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Background Cesarean delivery (CD) in primiparas with a term singleton vertex fetus (PTSV) is a sentinel event for the future mode of delivery and determinant of repeat CD risk. We aimed to evaluate the risk factors for primary CD in a population with a decade of sustained low rate of intrapartum CD. Methods This was a retrospective single-center cohort study between 2005 and 2014. The primary outcome of the study was the mode of delivery. PTSV who attempted vaginal delivery were identified and categorized according to the mode of delivery: vaginal delivery vs. CD. Risk factors for intrapartum CD adjusted odds ratio (aOR) [95% confidence interval (CI)] in multivariate analysis were reported. Results During the study, 121,483 deliveries were registered; 26,301 (21.6%) PTSV were admitted in labor, of which 1944 (7.4%) had an intrapartum CD. Significantly in multivariate analysis, this group had a unique risk profile as compared to those who delivered vaginally; non modifiable risks included advanced maternal age: 3.06 (2.16–4.33), P Conclusion In a population of PTSV with a sustained low risk for intrapartum cesarean maintained by a strict labor management, induction of labor remains a significant and sole potentially modifiable risk factor for CD.

Background/aims Antenatal depression may have adverse effects on pregnancy outcomes such as preterm birth (PTB) and small-for-gestational-age neonates. Serotonin as a neurotransmitter is intimately related to stress and depression. The purpose of this study was to assess variants of the serotonin receptor (5-HT1A) gene and serotonin transporter promoter (5-HTTLPR) gene as potentially directly involved in adverse pregnancy outcomes (APOs), especially PTB. Methods A pilot case-control study over two years identifying 78 women delivered at Results Women with the s/s serotonin transporter 5-HTTLPR genotype experienced significantly more EPLs but there was no significant association between serotonin polymorphisms and preterm birth. Conclusion Two serotonin gene polymorphisms, known to be associated with depression, are hereby shown to be associated with APO. EPL, but not preterm birth, is significantly linked to an s/s serotonin transporter 5-HTTLPR genotype.

Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB. Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24–36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn. Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183–3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p

To describe prostanoid DP receptor (PTGDR) variants in women with preterm births who admitted to coital activity (CA) within 24 h of labor.To achieve80% statistical power, a pilot case-control study compared 24 premature births from mothers with CA (Group 1), 30 mothers of premature infants who did not have CA (Group 2 non-coital activity) and 95 non-coital activity mothers with term births (Group 3 controls). Four functional PTDGR single nucleotide polymorphisms (SNPs) were evaluated: T-549C, C-441/T, T-197C and G+1044A. PHASE 2.0.2 and SAS 9.2 were used for analysis.All SNPs were in Hardy-Weinberg equilibrium in controls. The C-441/T genotype frequency was significantly increased among Group 1 women relative to Group 2 and 3 women (odds ratio (OR): 30.1, 95% confidence interval (CI) 6.9-191 and 25.7 95%CI 25.7-not computible, respectively). Of the possible haplotypes among the groups, the TCTG haplotype (T-549C, C-441/T, T-197C and G+1044A) was significantly more frequent in Group 1 women compared with the control groups (OR 53.4, 95%CI 10.3-554.8).A differential genomic pattern of PTGDR polymorphisms was identified in a sub-set of mothers which was associated with an increased risk of post-coital preterm birth.

To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD).A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders.Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522).Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.

Background Recurrent pregnancy loss (RPL) has been associated with impaired maternal–fetal communication. Protease-activated-receptor 1 (PAR1) is critical for trophoblast invasion and establishment unrelated to its role in vascular biology. Objectives To analyze whether polymorphisms of PAR1 [-1426C/T], [-506I/D], and/or IVS[-14A/T] are associated with unexplained RPL. Patients/methods A case-control pilot study conducted in 39 healthy women with history of unexplained RPL and 98 women with a full-term, uncomplicated deliveries and no history of RPL. Results Women with RPL were significantly more likely to be heterozygous for [-1426C/T] (12.8% versus 3.2%; p = 0.049); the heterozygous state for IVS[-14A/T] was also more common (15.4% versus 4.4%; p = 0.064). There was no difference between groups for [-506I/D] genotypes. The functional consequence for [-1426C/T] and IVS[-14A/T] polymorphisms is underscored by the markedly low PAR1 mRNA levels in those women. Bioinformatics indicate generation of a new consensus motif for repressor Kruppel-like factor 3 (KLF3) in [-1426T]. Moreover, chromatin immunoprecipitation (ChIP) analysis confirmed a physical association between KLF3 protein and the hPar1 DNA obtained from women with the [-1426C/T] polymorphism. Conclusions We hypothesize that the significantly low PAR1 levels impact placenta establishment and consequently pregnancy outcome, thereby profiling a novel risk factor for unexplained RPL.

Objective The active form of vitamin D (1,25[OH] 2 D 3 ) has been established to have potent anti-proliferative, immuno-modulatory, and anti-microbial action in addition to its effects on bone. The nuclear vitamin D receptor (VDR) is expressed in the placenta-decidua, regulating genes associated with implantation and implantation immuno-tolerance. If VDR polymorphisms regulate VDR functionality at the placenta-decidua interface, VDR genotypes may be involved in idiopathic preterm birth (PTB). Study design Maternal and fetal (umbilical cord) blood samples from 33 Jewish and Arab mothers with PTB of a singleton neonate were compared to 98 samples from Jewish and Arab maternal and fetal blood samples from full-term, uncomplicated singleton births. Maternal age and ethnicity were comparable between groups. PCR amplification/digestion identified the VDR SNPs: FokI , ApaI , TaqI , and BsmI . Results Allele frequency for the FokI VDR in maternal blood samples from preterm births (but not umbilical cord samples) was significantly different ( p = 0.01) from that in maternal and umbilical cord blood samples from full-term singleton births, with an odds ratio for FokI carriers of 3.317 (95% CI, 1.143, 9.627) for preterm birth. The FokI VDR variant may therefore be a maternal risk trait for PTB among these women. Conclusion This study may support a future platform for the study of vitamin D during pregnancy and treatment of selective target populations with vitamin D and/or VDR “tissue-specific therapeutic intervention” for prevention of PTB.

Obstetrical hemorrhage is the second leading cause of direct maternal mortality (18% of maternal deaths) in developed countries and is the leading cause of severe maternal morbidity. The rising rate of obstetrical hemorrhage attributed to the repeated cesarean sections and invasive placental disorders, requiring blood transfusion has emphasized the need for alternatives to allogeneic blood donation.The Shaare Zedek Medical Center is a teaching hospital with the largest obstetric service in the region-13,500 live births per year. The medical records of all parturients requiring use of intraoperative cell salvage system (IOCS) (2007-2011) were reviewed to evaluate our experience with this unique system and possible complications in the obstetrical milieu of a large obstetric unit.Using our combined medical records, we found that IOCS is a rapid method of blood replacement that allows blood bank service recruitment and presents no adverse reaction to the parturient. However, this sophisticated system is appropriate for tertiary surgical centers and its routine use should be assessed by national medical boards.

Protease activated receptor 1 (PAR1), the thrombin receptor, is implicated in hemostasis, tissue remodeling, and is critical in early placentation. PAR1 polymorphisms that influence coagulation and adhesion molecule expression may compromise formation of a normal placenta, thereby resulting in adverse outcomes. This study is a prospective, case-control comparison of Israeli mother-neonate (singletons) pairs of complicated pregnancies: 33 preterm deliveries (PTDs), 20 preeclampsia (PE), and 28 idiopathic small for gestational age neonates (SGA) versus 98 pairs of uncomplicated singleton deliveries. PCR amplification identified polymorphisms in the 5′ regulatory region of the PAR1 gene at [−1426(C/T)], insertion at [−506 (I/D)], and IVS at [−14 (A/T)]. We found that 15.2% mothers with PTD were heterozygous for [−1426] versus 3% in uncomplicated deliveries; however, maternal allele frequency was not significantly different between pregnancies complicated by PE or SGA versus uncomplicated pregnancies. Maternal allele frequencies for [−506] and [−14] polymorphisms were not significantly different between any of the study groups compared to the uncomplicated group. Haplotype analysis recapitulated the genotype pattern. Maternal homozygous allele frequency for each of the polymorphic variants was low (

In young women treated for intermediate-high-grade non-Hodgkin's lymphoma with CHOP (cyclophosphamide, adriamycin, oncovine and prednisone), there is insufficient data concerning gonadotoxicity or the need for fertility-preserving measures. The aim of the present study was to evaluate the fertility status in the first complete remission of women who were treated for aggressive non-Hodgkin's lymphoma. A cohort of 36 women with aggressive non-Hodgkin's lymphoma in first remission, who were treated in five university-affiliated hospitals in Israel, was evaluated. All women were aged younger than 40 years at diagnosis and received frontline protocols, including cyclophosphamide and adriamycin, mostly CHOP. Menstrual cycle characteristics, as well as pregnancies before the diagnosis, during treatment and in first complete remission, were evaluated. The patients' mean age at the diagnosis was 28 +/- 7 years (range 17 - 40 years). All patients were treated with chemotherapy, although 10 patients received additional radiotherapy. Follow-up time at first complete remission was 84 +/- 48 months. Before diagnosis, all patients had menstrual cycles, which were regular in 31 (86%). Three patients received gonadtropin-releasing hormone analogs, whereas nine received contraceptive pills together with cytotoxic treatment. During treatment, 18 patients (50%) had amenorrhea, six (17%) had irregular menstrual cycles, and 12 (33%) continued their regular cycles. All but two women resumed menses in the first complete remission, and these were regular in 22 (61%) patients. In 63% of patients, the menstrual cycle recovered within 3 months of the discontinuation of chemotherapy. Eighteen patients (50%) became pregnant during the first complete remission. There was no significant difference between those patients who received fertility-preserving measures versus the remainder concerning regular menstrual cycles recovery or pregnancies. The two patients who developed amenorrhea were 40 years old at the time of diagnosis. In conclusion, the rate of gonadal dysfunction is very low among young, CHOP treated, non-Hodgkin's lymphoma female patients. Fertility-preserving techniques are not needed for women aged younger than 40 years and should probably be reserved for those who are at high risk for gonadal toxicity.

section (TOLAC)-is it really that dangerous? Shunit Armon, Aharon Tevet, Tehila Avitan, Hadar Rosen, Surina Grisaro-Granovsky, Arnon Samueloff Shaare Zedek Medical Center, Obstetrics and Gynecology, Jerusalem, Israel, Shaare Zedek Medical Center, Obstetrics and Gynecology, Jerusalem, Israel, Shaare Zedek MC, Affiliated to the Hebrew University Medical School, Obstetrics and Gynecology, Jerusalem, Israel OBJECTIVE: To evaluate the safety of oxytocin during TOLAC. STUDY DESIGN: Prospective historical cohort trial in a tertiary center, May 2005-May 2011. All women, with a history of a single low transverse cesarean section (LSTCS) attempting vaginal delivery were included. Multifetal gestation, noncephalic presentations, known fetal malformations and intrauterine death were excluded. A strict protocol was implemented for Oxytocin use during induction/augmentation of labor. The protocol allowed use of oxytocin at an initial dose of 0.5mU/min, with increments of 0.5mU/min at 20’ intervals. Continuous FHR monitoring was mandated. Oxytocin was withheld from grandmultiparas and women with uterine malformations. Statistical analysis:descriptive,t test, chi square, Pearson coefficient, Fishers exact test,logistic regression model. RESULTS: During the study period 73,881 deliveries were attended, 4806 met entry criteria and analyzed according to oxytocin use. Group 1-665(13.8%) women treated with oxytocin (mean duration of 267 min). Group 2-4141 (86.2%) women not treated with oxytocin. Groups were comparable for maternal age, gestational age and epidural anesthesia. The overall rate of uterine rupture (UR) was .3%, and did not differ between the groups (p .42) nor did the finding of scar dehiscence. Grandmultiparas did not have a higher UR rate (p .76). Duration of oxytocin use did not effect the rate of UR (P .09). Women in group 1 were more likely to be delivered by CS or Vaccum. The incidence of adverse outcomes mainly post partum hemorrhage (PPH) and febrile morbidity was higher in the oxytocin group, this could be explained by the higher CS rate and oxytocin use. There were no maternal deaths. Neonatal outcomes: there was no difference between the groups regarding NICU admission. Surprisingly, The incidence of 5 apgar score 7 was higher among neonates from the “no oxytocin” group, and did not change after adjustment for gestational age. One neonatal death was recorded (group 1). CONCLUSION: Use of oxytocin under a strict protocol does not pose an additional risk of uterine rupture during TOLAC.

CESAREAN FOR NEONATE; SUPERIOR TO CESAREAN FOR MOTHER RACHEL MICHAELSON-COHEN, SORINA GRISARU-GRANOVSKY, TAMAR HALEVY-SHALEM, AHARON TEVET, ARNON SAMUELOFF, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel OBJECTIVE: Planned cesarean section (CS) has become the customary approach for delivery of the fetus in breech presentation at term. We aimed to assess whether the increase in the CS rate has improved neonatal outcome without compromising maternal outcome. STUDY DESIGN: We compared breech delivery prior to and after the Term Breech Trial (1996, 2005 respectively). During both periods vaginal delivery (VD) was managed by our strict dynamic protocol, which includes selection criteria (EFW 2500-3800g, flexion of fetal head, frank/complete breech presentation, adequate maternal pelvis, cooperative patient, lack of perinatal complications) with reevaluation during each stage (adequate labor progression, normal fetal monitoring). Primary outcomes were perinatal mortality or serious morbidity, and maternal mortality or serious morbidity. Analysis was by intention to treat. RESULTS: In our tertiary center there were 5,814 deliveries in 1996, 178 (3.1%) breech presentation; 115 (64.6%) were planned CS and 63 (35.4%) were planned VD. There were 10,621 deliveries in 2005, 292 (2.7%) were breech presentation; 264(90.4%) were planned CS; 28(9.6%) were planned VD. Thus, planned VD decreased from 35.4% to 9.6%. 98.3% vs. 98.9% of planned CS were delivered by CS in 1996 and 2005, respectively. 68.3% vs. 32.1% of those with planned VD were delivered vaginally in the first and second study period, respectively. Perinatal outcome did not differ between the two periods. There were no low Apgar scores, major perinatal trauma cases, extended NICU admissions or perinatal deaths. Maternal morbidity was significantly higher in the later period, with an overall 16.4% increase in any adverse outcome (extended hospitalization length, postpartum fever, wound infection, blood transfusion, pneumonia, deep vein thrombosis and intestinal obstruction increased by 7.1%, 5.0%, 1.5%, 1.2%, 0.8%, 0.4% and 0.4%, respectively, P 0.05 ). CONCLUSION: The maternal risks of planned CS for breech presentation at term are unwarranted given comparable neonatal outcome when delivering vaginally by a strict protocol.