Vulvovaginal atrophy of menopause and its impact on sexual function in an Italian clinical cohort of post-menopausal women.

The aim of current study was to estimate the impact of vulvovaginal atrophy (VVA) on sexual function in a clinical population of Italian postmenopausal women. Women aged 45-75 years with at least one VVA symptom completed three questionnaires: Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI) and Female Sexual Distress Scale revised (FSDS-R). A gynaecological examination was performed for VVA confirmation. Among the 1,066 evaluable patients, VVA was confirmed in around 90% of the sample. Sexual function impairment was significantly higher in patients with confirmed VVA as observed by significant differences in the sexual function component of the DIVA questionnaire (p = .014), the FSDS-R (p < .0005), and the FSFI (p < .0005), as well as for all the FSFI subdomains: desire (p < .0005), arousal (p < .0005), lubrication (p < .0005), orgasm (p < .0005), satisfaction (p < .0005) and pain (p < .0005). Significant impairment of sexual function was demonstrated in Italian postmenopausal women who were clinically confirmed with signs of VVA through gynaecological examination.IMPACT STATEMENTWhat is already known on this subject: At least half of postmenopausal women report VVA associated symptoms with significant impact on sexual function and ultimately on sexual activity.What the results of this study add: As compared with patients without confirmed VVA, the negative impact on sexual function was significantly higher in patients with confirmed VVA. This difference was observed for the sexual function component (DIVA-C) of the DIVA questionnaire, for the overall FSDS-R result, and for the overall FSFI score, as well as for all the FSFI subdomains (desire, arousal, lubrication, orgasm, satisfaction and pain).What the implications are of these findings for clinical practice and/or further research: An impairment of sexual function is significantly associated with VVA diagnosis in Italian post-menopausal women, especially when diagnosis was objectively confirmed by clinical signs of VVA visible in the gynaecological examination. In addition, this study demonstrates that inquiring about VVA using a structured questionnaire may increase the diagnosis of VVA related changes in sexual function.

Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: (i) examined the cytokine expression profile; (ii) counted AhR-expressing MCs; (iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; (iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); (v) treated ET organ cultures with an AhR antagonist in vitro to measure changes in the cytokine milieu; and (vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors released by MCs on AhR activation. These results suggest a new mechanistic role of MCs in the pathogenesis of endometriosis.

Second trimester maternal plasma and amniotic fluid adipokines in women who will develop gestational diabetes mellitus.

OBJECTIVE: To study the adipokines concentration and glucose homoeostasis in the early-second trimester of women who will develop gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Maternal plasma and fetal amniotic fluid samples were prospectively collected between 2006 and 2007 at the time of mid-trimester amniocentesis. Eight patients found to be affected by GDM were compared with 10 control patients with a normal pregnancy course. Adipokines leptin and adiponectin, as well as insulin and glucose concentration both in amniotic fluid and maternal plasma were compared between cases and controls. HOMA-IR (homeostatic model assessment for insulin resistance) was also calculated both for amniotic fluid and maternal serum. RESULTS: The amniotic fluid adiponectin concentration was higher in women who would develop GDM than in controls (29.9 ng/ml, 95% CI 26.7-49.8 ng/ml, versus 14.9 ng/ml, 95% CI 13.5-18.8 ng/ml), p < 0.05). No difference was shown for leptin both in amniotic fluid and maternal serum. Insulin concentrations in the amniotic fluid were found to be lower in GDM than in controls, while HOMA-IR-index resulted lower in amniotic fluid and higher maternal serum (p < 0.05). CONCLUSIONS: Our data suggests that an earlier alteration in the fetal glucose metabolism will precede the glucose dysmetabolism in pregnancies later complicated by GDM.

Building a Prediction Model for Vacuum-Assisted Operative Vaginal Delivery Risk.

AIM: The objective of this study was to evaluate the risk factors for operative vaginal delivery and to propose a new nomogram for predicting the risk. METHODS: We retrospectively analyzed the data of 1,955 pregnancies that occurred in our clinic between the years 2007 and 2008. Included were singleton pregnancies with labor diagnosis after the 36th gestational week in which spontaneous or operative vaginal deliveries occurred. In this study, the operative delivery was carried out exclusively by vacuum extraction. RESULTS: After univariate analysis and multivariate logistic regression stepwise model selection, maternal age, nulliparity, medically assisted procreation, gestational age at birth, male fetus, epidural analgesia and medical induction of labor were found to be the most predictive variables for operative vaginal delivery. Considering these factors we propose a new nomogram for an objectified determination of the risk of operative vaginal delivery. CONCLUSIONS: The new nomogram we propose could be an important tool for an objectified determination of the risk of operative vaginal delivery by vacuum extraction in individualized patient counseling.

Puerperal ovarian vein thrombosis: two case reports.

Ovarian vein thrombosis (OVT) is an uncommon but potentially serious complication in the early postpartum. Two case studies seem to prove the point: Case 1 A 24-year-old woman was transferred to our hospital with the chief complaint of abdominal pain radiating to the right thigh, vomit, diarrhea, and a slight pyrexia (37.6 °C rectal). Five days earlier, she had a spontaneous vaginal delivery after labor induction. The woman appeared slightly distressed because of pain; vital signs were found to be normal and the CRP elevated (129.9 mg/L). Abdominal examination was remarkable for tenderness by palpation in the right lower quadrant with no rebound tenderness or guarding. Pelvic examination was remarkable for mild right adnexal tenderness. Abdominal-pelvic computer tomography with contrast medium revealed a 2.5-cm OVT having extended into the inferior vena cava for 14 cm with a slight peripheral edema. The patient was treated with nadroparin 0.6 cc (5700 IU) bid and warfarin 5 mg since the attainment of the therapeutic INR range. Case 2 A 31-year-old twin-pregnant woman had an emergency cesarean section at 35 gestational weeks because of hypertension complicated by increased liver enzymes, diuresis contraction, and continuous lower back pain bilaterally radiating to the groins. One day after delivery, CT scan that was performed because of onward anemia showed a pelvic, perihepatic, and perisplenic blood effusion, and a 1-cm right OVT extended to the inferior vena cava below renal veins for 28 mm. She underwent exploratory laparotomy and blood transfusion, and because of respiratory insufficiency she was transferred to a second level center with ICU facility, where she was placed under a suprarenal inferior vena cava filter, and AngioJet Rheolytic Thrombectomy for acute pulmonary embolism was performed.

High placental index and poor pregnancy outcomes: a retrospective study of 18,386 pregnancies.

INTRODUCTION: Our aim was to state the correlation between placental index and pregnancy outcomes or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. MATERIALS AND METHODS: We included in this retrospective study all singleton births in a third level clinic during the period 2001-2011 (n = 18,386). We divided placental index into quartiles and analyzed the differences between the groups in term of pregnancy outcomes. Then, we estimated crude and adjusted odds ratios (ORs) for placental index over the third centile of the distribution to correlate with pregnancy outcomes. We also analyzed the correlation between IVF/ICSI conceived pregnancies and placental index. RESULTS: Poor pregnancy outcomes were overrepresented in the highest quartile of placental index distribution. Thus, placental index was higher in pregnancies characterized by pregnancy-related hypertensive disorders (PRHDs), small for gestational age infants, newborn needing cardiopulmonary resuscitation or hospitalization in neonatal intensive care unit. These findings were independent of maternal age, length of gestation at delivery, IVF/ICSI conception and ethnicity. For IVF/ICSI pregnancies, the OR for being over the third quartile of placental index distribution was 2.01 (CI.95 1.40-2.90) after adjustment for maternal age, length of gestation, ethnicity, birth weight, parity, fetal sex, alteration of glucose metabolism in pregnancy and PRHDs. CONCLUSIONS: We found a high placental index among pregnancies characterized by poor outcomes and conceived by IVF/ICSI.

Retinol binding protein as early marker of fetal growth restriction in first trimester maternal serum.

BACKGROUND: Serum retinol binding protein (RBP4) is the binding protein for retinol, being delivered into the circulation through the carrier protein transthyretin (TTR) together with thyroxin (T4). RBP4 has also been recently indicated as a new adipokine implicated in insulin resistance and metabolism regulation. OBJECTIVE: To investigate the role of RBP4 as early markers of fetal growth restriction (FGR) and preeclampsia (PE) in maternal serum during the first trimester of pregnancy. MATERIALS AND METHODS: Retrospective case control study in patients between the 12th and the 14th week of gestation. RBP4, TTR and T4 concentration was assessed in maternal serum of three groups of women: 15 and 14 patients later developing respectively FGR and PE were compared with 11 patients having a normal pregnancy. RESULTS: All women were Caucasian and the mean maternal age was 33.62 years (±5.50). RBP4 resulted lower in the FGR than in the control group (11.00 versus 16.00 µg/ml, p < 0.05) and than in the PE group (15.00 µg/ml, p = 0.075), both in bivariate and multivariate analysis. No difference was observed in TTR and T4 concentration. CONCLUSIONS: RBP4 seems to play a role as early marker of FGR but not PE in first trimester maternal serum.

First trimester PAPP-A MoM values predictive for breech presentation at term of pregnancy.

INTRODUCTION: Our aim was to state the role of first trimester pregnancy-associated plasma protein A (PAPP-A)-multiple of the median (MoM) value as a predictor for breech presentation at term of pregnancy. MATERIALS AND METHODS: In this retrospective study, we present data for 1100 singleton full-term deliveries that took place in a third-level hospital setting in northeast Italy between January 2004 and July 2007. For each case, PAPP-A, free beta-human chorionic gonadotropin and nuchal translucency were measured during prenatal trisomies screening (between 11 weeks and 13 weeks and 6 d). A wide range of predictive factors for breech presentation at term of pregnancy and other confounding elements were considered. RESULTS: Of the 1100 singleton deliveries at term considered in our study, 40 babies were in breech presentation. Using bivariate analysis and multivariate logistic regression, a lower PAPP-A MoM than 0.63 (first quartile of our distribution) in the first trimester (OR 2.41, CI.95 1.25-4.67), and placental index at term higher than the median value (OR 2.04, CI.95 1.00-4.17) were proven to be associated with breech presentation at term. CONCLUSIONS: A low PAPP-A during the first trimester was a predictive factor for breech presentation at term of pregnancy. Acknowledging and acting on this predictor could enable improved management of breech foetuses in the future.

Surgical treatment of ectopic pregnancy associated with predisposing factors of tuboperitoneal infertility.

OBJECTIVE: We sought to study the advantages of laparoscopic conservative treatment and pelvic reproductive surgery in patients with ectopic pregnancy and predisposing factors of tuboperitoneal infertility. MATERIAL AND METHODS: Patients who had undergone laparoscopic treatment for ectopic pregnancy were considered, with factors for tuboperitoneal infertility, while patients who underwent previous salpingectomy or assisted reproductive technology were excluded. The groups treated by salpingotomy (conservative) or salpingectomy (radical) were compared in terms of spontaneous intrauterine pregnancy rate, cumulative one-year pregnancy rate and recurrence of ectopic pregnancy. We considered patients treated with adhesiolysis, fimbrioplasty, and neosalpingostomy for tubal pathology as part of the fertility surgery group. RESULTS: Among 41 considered patients, 21 (51%) underwent conservative laparoscopic management of ectopic pregnancy. Twenty patients (49%) had salpingectomy. Despite the treatment of tuboperitoneal infertility factors in both groups, the pregnancy rate was significantly higher in the conservative group than in the radical one (76% vs 25%, p < 0.05). The overall cumulative rate of ectopic pregnancy recurrence was 22% and no significant difference was found between conservative and radical treatment (p 0.645). CONCLUSIONS: Salpingotomy should be preferred in all patients with ectopic pregnancy associated with factors of tuboperitoneal infertility. Infertility surgery clearly cannot help patients treated with salpingectomy, who obtain lower spontaneous pregnancy rates than those of the conservative group.

Determinants of ante-partum depression: a multicenter study.

INTRODUCTION: Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. METHODS: Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with "no depression" (scores 0-9), "possible depression" (scores 10-12), "probable depression" (scores 13+) and "probable APD" (scores 15+). RESULTS: The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores.

Plasminogen activator inhibitor-1 gene polymorphisms in pre-eclampsia.

Pre-eclampsia (P-EC) is a multisystem disorder of pregnancy, characterized by new-onset hypertension and proteinuria. Deregulation of the coagulation cascade and hypofibrinolysis appear to play a central role in the development of this disease. After a brief review of the genetic basis of P-EC and the role of genes encoding proteins involved in coagulation, we focus on polymorphisms of the plasminogen activator inhibitor (PAI-1) gene. The most relevant association studies between PAI-1 gene polymorphisms and P-EC are reviewed. Results indicate that the 4G/4G genotype of the -675 4G/5G polymorphism represents a weak risk factor for P-EC.

Expression patterns of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors determined using an endometriosis tissue microarray model.

BACKGROUND: The roles of cell proliferation and genomic instability in endometriosis are highly debated aspects of the pathogenesis of this disease. Aurora A and B kinases play different important roles in cell cycle control and genomic instability and have never been studied in endometriosis. The aim of this study was to compare the expression levels of Aurora kinases, Ki-67 and hormone receptor in endometriotic tissue (ET) and normal endometrium. METHODS: We retrospectively analysed 438 samples obtained from 194 patients affected by endometriosis and 28 samples from 28 patients with normal endometrium, which were all collected by the Pathology Department and Gynecologic Clinic of the University Hospital of Udine. A tissue microarray model was constructed to use immunohistochemistry to analyse the expression of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors in ET and normal endometrium. RESULTS: Aurora A and B kinases were expressed at a very low level in the majority of endometriosis core biopsies. Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors were expressed at a higher level in the proliferative endometrium than in the secretory endometrium and in ovarian and non-ovarian ET (P < 0.05). Additionally, Aurora B kinase, Ki-67 and the estrogen and progesterone receptors were more highly expressed in non-ovarian than ovarian ET (P < 0.05). CONCLUSIONS: Considering the low expression levels of Aurora A and B kinases in the majority of endometriosis core biopsies, the growth and survival of endometrial tissue outside the uterus cannot be explained by deregulation of this pathway. The analysed ectopic endometrium protein expression pattern resembled that of the secretory endometrium, and markers of proliferation and hormone receptors were expressed at lower levels in ovarian than in non-ovarian ET. The low level of hormone receptors and the consequent low levels of proliferation markers in ovarian ETs may be due to down-regulation by the ovary's hormone milieu.

Impact of episiotomy on pelvic floor disorders and their influence on women's wellness after the sixth month postpartum: a retrospective study.

BACKGROUND: The role of episiotomy as a protective factor against pelvic floor disorders postpartum has been debated for many years, but its routine use has been hitherto discouraged in the literature. Comparisons between restrictive and routine use of episiotomy in existent literature, however, fail to include any consideration relating to quality of life. The aim of this study, therefore, is to state the role of episiotomy in preserving the perineum from damage, in order to prevent the influence of pelvic floor disorders on women's psycho-physical wellness after the sixth month postpartum. METHODS: A follow-up telephone interview was performed among 377 primiparous and secondiparous Caucasian women who had a child by spontaneous or operative vaginal delivery in 2006 using a self-created questionnaire and King's Health Questionnaire (KHQ). RESULTS: The mean age at delivery was 35.26 (±4.68) years and episiotomy was performed in 59.2% of women. Multivariate linear regression shows episiotomy associated to higher quality of life after the sixth month postpartum by correlating with inferior values of King's Health Questionnaire (p < 0.05). CONCLUSIONS: Episiotomy appears to be a protective factor for women's wellness. Women who had episiotomy and who experienced perineal symptoms have a better psycho-physical health status in the 12.79 months (±3.3) follow-up.

Menstrual abnormalities and predisposition to pregnancy-related hypertensive disorders: a retrospective study.

OBJECTIVE: Pregnancy-related hypertensive disorders (PRHDs) are a leading cause of maternal and perinatal morbidity and mortality in developed countries. This study investigated a possible association of PRHDs with menstrual abnormalities. MATERIALS AND METHODS: We contacted all women with PRHDs who delivered in our clinic between 2004 and 2007 as well as a random control cohort without pregnancy complications and asked them about their menstrual cycle characteristics. Statistical analyses were performed using R, with significance set at p < 0.05. RESULTS: We collected data for 237 women with normal pregnancies and 255 women with PRHDs, among whom 143 had gestational hypertension and 70 had mild and 41 severe preeclampsia. By monovariate analysis, PRHDs correlated with dysmenorrhoea, hypermenorrhoea and menstrual irregularity (p < 0.05). By multivariate analysis, the occurrence of PRHDs was influenced by dysmenorrhoea and menstrual irregularity (p < 0.05). CONCLUSIONS: PRHDs usually affect women with painful or irregular menstrual cycles, perhaps due to metabolic syndrome or molecular pathways involving vasoactive substances, with clear vascular implications.

Bone ultrasonometry measurements during pregnancy.

PURPOSE: During pregnancy we can have changes of the calcium metabolism that can determine a loss of bone mass. Some studies used single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry, but these exams are inadvisable in pregnancy for the teratogenic effects on the fetus. We used quantitative ultrasonometry (QUS). The aim of this study is to determine prospective changes of bone density with an ultrasonometry measurement during pregnancy in healthy Italian women. METHODS: The study population was represented by 59 pregnant women. Quantitative ultrasonometry measurements were performed at the phalanges during the first, second and third trimester. RESULTS: We found a progressive decrease of bone time transmission (BTT) from the first to the third trimester, while amplitude dependent speed of sound (AD-SoS) remained stable between the first and the second trimester and decreased at the term of pregnancy. The z- and t-scores decreased more during the second and third trimester. CONCLUSIONS: These results show an important reduction in the third trimester of pregnancy, of all ultrasonometry variables and then an increase of remodelling with bone demineralisation in the mother. These results show that there is a different bone metabolism in pregnancy in pluriparous and nulliparous women.

Effect of Online Health Information Seeking on Anxiety in Hospitalized Pregnant Women: Cohort Study.

BACKGROUND: There are approximately 1,000,000 pregnant women at high risk for obstetric complications per year, more than half of whom require hospitalization. OBJECTIVE: The aim of this study was to determine the relation between online health information seeking and anxiety levels in a sample of hospitalized woman with pregnancy-related complications. METHODS: A sample of 105 pregnant women hospitalized in northern Italy, all with an obstetric complication diagnosis, completed different questionnaires: Use of Internet Health-information (UIH) questionnaire about use of the internet, EuroQOL 5 dimensions (EQ-5D) questionnaire on quality of life, State-Trait Anxiety Inventory (STAI) questionnaire measuring general anxiety levels, and a questionnaire about critical events occurring during hospitalization. RESULTS: Overall, 98/105 (93.3%) of the women used the internet at home to obtain nonspecific information about health in general and 95/105 (90.5%) of the women used the internet to specifically search for information related to their obstetric disease. Online health information-seeking behavior substantially decreased the self-reported anxiety levels (P=.008). CONCLUSIONS: Web browsing for health information was associated with anxiety reduction, suggesting that the internet can be a useful instrument in supporting professional intervention to control and possibly reduce discomfort and anxiety for women during complicated pregnancies.

Placental type alkaline phosphatase tissue expression in ovarian serous carcinoma.

OBJECTIVE: To analyze the expression profile of placental type alkaline phosphatase (PLAP), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in serous ovarian cancer and to correlate their expression with the tumor aggressiveness and progression. METHODS: Retrospective study considering a tissue microarray of 82 women affected by ovarian serous cancer. Protein expression was assessed by immunohistochemistry on ovarian serous cancer tissue samples. Immunohistochemical staining was semiquantitatively evaluated as H-score. RESULTS: Median H-score values were lower for PLAP, 1 (IQR 0-4) than CA125, 10 (IQR 6-12) or HE4, 8 (IQR 5-12). Even if PLAP was less expressed in the cells of serous ovarian cancer than CA125 or HE4 it was relatively more expressed in the fourth quartile of its H-score distribution among cases with low CA125 or HE4 expression. Furthermore, PLAP and HE4 high expression resulted to be significantly correlated with a better prognosis. CONCLUSIONS: PLAP could be an additional marker for early detection of serous ovarian carcinoma, together with the established CA125 and HE4. In addition, PLAP expression is correlated with prognosis, giving, in this way, an additional tool for improving treatment approach.

Mismatch repair system in endometriotic tissue and eutopic endometrium of unaffected women.

OBJECTIVE: To test the immunohistochemical staining pattern of some mismatch repair (MMR) system proteins in endometriotic tissue (ET) and eutopic endometrium. METHODS: This was a retrospective study conducted at the Pathology and Obstetrics and Gynecology Departments of the Udine University Hospital. We analyzed 528 samples obtained from 246 patients affected by endometriosis and 71 samples from 71 patients with normal endometrium. A tissue microarray model was used to analyze the immunohistochemical expression of MMR system proteins. RESULTS: Significant loss of MMR proteins was found in the stromal component of ETs. We found MSH2 to be expressed at a higher level than any other MMR system proteins in eutopic endometrium and ETs, to be significantly correlated to Ki-67 expression in both stromal and glandular components of ETs, and to be expressed at a significantly higher level in ETs than in eutopic endometrium. When considering the subgroup of endometriosis with high recurrence rate and glandular cytoplasmic staining for aurora A kinase, we found MMR proteins expressed at a significantly higher level in these ETs than in other ETs and eutopic endometrium of unaffected women. CONCLUSIONS: We found significant loss of MMR proteins (known to be associated with microsatellite instability) in the stromal component of ETs. The group of ETs with glandular cytoplasmic staining for aurora A kinase had higher MMR protein expression, suggesting an increased activity of this system. Our result suggests a novel role of increased MSH2 expression in cellular proliferation of endometriosis.

A novel Q3034R BRCA2 germline mutation identified in a fallopian tube cancer patient.

Fallopian tube cancer (FTC) accounts for 0.1-0.5% of all gynaecological malignancies, so that very few studies have demonstrated a significant linkage between this cancer type and BRCA1/BRCA2 mutations. We report the identification of a novel germline mutation (Q3034R) in BRCA2 gene in a 41-year-old patient. The nucleotide change (CAG > CGG) abolishes a DdeI restriction site, making genotype identification rapid and inexpensive. Our findings support the hypothesis that the primary FTC should be considered, at least in a subset of patients, as a BRCA2-associated tumor. Genetic counselling could result, in these cases, in early diagnosis of genetically predisposed individuals.

Obesity reduces the expression of GLUT4 in the endometrium of normoinsulinemic women affected by the polycystic ovary syndrome.

GLUT4 is the most important glucose transporter in insulin-dependent tissues. A decrease of its expression by the adipocytes was reported in polycystic ovary syndrome (PCOS), regardless of obesity and glucose tolerance. In PCOS, abnormal menstrual cycles, abnormal insulin secretory patterns, and obesity, which are risk factors for endometrial diseases, frequently coexist. The endometrial effects of insulin are direct through specific insulin receptors. However, it is unknown whether the endometrium expresses GLUT4 and can be considered an insulin-regulated tissue. In this study, we investigated this question, and we investigated whether obesity modulates this expression in PCOS normoinsulinemic patients. We assayed GLUT4 in the endometrial samples from 18 normoinsulinemic PCOS patients and 9 controls in the advanced follicular phase of the cycle; 10 patients were lean and 8 obese, and all were aged between 23 and 32 years. Most tissue was immediately frozen for RT-PCR; some tissue was saved for histology and immunohistochemistry. GLUT4 mRNA expression was measured in three samples for every patient and expressed as mean +/- SE of an arbitrary unit. In obese PCOS subjects, endometrial GLUT4 expression was significantly lower than in the lean ones (24.0 +/- 6.8 vs. 65.2 +/- 24.4; P < 0.005) and the controls (53.2 +/- 10.7). Lean PCOS and control subjects showed similar values. GLUT4 immunostaining was strong in the epithelial and absent in the stromal cells. We demonstrated endometrial GLUT4 expression. The similar results in lean PCOS and control subjects suggest that endometrial GLUT4 expression is not affected by PCOS itself, whereas it is reduced by obesity in PCOS patients.