Clinical impact of the disposable ventouse iCup® versus a metallic vacuum cup: a multicenter randomized controlled trial.

BACKGROUND: Assisted vaginal delivery by vacuum extraction is frequent. Metallic resterilizible metallic vacuum cups have been routinely used in France. In the last few years a new disposable semi-soft vacuum extraction cup, the iCup, has been introduced. Our objective was to compare maternal and new-born outcomes between this disposable cup and the commonly used Drapier-Faure metallic cup. METHODS: This was a multicenter prospective randomized controlled open clinical trial performed in the maternity units of five university hospitals and one community hospital in France from October 2009 to February 2013. We included consecutive eligible women with a singleton gestation of at least 37 weeks who required vacuum assisted delivery. Women were randomized to vacuum extraction using the iCup or usual Drapier-Faure metallic cup. The primary outcome was a composite criterion including both the risk of cup dysfunction and the most frequent maternal and neonatal harms: the use of other instruments after attempted vacuum extraction, caesarean section after attempted vacuum extraction, three detachments of the cup, caput succedaneum, cephalohaematoma, episiotomy and perineal tears. RESULTS: 335 women were randomized to the disposable cup and 333 to extraction using the metallic cup. There was no significant difference between the two groups for the primary outcome. However, failed instrumental delivery was more frequent in the disposable cup group, mainly due to detachment: 35.6 % vs 7.1 %, p < 0.0001. Conversely, perineal tears were more frequent in the metallic cup group, especially third or fourth grade perineal tears: 1.7 % versus 5.0 %, p = 0.003. There were no significant differences between the two groups concerning post-partum haemorrhage, transfer to a neonatal intensive care unit (NICU) or serious adverse events. CONCLUSIONS: While the disposable cup had more detachments and extraction failures than the standard metallic cup, this innovative disposable device had the advantage of fewer perineal injuries. TRIAL REGISTRATION: www.clinicaltrials.gov : NCT01058200 on Jan. 27 2010.

Urinary incontinence 4 and 12 years after first delivery: risk factors associated with prevalence, incidence, remission, and persistence in a cohort of 236 women.

AIMS: Our aim was to study risk factors associated with prevalence, incidence, and remission of UI 4 and 12 years after first delivery. METHODS: Seven hundred seventy-four nulliparous women who gave birth in 1996 in two French maternity units at term received a questionnaire about their urinary symptoms in 2000 and again in 2008. Two hundred thirty-six women returned a questionnaire about UI 4 and 12 years after first delivery. Four groups of women were built: (A) women continent 4 and 12 years after first delivery; (B) women continent at 4 and incontinent at 12 years; (C) women incontinent at 4 and continent at 12 years; and (D) women incontinent at 4 and 12 years. Multivariate logistic regressions were used to determine risk factors of UI prevalence (groups B + D vs. A + C), incidence (B vs. A), remission (C vs. D), and onset of UI (D vs. B) RESULTS: Factors associated with UI 12 years after first pregnancy were: BMI (OR = 1.17 [95%CI: 1.04-1.32], by 1 kg/m(2) ) and increasing BMI (1.43 [1.19-1.73]), first child's weight (1.08 [1.001-1.16], by 100 g) and UI during first pregnancy (3.77 [1.83-7.76]). Factors associated with UI incidence were age at first delivery (0.86 [0.75-0.98]) and high BMI (1.24 [1.05-1.45]). Increasing BMI, UI during first pregnancy, and heavy first child reduce the likelihood of UI remission (0.37 [0.20-0.68], 0.11 [0.02-0.63], and 0.73[0.59-0.91], respectively). CONCLUSIONS: UI during first pregnancy could be indicative of individual susceptibility to UI. Obesity appears to be a modifiable factor for remission of UI in women.

Instrumental delivery: clinical practice guidelines from the French College of Gynaecologists and Obstetricians.

Routine use of a partograph is associated with a reduction in the use of forceps, but is not associated with a reduction in the use of vacuum extraction (Level A). Early artificial rupture of the membranes, associated with oxytocin perfusion, does not reduce the number of operative vaginal deliveries (Level A), but does increase the rate of fetal heart rate abnormalities (Level B). Early correction of lack of progress in dilatation by oxytocin perfusion can reduce the number of operative vaginal deliveries (Level B). The use of low-concentration epidural infusions of bupivacaine potentiated by morphinomimetics reduces the number of operative interventions compared with larger doses (Level A). Placement of an epidural before 3-cm dilatation does not increase the number of operative vaginal deliveries (Level A). Posterior positions of the fetus result in more operative vaginal deliveries (Level B). Manual rotation of the fetus from a posterior position to an anterior position may reduce the number of operative deliveries (Level C). Walking during labour is not associated with a reduction in the number of operative vaginal deliveries (Level A). Continuous support of the parturient by a midwife or partner/family member during labour reduces the number of operative vaginal deliveries (Level A). Under epidural analgesia, delayed pushing (2h after full dilatation) reduces the number of difficult operative vaginal deliveries (Level A). Ultrasound is recommended if there is any clinical doubt about the presentation of the fetus (Level B). The available scientific data are insufficient to contra-indicate attempted midoperative delivery (professional consensus). The duration of the operative intervention is slightly shorter with forceps than with a vacuum extractor (Level C). Nonetheless, the urgency of operative delivery is not a reason to choose one instrument over another (professional consensus). The cup-shaped vacuum extractor seems to be the instrument of choice for operative deliveries of fetuses in a cephalic transverse position, and may also be preferred for fetuses in a posterior position (professional consensus). Vacuum extraction deliveries fail more often than forceps deliveries (Level B). Overall, immediate maternal complications are more common for forceps deliveries than vacuum extraction deliveries (Level B). Compared with forceps, operative vaginal delivery using a vacuum extractor appears to reduce the number of episiotomies (Level B), first- and second-degree perineal lesions, and damage to the anal sphincter (Level B). Among the long-term complications, the rate of urinary incontinence is similar following forceps, vacuum extraction and spontaneous vaginal deliveries (Level B). Anal incontinence is more common following forceps delivery (Level B). Persistent anal incontinence has a similar prevalence regardless of the mode of delivery (caesarean or vaginal, instrumental or non-instrumental), suggesting the involvement of other factors (Level B). Rates of immediate neonatal mortality and morbidity are similar for forceps and vacuum extraction deliveries (Level B). It appears that difficult instrumental delivery may lead to psychological sequelae that may result in a decision not to have more children (Level C). The rates of neonatal convulsions, intracranial haemorrhage and jaundice do not differ between forceps and vacuum extraction deliveries (Levels B and C). Rapid sequence induction with a Sellick manoeuvre (pressure to the cricoid cartilage) and tracheal intubation with a balloon catheter is recommended for any general anaesthesia (Level B). Training must ensure that obstetricians can identify indications and contra-indications, choose the appropriate instrument, use the instruments correctly, and know the principles of quality control applied to operative vaginal delivery. Nowadays, traditional training can be accompanied by simulations. Training should be individualized and extended for some students.

Transvaginal mesh repair of pelvic organ prolapse by the transobturator-infracoccygeal hammock technique: long-term anatomical and functional outcomes.

AIMS: To evaluate long-term anatomical and functional outcomes of the transobturator-infracoccygeal hammock repair for complex genital prolapse with a porcine collagen-coated polypropylene mesh. METHODS: A prospective observational study comparing pre- and postoperative outcomes, using pelvic organ prolapse quantification (POP-Q) measurements, pelvic floor distress inventory (PFDI), and pelvic floor impact questionnaire (PFIQ) scores. RESULTS: One hundred fourteen women with recurrent, advanced, or posthysterectomy genital prolapse were enrolled. During follow-up (median value 57 months), 101 patients were available for assessment. Overall anatomical success rate was 96%, with significant improvement in quality-of-life. Three patients experienced symptomatic recurrent posterior prolapse. Seven had persistent stress urinary incontinence. Mesh exposure occurred in 6.9% of cases, including an infected hematoma that required partial excision of the mesh. No severe adverse event or change in sexual function was observed. CONCLUSIONS: The transobturator-infracoccygeal hammock is well tolerated with effective long-term anatomical and functional results for complex genital prolapse. In our experience and compared to the data of the literature, the use of collagen-coated versus uncoated polypropylene meshes seems to decrease local morbidity.

Mid-term outcome of laparoscopic sacrocolpopexy with anterior and posterior polyester mesh for treatment of genito-urinary prolapse.

OBJECTIVES: To evaluate the anatomical and functional outcomes of laparoscopic sacrocolpopexy using an anterior and a posterior polyester mesh, for the cure of genital prolapse at one year or longer. STUDY DESIGN: This is a consecutive 5 year prospective observational study in which 119 patients presented with at least a Stage 2 apical prolapse, with an anterior or a posterior vaginal wall prolapse, who underwent a double sacrocolpopexy. Two large pore size (≥ 1mm) heavyweight (115 g/m(2)) multifilaments of polyester prostheses (Parietex Prosup PAC/GK 06, Sofradim-Covidien) were exclusively used for this technique. The prostheses were fixed on the levator ani muscles, the vagina and the sacrum with permanent extracorporeal laparoscopic sutures. Pre- and post-operative data referring to international pelvic organ prolapse quantitation classification (POP-Q), scores of quality of life and sexuality (French equivalent of the Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ) and Pelvic organ prolapse-urinary Incontinence-Sexual Questionnaire (PISQ-12)) were compared. RESULTS: With a mean follow-up of 34 months, 116 patients were accessible for evaluation. For these patients, the anatomical success rates (Stage 0 or 1) on the apical, anterior or posterior compartments were respectively, 97%, 89% and 98%. On the functional level, all the scores of quality of life and sexuality were improved. CONCLUSIONS: This study confirms the effectiveness of laparoscopic sacrocolpopexy for the repair of the apical compartment prolapse. It also shows its effectiveness for the anterior compartment repair when the cystocele is moderate and limited to a median defect. In our experience, laparoscopic sacrocolpopexy with heavyweight polyester prosthesis is an effective treatment of the posterior defect.

Is a planned cesarean necessary in twin pregnancies?

OBJECTIVE: Evaluation of elective cesarean section for twin delivery as a standard of care. DESIGN: Historical cohort in a national database (2 597 twin pregnancies). SETTING: France. SAMPLE: Twins with first child in cephalic presentation. METHODS: Decision analysis. MAIN OUTCOME MEASURES: All neonatal complications, i.e. death, whether intrapartum or in the delivery room or the immediate postpartum period, or neonatal transfer to intensive (or special) care, or trauma, of one or both twins. RESULTS: When we focused on neonatal complications for either or both twins, the strategy of planned vaginal delivery was preferable; the weight of its decision tree branch was lower than that for planned cesarean (26.5 vs. 31.7). If only twin 2 was considered, vaginal delivery was also preferred (weight of vaginal delivery=27.6 vs. 32.7 for planned cesarean). As long as the morbidity and mortality of twin 1 or twin 2 or both during a cesarean for twin 2 in the case of planned vaginal delivery does not exceed 31.5%, all else being equal, vaginal delivery should be preferred to a planned cesarean for twin 1 and twin 2. The two-variable sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The results of our study do not support a policy of planned cesarean delivery for twin pregnancies at and after 34 weeks of gestation. LEVEL OF EVIDENCE: II.

Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells.

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) also called prokineticin (PK1), has been identified and linked to several biological processes including angiogenesis. EG-VEGF is abundantly expressed in the highest vascularized organ, the human placenta. Here we characterized its angiogenic effect using different experimental procedures. Immunohistochemistry was used to localize EG-VEGF receptors (PROKR1 and PROKR2) in placental and umbilical cord tissue. Primary microvascular placental endothelial cell (HPEC) and umbilical vein-derived macrovascular EC (HUVEC) were used to assess its effects on proliferation, migration, cell survival, pseudovascular organization, spheroid sprouting, permeability and paracellular transport. siRNA and neutralizing antibody strategies were used to differentiate PROKR1- from PROKR2-mediated effects. Our results show that 1) HPEC and HUVEC express both types of receptors 2) EG-VEGF stimulates HPEC's proliferation, migration and survival, but increases only survival in HUVECs. and 3) EG-VEGF was more potent than VEGF in stimulating HPEC sprout formation, pseudovascular organization, and it significantly increases HPEC permeability and paracellular transport. More importantly, we demonstrated that PROKR1 mediates EG-VEGF angiogenic effects, whereas PROKR2 mediates cellular permeability. Altogether, these data characterized angiogenic processes mediated by EG-VEGF, depicted a new angiogenic factor in the placenta, and suggest a novel view of the regulation of angiogenesis in placental pathologies.

The motor protein myosin-X transports VE-cadherin along filopodia to allow the formation of early endothelial cell-cell contacts.

Vascular endothelium (VE), the monolayer of endothelial cells that lines the vascular tree, undergoes damage at the basis of some vascular diseases. Its integrity is maintained by VE-cadherin, an adhesive receptor localized at cell-cell junctions. Here, we show that VE-cadherin is also located at the tip and along filopodia in sparse or subconfluent endothelial cells. We observed that VE-cadherin navigates along intrafilopodial actin filaments. We found that the actin motor protein myosin-X is colocalized and moves synchronously with filopodial VE-cadherin. Immunoprecipitation and pulldown assays confirmed that myosin-X is directly associated with the VE-cadherin complex. Furthermore, expression of a dominant-negative mutant of myosin-X revealed that myosin-X is required for VE-cadherin export to cell edges and filopodia. These features indicate that myosin-X establishes a link between the actin cytoskeleton and VE-cadherin, thereby allowing VE-cadherin transportation along intrafilopodial actin cables. In conclusion, we propose that VE-cadherin trafficking along filopodia using myosin-X motor protein is a prerequisite for cell-cell junction formation. This mechanism may have functional consequences for endothelium repair in pathological settings.

Role of EG-VEGF in human placentation: Physiological and pathological implications.

Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.

Prenatal diagnosis of achondroplasia: new specific signs.

BACKGROUND: Achondroplasia is one of the most common forms of short limb dwarfism. It is usually suspected on third trimester routine ultrasound because of very shortened long bones. We have described two new prenatal sonographic signs of achondroplasia visible at the proximal femoral metaphysis. METHODS: Over 5 years, five fetuses were diagnosed with achondroplasia at the Grenoble Prenatal Diagnosis Centre. Ultrasound and tomographic examinations were performed by specialists. To study the proximal metaphysis, the ultrasound transducer was positioned at a 45 degree angle to the diaphyseal axis. Postnatal diagnosis was confirmed. RESULTS: On computed tomography and postnatal X-ray, proximal femoral metaphysis appeared rounded, with poor, uneven ossification. Connexion to diaphysis was abnormal, with relative overgrowth of the periosteum, creating a new diagnostic sign that we called the 'collar hoop' sign. On ultrasound, all fetuses had a very rounded metaphyseal-epiphyseal interface, with an angle connexion to diaphysis wider than expected. The 'collar hoop' sign was obvious on four of the fetuses. During the same period, proximal femoral metaphyses appeared normal in 653 healthy fetuses, suggesting high specificity of those two new signs. CONCLUSION: Metaphysis examination is recommended if fetal femur length measures below the fifth percentile, as normal aspect may rule out achondroplasia.

Contribution of annexin 2 to the architecture of mature endothelial adherens junctions.

The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.

Value of Toxoplasma gondii detection in one hundred thirty-three placentas for the diagnosis of congenital toxoplasmosis.

The placenta examination by polymerase chain reaction and mouse inoculation increased the sensitivity of the diagnosis of congenital toxoplasmosis at birth from 60% (use of serologic techniques on the newborn's blood only) to 75% (both serologic techniques and placental analysis). The specificity of Toxoplasma gondii detection in the placenta was 94.7%.

[Management of twin pregnancy]. / Organisation pratique du suivi des grossesses gémellaires.

The epidemic of multiple pregnancies continues albeit in a different form with twin pregnancies predominating. Determination of chorionicity is the key to management and regular monitoring by ultrasound is a hallmark of quality care. All multiple pregnancies should be offered first trimester screening by nuchal translucency for aneuploidy. Monochorial twins should be scanned at fortnightly intervals to allow complications such as twin-twin transfusion or IUGR to be detected and referral made to a fetal medicine centre.

[Twin delivery]. / Accouchement des grossesses gémellaires.

The number of twin pregnancies is still increasing. This should not be assessed only as therapeutic success but also as complex obstetrical challenges. The main difficulties encountered are dystocic presentations, dystocic labours, and cord prolapses. Specific multiple pregnancy dystocias as chin-to-chin interlocking twins and conjoined twins are very rare. Twin delivery is substantially worse when compared with singleton delivery, with increased morbidity and mortality principally involving the second twin. Labour induction is possible, and should be indicated between the 38th and 39th weeks of gestation. Caesarean section should be done easily, especially in case of prematurity or in case of breech presentation for the first twin. Excepting these cases and the usual caesarean section indications, there is no demonstrated superiority of the caesarean section delivery compared to the vaginal delivery. When needed, internal version and/or breech extraction should be done with intact membranes. Active management of the third stage is necessary, due to uterine surdistension easily leading to uterine atonia.

The complex relationship between smoking in pregnancy and very preterm delivery. Results of the Epipage study.

OBJECTIVE: To assess the relationship between cigarette smoking during pregnancy and very preterm births, according to the main mechanisms of preterm birth. DESIGN: Case-control study (the French Epipage study). SETTING: Regionally defined population of births in France. POPULATION: Eight hundred and sixty-four very preterm live-born singletons (between 27 and 32 completed weeks of gestation) and 567 unmatched full-term controls. METHODS: Data from the French Epipage study were analysed using a polytomous logistic regression model to control for social and demographic characteristics, pre-pregnancy body mass index and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, premature rupture of membranes, spontaneous preterm labour and other miscellaneous mechanisms. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth for low to moderate (1-9 cigarettes/day) and heavy (>/=10 cigarettes/day) maternal smoking in pregnancy, estimated according to the main mechanisms leading to preterm birth. RESULTS: Smokers were more likely to give birth to very preterm infants than non-smokers [adjusted odds ratio (aOR) 1.7, 95% confidence interval (CI) 1.3-2.2]. Heavy smoking significantly reduced the risk of very preterm birth due to gestational hypertension (aOR 0.5, 95% CI 0.3-1.0), whereas both low to moderate and heavy smoking increased the risk of very preterm birth due to all other mechanisms (aOR between 1.6 and 2.8). CONCLUSION: These data from the Epipage study show that maternal smoking during pregnancy is a risk factor for very preterm birth. The impact of maternal smoking on very preterm birth appears to be complex: it lowers the risk of very preterm birth due to gestational hypertension, but increases the risk of very preterm birth due to other mechanisms. These findings might explain why maternal smoking is more closely related to preterm birth among multiparous women than among nulliparous women.

Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study.

Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high-grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LGSIL) cytology, and infected or not by high-risk (HR) HPV tested by Hybrid Capture II. Women were followed up every 6 months for a median period of 22 months. Among the HR-HPV-positive women at entry, more than half cleared their virus in 7.5 months; the clearance rate was greater for low viral loads than for high loads and also was higher in women with an initial ASCUS/LGSIL smear than in women with normal cytology. The incidence of cytologic abnormalities strongly depended on baseline viral load and HR-HPV persistence. Maintenance of cytologic abnormalities was associated with the outcome of HR-HPV status (negative or =100 pg/mL). Conversely, women who were consistently HR-HPV negative or transiently HR-HPV positive, whatever the cytology at baseline was, did not develop CIN2/3+ during follow-up. Age seemed to affect only the rate of incident HR-HPV infection. In conclusion, our data suggest that women repeatedly tested positive for HR-HPV are at risk of developing CIN2/3+, even when initial cytology is normal. A high viral load could be used as a short-term marker of progression toward precancerous lesions, although lower load does not inevitably exclude progressive disease.