Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features.

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 ß (ERß), 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, ERß, 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.

The ultrasonographic detection of follicular rupture at the time of intrauterine insemination: is it really decisive?

Our aim is to assess the impact of the ultrasonographic detection of follicular rupture on the intrauterine insemination success. A total of 313 women undergoing ovarian stimulation for intrauterine insemination were enrolled. Transvaginal ultrasonography was performed to check whether the dominant follicle had ruptured and according to that the patients were divided into two groups. The ultrasound detection of follicular rupture was observed in 156 patients (54%). The independent variables favoring follicular rupture were: Age (t: 7.646, p < 0.0005), FSH value (t: -5.637, p < 0.0005), duration of infertility (t: -4.265, p < 0.0005), menstrual cycle length (t: -4.927, p < 0.0005). Moreover, the logistic regression analysis demonstrated that the predictive variables for follicular rupture were: FSH value (OR 1.7, CI 95% 1.3-2.3, p < 0.0005), duration of infertility (OR 2.6, CI 95% 1.6-4.2, p < 0.0005) and menstrual cycle length (OR 2.4, CI 95% 1.7-3.4, p < 0.0005). Pregnancy occurred in 23 patients of the group A (14.7%) and in 22 patients of the group B (16.5%) without a significant difference (p = 0.6). The logistic regression analysis confirmed that neither the evidence of follicular rupture nor any other variables influenced the pregnancy rate.

The role of ovarian fossa evaluation in patients with ovarian endometriosis.

PURPOSE: The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma. METHODS: Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out. RESULTS: 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p < 0.0001). Pain symptoms were more frequent in patients with endometriomas adhesion to the ovarian fossa. CA125 levels were not statistically significantly different between groups. At 12-month follow-up, four patients presented endometrioma recurrence. All of them presented adhesion of the ovarian fossa to the endometrioma in the first operation. CONCLUSIONS: There is a strong association between adhesion of the endometriomas to the ovarian fossa and the presence of endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

Clinical factors and malignancy in endometrial polyps. Analysis of 1027 cases.

STUDY OBJECTIVE: To assess the prevalence of polyps carrying a malignancy and match association between clinical factors and oncologic progression. STUDY DESIGN: A retrospective study (Canadian Task Force classification II-3) at a university hospital in Rome, Italy. We retrospectively analyzed data from 1027 women consecutively treated for endometrial polyps at our center in the period 2002-2011. The association of malignancy with hormonal status, tamoxifen, hypertension, symptoms, diabetes mellitus, obesity, and hormonal replacement therapy in pre- and post-menopausal women was assessed. RESULTS: Mean age was 45.8±10.8 years. Benign polyps accounted for 95.8% of the total, pre-malignant for 2.67%, malignant for 1.54%. Our data showed that post-menopausal and older women (>60y) with endometrial polyps have a higher risk of developing a related endometrial cancer (OR: 3.05, 95% CI [1.54, 6.19], p<0.001 and OR: 2.8, 95% CI [1.38, 5.56], p≤0.003. Also we observed that women with AUB in the post-menopausal period displayed a risk of malignancy (OR: 31.1, 95% CI [10.3,111], p value <0.001). CONCLUSION: Special attention should be drawn to symptomatic post-menopausal patients that appear to be at higher risk of malignancy. Symptomatic pre-menopausal women and asymptomatic post-menopausal women with polyps may be a group with intermediate-risk. These patients should undergo an individualized management plan, balancing both risks and benefits of surgical intervention after discussion with the patient.

Exposure to endocrine disrupters and nuclear receptor gene expression in infertile and fertile women from different Italian areas.

Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.

Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study.

Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors - Galectin-3 and Stimulation Expressed Gene 2 - in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis.

Doppler velocimetry of the ovarian artery as a tool to detect LH surge in stimulated cycles.

Our aim was to assess the velocimetric pattern of the ovarian artery as a possible marker of LH surge in stimulated cycles. A total of 130 women undergoing ovarian stimulation for intrauterine insemination were randomized in two groups. Each woman was stimulated with 75 IU of recombinant FSH starting from the third day of the cycle. Velocimetric indices of the dominant ovarian artery were compared between patients with spontaneous LH surge and those needing HCG administration to trigger dominant follicle rupture. The pulsatility index and the ratio between peak systolic flow and lowest diastolic flow were significantly higher in women that had a spontaneous triggering of ovulation. These parameters had a high and very significant positive correlation with the dosage of luteinizing hormone. Threshold values of 2.60 for PI and 7.68 for S/D had a high sensitivity and specificity to predict LH surge. These velocimetric results demonstrated that an increased resistance in the dominant ovarian artery is correlated to LH surge in stimulated cycles. It may represent a sign of relevant clinical utility in timing of intrauterine insemination and/or natural intercourse.

Bisphenol A and the female reproductive tract: an overview of recent laboratory evidence and epidemiological studies.

Bisphenol A (BPA) is a high production volume monomer used for making a wide variety of polycarbonate plastics and resins. A large body of evidence links BPA to endocrine disruption in laboratory animals, and a growing number of epidemiological studies support a link with health disorders in humans. The aim of this review is to summarize the recent experimental studies describing the effects and mechanisms of BPA on the female genital tract and to compare them to the current knowledge regarding the impact of BPA impact on female reproductive health. In particular, BPA has been correlated with alterations in hypothalamic-pituitary hormonal production, reduced oocyte quality due to perinatal and adulthood exposure, defective uterine receptivity and the pathogenesis of polycystic ovary syndrome. Researchers have reported conflicting results regarding the effect of BPA on premature puberty and endometriosis development. Experimental studies suggest that BPA's mechanism of action is related to life stage and that its effect on the female reproductive system may involve agonism with estrogen nuclear receptors as well as other mechanisms (steroid biosynthesis inhibition). Notwithstanding uncertainties and knowledge gaps, the available evidence should be seen as a sufficient grounds to take precautionary actions against excess exposure to BPA.

Pregnancy in a unicornuate uterus: a case report.

INTRODUCTION: A unicornuate uterus accounts for 2.4 to 13% of all Müllerian anomalies. A unicornuate uterus with a non-communicating rudimentary horn may be associated with gynecological and obstetric complications such as infertility, endometriosis, hematometra, urinary tract anomalies, abortions, and preterm deliveries. It has a poor reproductive outcome and pregnancy management is still unclear. CASE PRESENTATION: We report a case of a 26-year-old Caucasian woman presenting with a unicornuate uterus with a non-communicating rudimentary horn. The diagnosis of the anomaly was based on two-dimensional and three-dimensional sonography. The excision of her symptomatic rudimentary horn and her ipsilateral fallopian tube was performed laparoscopically. The growth of the fetus was normal. At 20 weeks' pregnancy, her cervix started shortening and a tocolytic therapy was started. A cesarean delivery was successfully performed at 39 weeks and 4 days' gestation. CONCLUSIONS: Although the reproductive outcome of women with unicornuate uterus is poor, a successful pregnancy is possible. Routine excision of the rudimentary horn should be undertaken during non-pregnant state laparoscopically, and it would be necessary to screen such pregnancies for the development of intrauterine growth retardation with serial ultrasound assessments of the estimated fetal weight and the cervix length.

The risk factors for failure of labor induction: a cohort study.

PURPOSE: To assess how some factors may influence the failure of labor induction. METHODS: We conducted a prospective observational study from January 2009 to December 2011 with 248 patients who were admitted to the Obstetrics Unit of Ferrara University for labor induction. We selected only patients with unfavorable characteristics such as nulliparity, maternal and gestational age, and Bishop score and specific obstetric conditions such as mild preeclampsia, isolated oligohydramnios, premature rupture membrane, gestational diabetes, and hypertension for the success of labor induction. RESULTS: The induction was carried out by rapid-release gel dinoprostone. 200 patients (80.6 %) delivered vaginally (Group A), while 48 (19.4 %) underwent a cesarean section (Group B). Maternal age was one independent significant variable (p = 0.01, OR 1.08) determining the risk of cesarean delivery. Patients affected by mild preeclampsia had a three times higher risk for cesarean section. Despite the several unfavorable characteristics of the patients, the cesarean section rate was comparable to that of the normal population. CONCLUSIONS: Several factors and clinical conditions historically considered as negative predictors of induction result should be reassessed. The success of labor induction is determined by many maternal and fetal variables, which must all be taken into account to avoid unnecessary cesarean sections.

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

BACKGROUND: The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. OBJECTIVE: The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. STUDY DESIGN: Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. RESULTS: The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. CONCLUSION: HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up.

Can Doppler study of the ovarian artery predict the fertility outcome of intrauterine insemination?

BACKGROUND: To test the velocimetric pattern of the ovarian artery as a routine ovarian reserve test. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping.

Metabolic syndrome is an increasing pathology in adults and in children, due to a parallel rise of obesity. Sedentary lifestyle, food habits, cultural influences and also a genetic predisposition can cause dyslipidemia, hypertension, abdominal obesity and insulin resistance which are the two main features of metabolic syndrome. Polycystic ovary syndrome (PCOS) is a condition directly associated with obesity, insulin resistance (HOMA index) and metabolic syndrome, and it is very interesting for its relationship and overlap with the metabolic syndrome. The relationship between the two syndromes is mutual: PCOS women have a higher prevalence of metabolic syndrome and also women with metabolic syndrome commonly present the reproductive/endocrine trait of PCOS. Prevention and treatment of metabolic syndrome and PCOS are similar for various aspects. It is necessary to treat excess adiposity and insulin resistance, with the overall goals of preventing cardiovascular disease and type 2 diabetes and improving reproductive failure in young women with PCOS. First of all, lifestyle changes, then pharmacological therapy, bariatric surgery and laparoscopic ovarian surgery represent the pillars for PCOS treatment.

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate.

PURPOSE: To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery. METHODS: The inclusion criteria of this study were: (1) 25-40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma. RESULTS: In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01). CONCLUSIONS: Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.

Multiple intraepithelial neoplasias of the lower female genital tract: the reliability of HPV mRNA test.

OBJECTIVE: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms. MATERIALS AND METHODS: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment. RESULTS: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02). CONCLUSIONS: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

Evaluation of serum anti-Mullerian hormone levels to assess the ovarian reserve in women with severe endometriosis.

OBJECTIVE: The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with severe endometriosis, in order to demonstrate the effect of the disease on ovarian reserve. STUDY DESIGN: Prospective case-control study. One hundred and ninety-five patients were enrolled: 130 fertile patients (group A) and 65 patients with stage III and IV endometriosis, diagnosed by laparoscopy and histological examination (group B). AMH serum levels were measured in both groups and were compared using Student's t-test. RESULTS: The two groups were homogenous for main demographic data. Group B had statistically significantly lower mean AMH serum levels (0.97±0.59ng/ml) than group A (1.72±0.63ng/ml) (p=0.001). CONCLUSIONS: This study is a demonstration of the damage of endometriosis on ovarian reserve, leading to a form of incipient ovarian failure, which is considered as an early sign of advanced ovarian depletion in young women. These findings suggest that AMH could be used in the follow-up of patients with endometriosis, in order to assess promptly the decrease of ovarian reserve.

Correlation of endocrine disrupting chemicals serum levels and white blood cells gene expression of nuclear receptors in a population of infertile women.

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ER α , ER ß , AR, AhR, PXR, and PPAR γ ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ER α , ER ß , AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ER α , ER ß , AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects.

Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia.

OBJECTIVE: To determine pregnancy outcomes among women who underwent loop electrosurgical excision procedure (LEEP). METHODS: In a case-control study in Italy, 475 pregnant women who underwent LEEP and 441 untreated pregnant women were enrolled between January 2003 and January 2007. Outcome measures were spontaneous abortion, preterm delivery, and at-term delivery rates. Continuous and discrete variables were analyzed via t, χ(2), and Fisher exact tests. Groups were compared by analysis of variance and Tukey HSD test. RESULTS: The spontaneous abortion rate was 14.5% and 14.1% in the LEEP and untreated groups, respectively. The preterm delivery rate was 6.4% and 5.0% in the LEEP and untreated groups, respectively. The number of women with a cervical length of less than 30mm was higher in the LEEP group, but this did not influence preterm delivery rate (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.53-1.95). Among women with a cervical length of less than 15mm, those treated with a wider removal of cervical tissue showed increased risk of preterm delivery (OR, 5.31; 95% CI, 1.01-28.07). CONCLUSION: The preterm delivery rate was not higher among women who underwent LEEP than among untreated women. Preterm delivery was associated with cone size and cervical length in the second trimester.

Pain in the upper anterior-lateral part of the thigh in women affected by endometriosis: study of sensitive neuropathy.

OBJECTIVE: To assess whether pain in the anterior-lateral part of the thigh in women affected by endometriosis is due to femoral nerve invasion by endometriotic implants. DESIGN: Case-control study. SETTING: Hospital. PATIENT(S): We enrolled 30 patients with endometriosis and leg pain in the anterior-lateral part of the thigh and 30 healthy women. INTERVENTION(S): Skin biopsy and neurologic examination for detection of neuropathy. MAIN OUTCOME MEASURE(S): Intraepidermal small fiber density reduction and positive neurologic examination agree with sensitive neuropathy. RESULT(S): Biopsy results showed no statistically significant difference between the case group and the control group. At neurologic examination nine patients in the study group (30%) showed positive results, none in the control group showed signs. These nine patients had reduced intraepidermal small fiber density, compared to the lower cutoff values of the control group, suggesting a sensitive neuropathy. CONCLUSION(S): When there is leg pain in women with endometriosis it is important to distinguish neuropathic from referred pain. Skin biopsy and neurologic examination should be introduced in the management of leg pain in endometriosis, due to their low invasiveness to diagnose a sensitive neuropathy. As a result early detection of nerve injury and planning for a prompt specific treatment would be possible.

Satisfactory sampling in cytological cervical diagnosis: comparison between a conventional and a new sampling device.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: The χ(2) test revealed a statistically significant difference between the two methods: PapCone® caused less cell overlap and sampled less white blood cells (p<0.05) and more metaplastic cells (p<0.01). SEM evaluation highlighted the porous and spongy structure of PapCone® that was responsible for the large number of glandular cells on its surface. CONCLUSION: Cervical smears performed by PapCone® were adequate and generally easier to screen than conventionally performed ones.