3α and cyclin D2 in the pathophysiology

OBJECTIVEnTo identify changes in the expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt protein kinases controlling survival and/or apoptosis of in vitro cell cultures of uterine leiomyomas.nnnDESIGNnEstablishment of paired cell cultures of leiomyoma and myometrial specimens.nnnSETTINGnHadassah gynecology research laboratory.nnnPATIENT(S)nEleven white premenopausal women, 35 to 50 years of age, undergoing hysterectomy because of symptomatic uterine leiomyomas.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nImmunochemical analysis of expression and phosphorylation of relevant PI3K/Akt and BCL2 proteins.nnnRESULT(S)nAnalysis of total phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and of nonphosphorylated and phosphorylated (p) PDK1, Akt, glycogen synthase kinase 3 (GSK3), FKHR, tuberin (TSC2) and hamartin (TSC1) complex, and cyclin D2 proteins indicated that [1] the level of pGSK3alpha and cyclin D2 proteins was elevated significantly in the leiomyoma compared with the normal myometrium, [2] there was a significant interaction between PTEN- PDK1 and between pAkt-pGSK3beta in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3alpha in the paired leiomyoma and myometrial cultures.nnnCONCLUSION(S)nOur study suggests that the downstream signaling components of the PI3K/Akt pathway, GSK3 (a regulator of apoptosis), and cyclin D2 (a promoter of G1/S progression), as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3beta, are involved in the survival and proliferation of leiomyomas.

Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface

ABSTRACT Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. IMPORTANCE In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission.

Treatment of recurrent IVF failure and human leukocyte antigen similarity by intravenous immunoglobulin

This study sought to assess the efficacy of intravenous immunoglobulin (IVIg) in improving pregnancy rates and outcome, in a select group of patients with repeated IVF failure and human leukocyte antigen (HLA) similarity. Couples suffering from recurrent IVF failure, defined as at least seven attempts at embryo transfer with no successful implantations, who were found to share at least three HLA loci, and a negative cross-match test, were included in the study. The treatment consisted of two 30 g IVIg doses: one before oocyte retrieval, and a second as soon as a fetal pulse was identified on ultrasound. Ten couples comprised the study group. In total, these couples had undergone 98 IVF cycles with no successful pregnancies prior to initiation of the study. Following a total of 18 IVIg courses, seven women conceived, two women twice. Up to date, five women have delivered at least one live fetus, at 27 weeks or later. One woman is currently in the early third trimester of a twin pregnancy, and one woman had a late abortion at 19 weeks. The results suggest that couples with recurrent IVF failure and HLA similarity, may benefit from IVIg treatment.

Monoamniotic twins: an update on antenatal diagnosis and treatment

OBJECTIVEnMonoamniotic twins are very uncommon and are characterized by a high perinatal mortality rate. Cord entanglement, prematurity, congenital anomalies and twin to twin transfusion are reportedly the main causes of death, which usually occurs before 24 weeks gestation. The aim of this study was to review the newly developed methods for diagnosis and treatment and suggest a reasonable approach to the management of these rare cases.nnnMETHODnWe reviewed the English-language literature in the past 15 years through Medline search and subsequent examination of individual publications.nnnRESULTSnIn the past two decades, newer technologies such as advanced ultrasonography and color flow Doppler studies have enabled early diagnosis of this condition and its complications. Furthermore, new treatment modalities such as fetoscopy with laser coagulation of vascular anastomoses and treatment with non-steroidal anti-inflammatory drugs such as sulindac, to reduce amniotic fluid volume, may have contributed to a better outcome. Also, occlusion of one umbilical cord (fetal reduction) at an early stage has been suggested to prevent late complications.nnnCONCLUSIONnCumulative experience suggests that the majority of cases can be diagnosed reliably at an early gestational age. Treatment with medical amnioreduction, surgical amnioreduction or fetal reduction in selected cases may be offered before 24 weeks gestation. Later, intensive antepartum fetal surveillance should probably be offered until 32 weeks, at which point elective preterm delivery may be considered to prevent possible fetal death.

Hysterectomy and urinary incontinence in postmenopausal women

Introduction and hypothesisTo evaluate an association between hysterectomy and urinary incontinence (UI) in postmenopausal women.MethodsWomen (aged 50–79) with uteri (Nu2009=u200953,569) and without uteri (Nu2009=u200938,524) who enrolled in the Women’s Health Initiative (WHI) Observational Study between 1993 and 1996 were included in this secondary analysis. Baseline (BL) and 3-year demographic, health/physical forms and personal habit questionnaires were used. Statistical analyses included univariate and logistic regression methods.ResultsThe baseline UI rate was 66.5xa0%, with 27.3xa0% of participants having stress urinary incontinence (SUI), 23xa0% having urge UI (UUI), and 12.4xa0% having mixed UI (MUI). 41.8xa0% of women had undergone hysterectomy, with 88.1xa0% having had the procedure before age 54. Controlling for health/physical variables, hysterectomy was associated with UI at BL (OR 1.25, 95xa0% CI 1.19, 1.32) and over the 3-year study period (OR 1.23, 95xa0% CI 1.11, 1.36). Excluding women with UI at BL, a higher incidence of UUI and SUI episodes was found in hysterectomy at year 3. Among women who had undergone hysterectomy, those with bilateral oophorectomy (BSO) did not have increased odds of developing UI at BL or over the 3-year study period. Hormone use was not associated with a change in UI incidence (estrogen + progesterone, pu2009=u20090.17; unopposed estrogen, pu2009=u20090.41).ConclusionsRisk of UI is increased in postmenopausal women who had undergone hysterectomy compared with women with uteri.

Asymmetric large for gestational age newborns in pregnancies complicated by diabetes mellitus: is maternal obesity a culprit?

Objective: Evaluate the association between body mass index (BMI) and the delivery of an asymmetrically large for gestational age (A-LGA) newborn in women with diabetes. Methods: Retrospective analysis of 306 pregnancies complicated by Type 1 and 55 by Type 2 diabetes. Results: The prevalence of Type 1 and Type 2 diabetics delivering large for gestational age (LGA) infants was 42% and 49%, respectively. Of these 49% and 55% were A-LGA, respectively. Pre-pregnancy BMI was not associated with increased odds of delivering an A-LGA newborn in women with Type 1 or 2 diabetes. However, in Type 1 diabetics, each one-pound increase in maternal weight during pregnancy resulted in 4% increased odds of delivering an A-LGA newborn. For Type 2 diabetics, the odds of delivering an A-LGA infant was decreased by 10% for each 0.1 unit/kg increase in insulin dose. Conclusion: Although there is a known association between obesity and LGA in women with diabetes, we found that overweight and obese women with Type 1 or Type 2 diabetes do not have increased odds of delivering an A-LGA newborn. However, insulin dose in Type 2 diabetes and maternal weight gain in Type 1 diabetes were significantly associated with the odds of delivering an A-LGA neonate.

Sacrocolpopexy for Treatment of Vaginal Apical Prolapse: Evidence-Based Surgery

Pelvic organ prolapse is a common condition that negatively affects womens quality of life. Sacrocolpopexy is an abdominal procedure designed to treat apical compartment prolapse including uterine or vaginal vault prolapse and multiple-compartment prolapse. Although traditionally performed as an open abdominal procedure, minimally invasive sacrocolpopexy, whether laparoscopic or robotic, has been successfully adopted in the practice of many pelvic reconstructive surgeons. There are many variations to this procedure, with different levels of evidence to support each of them. Herein we review the current literature on sacrocolpopexy, with emphasis on the minimally invasive approach. Procedural steps and controversies are examined in light of the existing literature, and recommendations are made on the basis of the level of existing evidence.

Gene expression in women conceiving spontaneously over the age of 45 years

OBJECTIVEnTo examine gene expression profiles of women conceiving spontaneously after the age of 45.nnnDESIGNnExpression profiling by complementary DNA microarray analysis.nnnSETTINGnUniversity departments.nnnPATIENT(S)nEight women 45 years or older (study group) who conceived spontaneously and were 6 months after their last delivery were compared with six women aged 45 years old (control group) who had their last delivery before the age of 30.nnnINTERVENTION(S)nBlood samples were collected from each woman for RNA isolation from peripheral blood mononuclear cells (PBMC).nnnMAIN OUTCOME MEASURE(S)nExpression profiles of PBMC isolated from each woman were determined by using Affymetrix DNA microarray analysis covering about 15,000 identified genes.nnnRESULT(S)nMicroarray of global gene expression revealed 671 genes that showed statistically significant differential expression between the study and control groups: 383 genes were overexpressed and 288 were underexpressed. The most significant functional groups defining these genes were: apoptosis, ubiquitination, and energy production. As many as 60 genes also participated in ovarian physiology.nnnCONCLUSION(S)nThese observations suggest that extended fertility is associated with a unique ability to enrich cellular processes, leading to delayed ovarian senescence.