Essure Permanent Birth Control, Effectiveness and Safety: An Italian 11-Year Survey.

STUDY OBJECTIVE: To describe safety, tolerability, and effectiveness results through a minimum 2-year follow-up of patients who underwent permanent sterilization with the Essure insert. DESIGN: A retrospective multicenter study (Canadian Task Force classification II2). SETTING: Seven general hospitals and 4 clinical teaching centers in Italy. PATIENTS: A total of 1968 women, mean age 39.5 years (range, 23-48 years) who underwent office hysteroscopic sterilization using the Essure insert between April 1, 2003, and December 30, 2014. INTERVENTION: The women underwent office hysteroscopic bilateral Essure insert placement, with satisfactory device location and tube occlusion based on hysterosalpingography or hysterosalpingo-contrast sonography (HyCoSy). MEASUREMENTS AND MAIN RESULTS: Placement rate, successful bilateral tubal occlusion, perioperative adverse events, early postoperative (during the first 3 months of follow-up), and late complications were evaluated. Satisfactory insertion was accomplished in 97.2% of women and, in 4, perforation and 1 expulsion were detected during hysterosalpingography. Three unintended pregnancies occurred before the 3-month confirmation test. Two pregnancies were reported among women relying on the Essure inserts. Postprocedure pain was minimal and brief; in 9 women, pelvic pain became intractable, necessitating removal of the devices via laparoscopy. On telephone interviews, overall satisfaction was rated as "very satisfied" by the majority of women (97.6%), and no long-term adverse events were reported. CONCLUSION: The findings from this extended Italian survey further support the effectiveness, tolerability, and satisfaction of Essure hysteroscopic sterilization when motivated women are selected and well informed of the potential risks of the device. Moreover, the results do not demonstrate an increased incidence of complications and pregnancies associated with long-term Essure use. Patients with a known hypersensitivity to nickel may be less suitable candidates for the Essure insert.

Identification and characterization of cancer stem cells from head and neck squamous cell carcinoma cell lines.

BACKGROUND/AIMS: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. METHODS: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. RESULTS: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. CONCLUSION: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.

Maternal predictors of intrauterine growth restriction.

PURPOSE OF REVIEW: Intrauterine growth restriction (IUGR) occurs when fetal growth rate falls below the genetic potential and affects a significant number of pregnancies, but still no therapy has been developed for this pregnancy disease. This article reviews the most recent findings concerning maternal characteristics and behaviours predisposing to IUGR as well as maternal early markers of the disease. A comprehensive understanding of factors associated with IUGR will help in providing important tools for preventing and understanding adverse outcomes. RECENT FINDINGS: Maternal nutritional status, diet and exposure to environmental factors are increasingly acknowledged as potential factors affecting fetal growth both by altering nutrient availability to the fetus and by modulating placental gene expression, thus modifying placental function. SUMMARY: Assessing nutritional and environmental factors associated with IUGR, and the molecular mechanisms by which they may have a role in the disease onset, is necessary to provide comprehensive and common guidelines for maternal care and recommended behaviours. Moreover, maternal genetic predispositions and early serum markers may allow a better and more specific monitoring of high risk pregnancies, optimizing the timing of delivery.

Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction.

Unexplained intrauterine growth restriction of the fetus (IUGR) results from impaired placental development, frequently associated with maternal malperfusion. Some cases are complicated further by preeclampsia (PE+IUGR). Here, we provide the first evidence that placental protein synthesis inhibition and endoplasmic reticulum (ER) stress play key roles in IUGR pathophysiology. Increased phosphorylation of eukaryotic initiation factor 2alpha suggests suppression of translation initiation in IUGR placentas, with a further increase in PE+IUGR cases. Consequently, AKT levels were reduced at the protein, but not mRNA, level. Additionally, levels of other proteins in the AKT-mammalian target of rapamycin pathway were decreased, and there was associated dephosphorylation of 4E-binding protein 1 and activation of glycogen synthase kinase 3beta. Cyclin D1 and the eukaryotic initiation factor 2B epsilon subunit were also down-regulated, providing additional evidence for this placental phenotype. The central role of AKT signaling in placental growth regulation was confirmed in Akt1 null mice, which display IUGR. In addition, we demonstrated ultrastructural and molecular evidence of ER stress in human IUGR and PE+IUGR placentas, providing a potential mechanism for eukaryotic initiation factor 2alpha phosphorylation. In confirmation, induction of low-grade ER stress in trophoblast-like cell lines reduced cellular proliferation. PE+IUGR placentas showed elevated ER stress with the additional expression of the pro-apoptotic protein C/EBP-homologous protein/growth arrest and DNA damage 153. These findings may account for the increased microparticulate placental debris in the maternal circulation of these cases, leading to endothelial cell activation and impairing placental development.

PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction.

Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR). We have evaluated utility and applicability of the PlGF test in a clinical setting of pregnancies at risk of PE or complicated by IUGR in order to assess its relationship with pregnancy outcomes. Seventy-three pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in relation to three categories of plasma PlGF levels: very low (<12 pg/ml), low (12-100 pg/ml) and normal (≥100 pg/ml). Uterine artery Doppler velocimetry (UADV) pulsatility index (PI) was measured in the same patients on the day of maternal sampling. Pregnancies at risk with very low plasma PlGF levels had significantly lower gestational age at delivery than patients with low or normal PlGF. The rate of emergency C-section was significantly higher in the group with PlGF <12 pg/ml. IUGR pregnancies with very low and low PlGF delivered earlier than patients with normal PlGF. All IUGR with very low and low PlGF had UADV PI > 95th percentile. Our data indicate that PlGF may provide useful information to identify fetuses requiring increased surveillance and possibly urgent delivery in pregnancies at risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse pregnancy outcomes that may be secondary to placental insufficiency.

The use of bipolar technology in hysteroscopy.

Bipolar technology was introduced in the hysteroscopic clinical use in 1999, by the design of both loop electrodes addressed to resectoscopic surgery and miniaturized electrodes adaptable to small-size hysteroscopes. The need of an electrolytic solution as distension medium and the spatial relationships between the active and return bipolar electrode avoid, by definition, the risks of severe electrolyte imbalance syndromes and unpredictable electrical burns, sometimes complicating monopolar surgery. The true revolution in the hysteroscopy care has achieved through the availability of mini-hysteroscopes not requiring cervical dilatation, thus limiting uterine wall damages and allowing surgeons to manage several endometrial pathologies by mini-invasive procedures using an effective electrosurgical bipolar instrumentation. Many surgical interventions, traditionally accomplished by the resectoscope in a surgical room theatre, can be now carried out in an outpatient setting without any support from anesthesia. The patients' avoidance of surgical room access and the quick return to daily activities lead to an obvious - but not fully demonstrated - improvement in the medical and social costs associated to outpatient operative hysteroscopy. In the field of resectoscopy, bipolar electrodes are clinically as effective as monopolar devices. Randomized trials showed that bipolar resectoscopic technology prevents the electrolyte imbalance observed after monopolar surgery. However, in daily clinical practice the assumedly safer profile of bipolar with respect to monopolar resectoscopy has not been demonstrated yet.

Sex specific adaptations in placental biometry of overweight and obese women.

INTRODUCTION: Placental biometry at birth has been shown to predict chronic disease in later life. We hypothesized that maternal overweight/obesity, a state of low-grade inflammation and risk factor for adverse pregnancy outcome, could negatively influence placental development and that differences would be sex-specific. METHODS: 696 women (537 normal-weight, NW; 112 overweight, OW; 47 obese, OB) with singleton uncomplicated pregnancies were prospectively enrolled at term delivery. Gestational age, maternal (age, height, pre-pregnancy BMI, gestational weight gain -GWG, hemoglobin, hematocrit and glycemia), fetal (weight, length, ponderal index, cranial circumference) and placental (weight, diameters) data were collected. Placental area, thickness and efficiency (fetal/placental weight ratio, F/P) were calculated. RESULTS: GWG was within standard recommendations in OB, while OW exceeded it. Placental weight was significantly higher in OW versus NW, but not in OB, leading to significantly higher placental thickness and lower F/P in this group. In the total population, a significant interaction effect between maternal BMI and fetal sex on placental weight and efficiency was found. Indeed, differences in placental parameters were present only in female offspring. DISCUSSION: In our population of OW and OB uncomplicated pregnancies only OW women, presenting GWG over standard recommendations, had thicker and less efficient placentas. We also reported different placental adaptation depending on fetal sex, with significant changes only in female fetuses. This may be part of a female-specific strategy aiming to ensure survival if another adverse event occurs. Customized counseling according to maternal BMI and fetal sex should be evaluated in clinical care.

Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension, preeclampsia, intrauterine growth restricted and normal pregnancies.

OBJECTIVE: Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the association between both maternal and fetal HLA-G 14 bp insertion/deletion polymorphism and obstetrical complications. METHODS: Clinical and genetic data of 282 women/fetuses (31 severe PE, 8 mild PE, 46 IUGR, 42 PIH and 155 controls) were analyzed both individually and jointly under a codominant, a dominant and a recessive model. RESULTS: HLA-G 14 bp polymorphism was not associated with obstetrical complications, considering the mother and fetus genotypes both jointly and individually. CONCLUSIONS: With this study we filled several gaps occurring in previous studies: we analyzed a very well-defined population of PE, PIH and IUGR pregnancies, considering both fetal and maternal HLA-G 14 bp polymorphism, individually and jointly. Our findings showed that fetal and maternal HLA-G 14 bp genotypes are not associated with increased risk for the development of obstetrical complications, suggesting that this polymorphism has no immuno-modulatory role in the development of PE, PIH or IUGR.