Intra-vaginal prostaglandin E2 versus double-balloon catheter for labor induction in term oligohydramnios.

OBJECTIVE: Compare mechanical and pharmacological ripening for patients with oligohydramnios at term. STUDY DESIGN: Fifty-two patients with oligohydramnios ⩽ 5 cm and Bishop score ⩽ 6 were randomized for labor induction with a vaginal insert containing 10 mg timed-release dinoprostone (PGE2) or double-balloon catheter. The primary outcome was time from induction to active labor. Time to labor, neonatal outcomes and maternal satisfaction were also compared. RESULT: Baseline characteristics were similar. Time from induction to active labor (13 with PGE2 vs 19.5 h with double-balloon catheter; P = 0.243) was comparable, with no differences in cesarean rates (15.4 vs 7.7%; P = 0.668) or neonatal outcomes. The PGE2 group had higher incidence of early device removal (76.9 vs 26.9%; P = 0.0001), mostly because of active labor or non-reassuring fetal heart rate. Fewer PGE2 patients required oxytocin augmentation for labor induction (53.8 vs 84.6% P = 0.034). Time to delivery was significantly shorter with PGE2 (16 vs 20.5 h; P = 0. 045). CONCLUSION: Intravaginal PGE2 and double-balloon catheter are comparable methods for cervical ripening in term pregnancies with oligohydramnios.

The effect of heat shock protein 27 on extravillous trophoblast differentiation and on eukaryotic translation initiation factor 4E expression.

Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.

The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function.

UNLABELLED: Extravillous trophoblast cells (EVT) are major players in placental implantation. They differentiate in the villous cell column, invade to the uterus and remodel the uterine spiral arteries. Trophoblast and tumor cells have similar invasion mechanisms, share similar biochemical mediators (e.g. c-myc, MMP9) and growth-factors (e.g. VEGF). The mRNA of these proteins has extremely structured 5-UTR and their translation is highly dependent on eukaryotic-translation-initiation-factor-4E (eIF4E). Cancer cells have elevated eIF4E and are more vulnerable to its silencing than normal cells. We speculated that like cancer, trophoblast function is highly eIF4E dependent. OBJECTIVE: Analyze eIF4E involvement in EVT differentiation and function. STUDY DESIGN: EIF4E levels were assessed in first-trimester human placentae and in placental explants before and after EVT differentiation. The effect of eIF4E knockdown (siRNA, ribavirin) on the phenotype of placental explant and EVT cell lines (HTR-8/SVNEO) was evaluated. Tested parameters included eIF4E and its target levels, migration, invasion, cell death, cell cycle and cell count. RESULTS: High eIF4E levels were found in cytotrophoblast and especially EVT cells during their differentiation in the villi, compared to other placental cell types. EIF4E silencing increased cell death and cell cycle arrest in placental explants and HTR-8/SVNEO cells. Although it induced EVT outgrowth in the placental explants, it reduced HTR-8/SVNEO motility, reflecting the importance of using ex vivo models that include an intact placental microenvironment in its original architecture. CONCLUSIONS: Our results suggest that eIF4E prevents final EVT differentiation and supports placental cell proliferation and survival. A balance between cell proliferation and differentiation is crucial for placental development and implantation.

Suspected macrosomia? Better not tell.

OBJECTIVE: To evaluate the management policy of delivery in a suspected macrosomic fetus and to describe the outcome of this policy. STUDY DESIGN: For this prospective observational study we followed the management by reviewing the medical records of 145 women and their infants. The study population included women at term admitted to the obstetrics department with suspected macrosomic infants, as was diagnosed by an obstetrician and/or by fetal sonographic weight estimation of > or =4,000 g. The comparison group (n = 5,943) consisted of all women who gave birth during the data collection period. RESULTS: Induction of labor and cesarean delivery rates in the macrosomic pregnancies (actual birth weight >4,000 g) of the study group were significantly higher when compared with the macrosomic pregnancies of the comparison group. When comparing the non-macrosomic to the macrosomic pregnancies (actual birth weight 4,000 g) of the study group no significant difference was demonstrated regarding maternal or infant complications. The sensitivity, specificity and positive predictive value of the methods used for detecting macrosomia were 21.6, 98.6 and 43.5%, respectively. CONCLUSION: Our ability to predict macrosomia is poor. Our management policy of suspected macrosomic pregnancies raises induction of labor and cesarean delivery rates without improving maternal or fetal outcome.