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Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor β (ERβ), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.

Healthcare providers (HCPs) have an important role in helping women select the contraceptive method that best matches their needs and lifestyle. Recent surveys outline the need of women to be informed about all available choices, including the newest methods (particularly those not requiring daily administration), such as vaginal contraception.The most relevant publications on combined contraceptive vaginal ring are revised in the context of counseling as an opportunity to empower women in term of vaginal health and sexual functioning.HCPs should explain the main characteristics of the combined contraceptive vaginal ring including the anatomical and physiological implications that make the vagina an ideal route of hormonal administration and the basic notions about functional modifications of the vagina during reproductive life. Clinical data on the vaginal ring should be summarized with regard to efficacy, tolerability, pharmacokinetics, cycle control and user acceptability, including recent findings on extra-contraceptive benefits (also compared to other hormonal contraceptives) on the vaginal flora and on sexual function.Vaginal contraception offers various benefits and should always be discussed during contraceptive counseling. An open dialogue about vaginal contraception will also help enhance body knowledge and sexual health.

To test the velocimetric pattern of the ovarian artery as a routine ovarian reserve test.We enrolled 317 consecutive patients from January 2011 to June 2012. At the second day of the menstrual cycle, a transvaginal ultrasound was performed to evaluate the antral follicle count and ovarian volume, and Doppler of both ovarian arteries was also performed. Controlled ovarian stimulation was performed and the patients were divided in two groups according to the result of the intrauterine insemination: group A (nonpregnant women) and group B (pregnant women).Ovarian velocimetric pattern was similar between the two groups. Follicle stimulating hormone value had a significant correlation with the ultrasound markers; however, the multiple regression linear analysis showed that the only independent variables were the antral follicle count (t = -2.74, p = 0.008) and the systolic/diastolic ratio (t = 3.95, p = 0.0005). The best parameters in predicting the pregnancy were the mean ovarian volume, total and partial antral follicle count between 7 and 10 mm, and the mean resistance index (area under the curve: 0.744, 0.671, 0.667, 0.573, respectively).The Doppler study of the ovarian arteries did not add significant information about the ovarian reserve status. Only the mean resistance index had a significant diagnostic accuracy, but its specificity (53%) is too low to consider it a screening test.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery and it remains a diagnostic and therapeutic challenge. The latest Confidential Enquiry into Maternal Deaths (2006-2008) showed that VTE is now the third leading cause of direct maternal mortality, beside sepsis and hypertension. In particular the prevalence of VTE has been estimated to be 1 per 1000-2000 pregnancies. The risk of VTE is five times higher in a pregnant woman than in non-pregnant woman of similar age and postpartum VTE is more common than antepartum VTE. A literature search was carried out on Pubmed using the following key words: "venous thromboembolism", "pregnancy", "risk factors", "prophylaxis", "anticoagulants". Studies from 1999 onwards were analyzed. This review aimed to provide an update of whole current literature on VTE in pregnancy highlighting the most recent findings in diagnostic and therapeutic strategies, considering in detail risks and benefits of various techniques and drug classes, for both mother and fetus. Large trials of anticoagulants administration in pregnancy are lacking and recommendations are mainly based on case series and on expert opinions. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women with current or previous VTE.

Vulvar intraepithelial neoplasia (VIN) is a premalingnant condition. For long time, surgery was considered the first-line therapy in the treatment of high grade VIN. Imiquimod was recently introduced as an alternative to surgery.To compare the overall complete response, the recurrence rate and the risk factors for relapse among patients with VIN 2/3 treated with Imiquimod or surgical excision.Eighty women who had histological diagnosis of VIN 2 and VIN 3 were enrolled in this prospective study. Patients immunocompromised, with recurrent VIN, with well differentiated type VIN or VIN 1 and women treated more than once were excluded from the study. Patients were divided into two groups: group A was treated with Imiquimod, group B underwent surgical excision. Patients' characteristics analyzed were: age, smoking, degree of the primary lesion, state of margins, multifocal disease. We have evaluated the recurrence rate, the relapse rate, and the overall complete response, considering as recurrence the onset of a lesion after an initial complete response to Imiquimod and/or after the surgical treatment and as relapse all patients who had a recurrence plus those with medical treatment failure.Multifocal lesions (p = 0.03) and VIN 3 (p = 0.002) were associated with a higher risk of relapse. The recurrence rate was higher in the group B (p = 0.009), but the relapse rate was higher in the group A (p = 0.04). The overall complete response was better in the group B (p = 0.04).Although the advent of new medical options can decrease the morbidity associated with invasive surgical procedures, surgical treatments remain the best treatment modality for VIN with regard to relapse and overall complete response.

Inadequate cervical sampling is the most frequent cause of misdiagnosis in cervical cancer screening. The aim of this study was to test the ability of PapCone® versus the conventional sampling method (Ayre's spatula plus cytobrush) to collect ectocervical and glandular cells.In 18 healthy women, two ecto-endocervical samples, obtained by two different methods, were obtained at a three-month interval. Qualitative and quantitative parameters were evaluated. Ultrastructure features of sampling devices were analyzed by scanning electron microscopy (SEM) before and after sampling.The χ(2) test revealed a statistically significant difference between the two methods: PapCone® caused less cell overlap and sampled less white blood cells (p0.05) and more metaplastic cells (p0.01). SEM evaluation highlighted the porous and spongy structure of PapCone® that was responsible for the large number of glandular cells on its surface.Cervical smears performed by PapCone® were adequate and generally easier to screen than conventionally performed ones.

Current Controlled Ovarian Stimulation (COH) for Assisted Reproductive Techniques (ART) pursues three main objectives: hypophyseal activity suppression, multiple follicle growth stimulation, and ovulation induction. By suppressing hypophyseal activity, it is possible to prevent untimely LH surge and allow the appropriate development of the leading follicle. The classical GnRH agonist long protocol is the most widely used in COH for ART. However, an alternative regimen based on GnRH antagonist has been recently introduced in clinical practice. As competitive antagonists, these drugs display an immediate and quickly reversible effect and they avoid hormonal withdrawal side effects. Moreover, this protocol shows undeniable advantages, including the shorter duration of the treatment, the lower amount of gonadotropin required, the shorter hormonal and ultrasound monitoring of patients, milder physical and emotional stress, and a lower risk of Ovarian Hyperstimulation Syndrome (OHSS). The use of GnRH antagonists was traditionally restricted to selected patients, as "poor responders" and women at high-risk of developing OHSS such as Polycystic Ovary Syndrome (PCOS) and patients who had previously experienced OHSS. These findings could prompt a trend to change from the standard agonist protocol to the antagonist protocol in all categories of patients. This review provides a comprehensive overview of the use of GnRH antagonist protocols applied both to IVF techniques and to IUI procedures in the Italian experience.

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Microcolposcopy is an in vivo cytological examination of the uterine cervix allowing the localization of exoendocervical precancerous lesions. The aim of this study was to assess the diagnostic reliability of microcolposcopy by means of correlation with histology, colposcopy and Pap test results. For the study, 256 patients with abnormal Pap test results were selected and subjected to colposcopy and microcolposcopy with the aim of evaluating the presence of any intraepithelial lesions. One hundred and nine of these patients were subjected to a biopsy. Colposcopy, histology and cytology results were compared with those obtained by microcolposcopy. In low-grade squamous intraepithelial lesion (LSIL) cytology cases, the percentage agreement on lesion grade between Pap test and microcolposcopy results was 74%, while in high-grade squamous intraepithelial lesion (HSIL) cytology cases, it was equal to 80%. The comparison between colposcopy and microcolposcopy showed a level of agreement of 72% for lower grades and 68% for higher grades. Finally, histology was in agreement with microcolposcopy in 73% of cervical intraepithelial grade 1 neoplasia (CIN 1) cases and reached 71% for CIN 2-3. Microcolposcopy proved to be accurate with regard to the diagnosis of lesion grade, and showed to be definitive in patients where cytology was positive for HPV infection and colposcopy was not able to identify any lesions.

The incidence of cervical cancer in pregnancy is estimated to be 1-10/10000 pregnancies. Approximately 3% of cervical cancers are diagnosed during pregnancy. The incidence of abnormal Pap smears has been reported to be 5%-8%. Data on the spontaneous evolution of an intraepithelial neoplasia during pregnancy are quite diverse. Of dysplasia cases diagnosed during pregnancy, 10%-70% regress and sometimes even disappear postpartum, while persistence in the severity of cervical neoplasia is reported in 25%-47% and progression occurs in 3%-30%. However, adequate follow-up and definitive management in the postpartum period is important. The objective of the study was to assess proper management of squamous intraepithelial lesion (SIL) during and after pregnancy, to assess regression, persistence and risk of progression and the predictive role of HPV tests.Thirty-one out of 721 pregnant women with a diagnosis of low- and high-grade SIL were observed. All patients were triaged using standard colposcopy. The histological diagnosis was assessed by colposcopic direct biopsies. In patients affected by high-SIL with colposcopic findings of suspected micro-invasive lesions, a loop electrosurgical excisional procedure (LEEP) was carried out in pregnancy. High risk HPV tests were performed using PCR. The patients were followed up with cytology and colposcopy every 6-8 weeks during gestation and nine weeks postpartum. They were re-evaluated using cytology, colposcopy and histology for a final diagnosis and, when necessary, submitted to treatment. The patients were followed up for a minimum of 5 years. The HPV test was performed once at 6-8 weeks during gestation and annually during the follow-up.Of the 31 patients with abnormal cytology, histological analysis revealed 10 cervical intraepithelial neoplasia (CIN) 1, 5 CIN 2 and 16 CIN 3. The HPV test at diagnosis was positive for HPV 16 type in 22 cases and negative in 9. Five patients with CIN 2 and 11 with CIN 3 were followed up; 5 patients with CIN 3 with colposcopic findings of suspected microinvasive lesions were submitted to an excisional procedure with LEEP before the 16th week of pregnancy.Performing high-risk HPV tests may improve the follow-up of patients with SIL in pregnancy and postpartum in addition to cytology and colposcopy to indicate persistence/progression of the lesions. Proper management and adequate follow-up could be proposed in pregnancy and postpartum.

To evaluate the existence of an association between cervicovaginal infections and precancerous lesions of the uterine cervix, through determination of prevalent cervicovaginal micro-organisms, alone and in association with human papillomavirus (HPV), in patients with abnormal and normal vaginal cytology.Patients with abnormal vaginal cytology were divided into three study groups according to cytological findings: ASC-US, L-SIL and H-SIL. All patients underwent colposcopic examination and exoendocervical and vaginal sampling for microbiological and molecular analysis for detection of HPV-DNA, Ureaplasma urealyticum, Chlamydia trachomatis, Trichomonas vaginalis, mycetes and common bacteria. Results were compared with the patient group asymptomatic for cervicovaginal inflammation with negative vaginal cytology and colposcopy.A high association between Ureaplasma urealyticum infection and the grade of cytological cervical lesion (27% for ASC-US, 35% for L-SIL and 45% for H-SIL) was found. Furthermore, 19% of the control group samplings were positive for Ureaplasma urealyticum, significantly less than that observed in the positive cytology groups. An interesting association of HPV with Ureaplasma urealyticum in patients with H-SIL vaginal cytology (83%), much higher than that observed in patients with slightly abnormal or normal vaginal cytology (56% for ASC-US, 49% for L-SIL, 40% for normal cytology) was also identified. In contrast, the association between Papillomavirus and multiple microorganisms seemed to decrease with the level of cellular dysplasia in 30% of controls, 33% of ASC-US, 32% of L-SIL and 17% of H-SIL.The presence of a high Ureaplasma urealyticum level seems to be a cofactor of HPV infection, a necessary cause of precancerous lesions of the uterine cervix. The presence of Ureaplasma urealyticum may play a role both in initiating viral cellular anomalies and in viral persistence. It can be hypothesized that these initial processes are helped by a state of cervical inflammation, also supported by multiple microorganisms. It would, thus, be suggested for all patients who present with an abnormal PAP test to undergo a cervicovaginal microbiological examination to detect potentially pathogenic microbes for correct diagnosis and treatment, as well as a more complete follow-up of cervical cytological lesions.

The objective of the study was to evaluate the effects of laser CO2 surgery during pregnancy to prevent clinical HPV infection recurrence after delivery and vertical infection. A case-control study was performed on 280 pregnant women affected by clinical HPV infection treated during pregnancy with 256 women treated three months after delivery. Follow-up was performed for a minimum of three colposcopic examinations for two years. Recurrence rates were calculated considering the number of positive findings for at least one colposcopic examination confirmed by biopsy after a negative control in a year. Statistical comparison of rates was performed by chi-squared and Fisher's exact test. Recurrence rates were higher in the women treated in postpartum (p.01) than in the group treated during gestation (p.005). Clinical HPV infections treated during the second trimester of pregnancy showed a sensitive decrease in recurrence-rate of infection. Rarity of respiratory papillomatosis makes conclusions inconsistent for the prevention of vertical infection.