Diego Marchesoni

Frequency of Factor V, Prothrombin and Methylenetetrahydrofolate Reductase Gene Variants in Preeclampsia

Background: The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was investigated in a north-eastern Italian population. Methods: Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated. Genotypes were determined by polymerase chain reaction. Results: The frequency of heterozygous carriers of the factor V Leiden was similar between PE women (5.2%) compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A and C677T mutations were similar between PE and control subjects. Conclusions: In this population, we found no difference in the prevalence of genetic risk factors for thrombosis in women with preeclampsia compared with control subjects.

Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia.

It is known that the plasminogen activator inhibitor 1 (PAI-1) protein levels are increased in placentas of preeclamptic subjects. Therefore, we assessed whether polymorphisms related to the transcriptional control of the PAI-1 gene (–675 4G/5G and –844G/A) are associated with mild preeclampsia. We compared 52 women with preeclampsia to 80 women with a normal pregnancy. None of the preeclamptic women suffered from the severe form of preeclampsia. DNA was extracted from blood, and –675 4G/5G and –844G/A genotypes of the PAI-1 gene were determined. Since it has been shown that the presence of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene variants may be associated with preeclampsia, their frequency was also evaluated in our study groups. The factor V Leiden, PT G20210A, and MTHFR C677T gene variants were not associated with preeclampsia. In the case of the –675 4G/5G polymorphism, genotypes 4G/4G and 5G/5G were more prevalent in the preeclamptic and in the control group, respectively. In the case of –844 G/A polymorphism, genotypes A/A and G/G were more prevalent in the preeclamptic and in the control group, respectively. By using the χ2 test for trend, differences for both genotypes were significant (p = 0.0141 for the –675 genotypes and p = 0.0492 for the –844 genotypes). The frequency of the 4G and 5G alleles of the –675 gene polymorphism was significantly different between preeclamptic and normal women (p = 0.032). Differently, the allelic frequency of the –844 gene polymorphism did not show significant differences between preeclamptic and normal women (p = 0.083). In conclusion, the hypofibrinolytic genotypes 4G/4G and A/A at positions –675 and –844 of the PAI-1 gene are associated with the occurrence of mild preeclampsia independently of thrombophilic mutations of the factor V, prothrombin, and MTHFR genes.

Obesity Reduces the Expression of GLUT4 in the Endometrium of Normoinsulinemic Women Affected by the Polycystic Ovary Syndrome

Abstract: 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.

Morbus Paget der Vulva: Remission durch Lokalbehandlung mit Imiquimod – Fallbericht und Literaturübersicht

Der Morbus Paget ist eine seltene Erkrankung der Vulva, welche weniger als 1% aller Neoplasien der Vulva ausmacht. Die übliche Therapie besteht in der lokalen chirurgischen Entfernung. Während die invasive Form des Morbus Paget selten ist, stellen die häufigen Lokalzrezidive, welche nicht mehr chirurgisch behandelt werden können, ein bedeutendes klinisches Problem dar. Bei einer 71-jährigen Patientin wurde ein solches Rezidiv erfolgreich mit Imiquimodsalbe behandelt. Die Juckreizsymptome bildeten sich nach kurzer Zeit zurück. Nach 4 Wochen waren die kolposkopisch sichtbaren Hauterscheinungen rückläufig. Innerhalb von 8 Wochen kam es zu einer kompletten klinischen Remission. Die Lokalbehandlung mit Imiquimod ist demnach nicht nur bei der vulvären intraepithelialen Neoplasie erfolgversprechend, sondern stellt auch bei ausgewählten Patientinnen mit rezidivierendem Morbus Paget der Vulva eine konservative Behandlungsalternative dar.

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.

A proposal for a new scoring system to evaluate pelvic masses: Pelvic Masses Score (PMS)

OBJECTIVES Ovarian cancer is the fourth leading cause of death among neoplastic diseases in women. In spite of constant improvement in surgical, chemotherapeutic and immunologic techniques, which can induce long remission periods, the five-year survival rate has not really changed over the past thirty years. We tried to create a sonographic scoring system, called PMS, that could be helpful in diagnosis of pelvic masses. STUDY DESIGN The three most commonly used and validated indexes--Sassone score, Ovarian Tumor Index (OTI), and Risk of Malignancy Index 3 (RMI3)--were applied to a population of 102 women with adnexal masses. We developed a new scoring system, named Pelvic Masses Score (PMS), that takes into account the ultrasound morphological pattern, the Doppler flowmetry of the pelvic mass, the CA125 serum level and the menopausal status. We then applied this scoring system to a population of 160 women for validation of the score. RESULTS Statistical analysis of the data obtained from the new scoring system reveals that sensitivity, specificity, positive and negative predictive values (PPV and NPV) are higher than in the case of data separately derived from the Sassone score, OTI index or RMI index. CONCLUSIONS Our preliminary data showed good results in term of sensitivity, specify and predictive values compared to other old scoring systems. A larger prospective study is required to confirm these preliminary data. The number of cases will be expanded to permit a better evaluation of PMS.

New and old predictive factors for breech presentation: our experience in 14 433 singleton pregnancies and a literature review

Abstract Objective: Breech presentation represents a common indication for primary cesarean section in women presenting for parturition. This study aims to investigate the presence of new and old risk factors for breech presentation and to provide a literature review. Method: In this population-based retrospective cohort study, we collected data from 14 433 consecutive singleton deliveries occurred in a 3rd level hospital setting of northeast Italy between January 2001 and July 2009. Related risk factors and trends in breech presentation prevalence were also considered. Results: Mean maternal age was 31.78 years (±5.17) and mean gestational age at delivery 38.67 weeks (±2.54). Breech presentation prevalence in nullipara and pluripara was respectively 5.36% (415/7743) and 3.53% (236/6689; p < 0.05), and was significantly lower among Sub-Saharan-African women 2.62% (14/535) versus 4.51% (651/14432; p < 0.05). Also advanced maternal age, early gestational age at delivery, neonatal female gender and low weight at delivery resulted associated with a higher prevalence of breech presentation. By multivariate logistic regression, the breech presentation resulted independently predicted by maternal age, ethnicity, parity, gestational age and neonatal weight MoMs at delivery, and neonatal gender. Conclusions: Advanced maternal age, early gestational age, low neonatal weight MoMs at delivery and female gender resulted to be risk factors for fetal breech presentation at delivery, while multiparity and Sub-Saharan-African ethnicity resulted to be protective.

Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia

The aim of this study was to evaluate the correlation between genetic thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and preeclampsia.

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

Abstract 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.

Endometrial histologic changes in post-menopausal breast cancer patients using tamoxifen

Objective: The aim of this study was to evaluate the effect of tamoxifen on the endometrium of post‐menopausal women with breast cancer and to examine the relationship between ultrasonography, hysteroscopy and histopathologic changes. Method: Included in this longitudinal study were 303 post‐menopausal women taking 20 mg daily of tamoxifen. Hysteroscopy was performed in 83 patients with an endometrial thickness of only ≥5 mm and 34 with vaginal bleeding also. Forty‐five asymptomatic patients (control group) underwent hysteroscopies. Result: The most frequent outcome in patients with endometrial thickness of only ≥5 mm was an atrophic endometrium in an empty cavity (79.5%) whereas simple hyperplasia (35.3%) was found in women with vaginal bleeding. Carcinoma was diagnosed in seven cases (5.9%). In the control group, no endometrial cancer was found. Conclusion: This study suggests that patients with a thickness >5 mm should be offered a whole hysteroscopic evaluation, whenever bleeding is reported.