Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects.

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.

A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.

BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).

Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors.

PURPOSE: The aim of this study was to evaluate the efficacy of fractional CO2 laser therapy in breast cancer survivors as a therapeutic method for vulvovaginal atrophy (VVA) dyspareunia. METHODS: 50 patients (mean age 53.3 years) underwent fractional microablative CO2 laser treatment for dyspareunia in oncological menopause (mean time of menopause 6.6 years). The Gloria Bachmann's Vaginal Health Index (VHI) score was chosen as system to evaluate the presence of VVA and its improvement after the treatment. Intensity of dyspareunia was evaluated using a visual analog scale (VAS). RESULTS: Data indicated a significant improvement in VVA dyspareunia (p < 1.86e-22) in breast cancer survivors who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were significantly higher 30 days post-treatment (T4) (p < 0.0001). 76 % of patients were satisfied or very satisfied with the treatment results. The majority (52 %) of patients were satisfied after a long-term follow-up (mean time 11 months). No adverse events due to fractional CO2 laser treatment occurred. CONCLUSIONS: The treatment with fractionated CO2 laser appeared to be a feasible and effective treatment for VVA dyspareunia in breast cancer survivors with contraindications to hormonal treatments.

Management options of breast cancer related osteoporosis.

Breast cancer therapy after surgery has been improved in recent years. Adjuvant therapies like aromatase inhibitors are being extensively used among breast cancer survivors. This leaded to cancer related and iatrogenic osteoporosis. Management of these patients needs to be focused and differentiated from the standard age related osteoporosis in women. All guidelines consider mandatory to assess fracture risk periodically in all breast cancer survivors. Risk assessment diagnostic FRAX tool is the most used but it's not born specifically for cancer related osteoporosis. The therapeutic management of this kind of osteoporosis has been studied by different societies. Since breast cancer survivors are at risk of osteopenia and osteoporosis, counseling regarding modifiable risk factors is mandatory and advocated. The beginning of the treatment should be tailored in each patient.

Efficacy of rifaximin vaginal tablets in treatment of bacterial vaginosis: a molecular characterization of the vaginal microbiota.

Bacterial vaginosis (BV) is a common vaginal disorder characterized by an alteration of the vaginal bacterial morphotypes, associated with sexually transmitted infections and adverse pregnancy outcomes. The purpose of the present study was to evaluate the impact of different doses of rifaximin vaginal tablets (100 mg/day for 5 days, 25 mg/day for 5 days, and 100 mg/day for 2 days) on the vaginal microbiota of 102 European patients with BV enrolled in a multicenter, double-blind, randomized, placebo-controlled study. An integrated molecular approach based on quantitative PCR (qPCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to investigate the effects of vaginal tablets containing the antibiotic. An increase in members of the genus Lactobacillus and a decrease in the BV-related bacterial groups after the antibiotic treatment were demonstrated by qPCR. PCR-DGGE profiles confirmed the capability of rifaximin to modulate the composition of the vaginal microbial communities and to reduce their complexity. This molecular analysis supported the clinical observation that rifaximin at 25 mg/day for 5 days represents an effective treatment to be used in future pivotal studies for the treatment of BV.

The effects of uterine fundal pressure (Kristeller maneuver) on pelvic floor function after vaginal delivery.

PURPOSE: To evaluate the role of uterine fundal pressure during the second stage of labor (Kristeller maneuver) on pelvic floor dysfunction (urinary and anal incontinence, genital prolapse, pelvic floor strength). METHODS: 522 primiparous women, enrolled 3 months after vaginal delivery, were divided in two groups: group A (297 women) identifies the women who received Kristeller maneuvers with different indications (e.g. fetal distress, failure to progress, mother exhaustion), group B (225 women) the women without maneuver. Participants were questioned about urogynecological symptoms and examined by Q-tip test, digital test, vaginal perineometry and uroflowmetric stop test score. RESULTS: Mediolateral episiotomies, dyspareunia and perineal pain were significantly higher in Kristeller group, whereas urinary and anal incontinence, genital prolapse and pelvic floor strength were not significantly different between the groups. CONCLUSIONS: Kristeller maneuver does not modify puerperal pelvic floor function but increases the rate of episiotomies.

Tubercular endometritis visualized as endometrial micropolyps during hysteroscopic procedure.

Female genital tuberculosis is a rare disease in developed countries but it is a frequent cause of chronic pelvic inflammatory disease and infertility in undeveloped countries. A rare case of tubercular endometritis diagnosed at hysteroscopy and successfully treated in a woman with secondary infertility, is presented. As far as we know this is the first case that shows the association between endometrial micropolyps and tubercular endometritis.

Leukocytospermia and sperm preparation--a flow cytometric study.

BACKGROUND: Leukocytes represent the predominant source of reactive oxygen species both in seminal plasma and in sperm suspensions and have been demonstrated to negatively influence sperm function and fertilization rate in assisted reproduction procedures. Peroxidase test is the standard method recommended by WHO to detect semen leukocytes but it may be inaccurate. The aims of this study were (i) to compare the efficiency of swim-up and density-gradient centrifugation techniques in removing seminal leukocytes, (ii) to examine the effect of leukocytes on sperm preparation, and (iii) to compare flow cytometry and peroxidase test in determining leukocyte concentration in semen using a multiparameter flow cytometric method. METHODS: Semen samples from 126 male partners of couples undergoing infertility investigations were analyzed for leukocytospermia using standard optical microscopy and flow cytometry. Sixty-nine out of 126 samples were also processed using simultaneously the swim-up and density-gradient centrifugation techniques. A multiparameter flow cytometric analysis to assess simultaneously sperm concentration, sperm viability, sperm apoptosis, and leukocyte concentration was carried out on neat and prepared sperm. RESULTS: Both sperm preparation methods removed most seminal leukocytes. However, the concentration of leukocytes was significantly lower after swim-up compared to that after density-gradient centrifugation preparation. Leukocytes concentration, either initial or in prepared fractions, was not correlated with sperm parameters (optical microscopy and flow cytometry parameters) after semen processing. There was no correlation between leukocyte concentration in the ejaculate and sperm recovery rate, whereas a significant correlation was found between the concentration of the residual leukocytes in prepared fractions and viable sperm recovery rate. Although the overall concordance between the flow cytometry and the optical microscopy was satisfactory, the sensitivity of peroxidase test for the detection of leukocytospermia resulted low. CONCLUSION: Seminal leukocytes do not seem to influence sperm preparation results. However, for assisted conception, semen samples containing leukocytes should be processed using swim-up method. Although peroxidase-test is recommended by WHO as the standard method for determining semen leukocytes, it should not be used in clinical research study.

Ascites in puerperium: a rare case of atypical pseudo-Meigs' syndrome complicating the puerperium.

PURPOSE: We report the case of puerperal ascites, associated with elevated CA125 levels and secondary to a uterine myoma. The literature on pseudo-Meigs' syndrome associated with pregnancy was reviewed. CASE: A 35-year-old woman complained of abdominal distension 2 days after a spontaneous vaginal delivery. A mass of 5 cm in the right uterine corner had been detected during the first trimester ultrasound and had been diagnosed as subserosal myoma. Physical examination and ultrasound revealed massive ascites. Computed tomography confirmed ascites and laboratory investigations showed CA125 raised levels. Cytology of ascitic fluid resulted negative for malignancy. A laparotomy was performed and a large pedunculated myoma was removed. A final diagnosis of atypical pseudo-Meigs' syndrome was performed, being computed tomography and chest X-ray negative for pleural effusion. CONCLUSIONS: To the best of our knowledge, this is the first case of pseudo-Meigs' syndrome caused by a uterine leiomyoma described in puerperium and without hydrothorax. Though ascites is very rare in obstetrics, it should be considered when evaluating puerperal patients complaining of abdominal distension.

Effects of third-generation oral contraceptives on high-sensitivity C-reactive protein and homocysteine in young women.

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women. METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m(2)). Seventy-seven oral contraceptive users were compared with 200 non-oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined. RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non-oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99-8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non-oral contraceptive users (odds ratio 3.89; 95% CI 2.03-7.46). Notably, non-oral contraceptive users were 8.65 (95% CI 4.39-17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels. CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.

Resectoscopic treatment of atypical endometrial polyps in fertile women.

OBJECTIVE: The purpose of this study was to evaluate the long-term efficacy and prognosis of hysteroscopic resection and coagulation of the base of endometrial polyps with focal atypia in fertile women with or without progestin suppression. STUDY DESIGN: We conducted a quasi-randomized trial in which conservative treatment was offered to 21 patients who had endometrial polyps with focal atypia and a surrounding normal endometrium. The polyps were analyzed separately from their bases. Random biopsy specimens were taken from 4 standard places of the endometrium. RESULTS: Eighteen women (10 women with an intrauterine device and 8 women with no intrauterine device) completed the follow-up procedure. After 5 years, we found no difference in the 2 groups regarding recurrence of atypical polyps. CONCLUSION: Conservative resectoscopic treatment may be considered in fertile women with atypical polyps if polyp base and surrounding endometrium are benign. If women want to become pregnant at short term, the use of progestins can be delayed, with a strict follow-up procedure. Larger studies should be encouraged.

2017 European guideline for the management of pelvic inflammatory disease.

The European guideline for the management of pelvic inflammatory disease includes evidence-based advice on the investigation and treatment of pelvic inflammatory disease (PID). It has been updated to acknowledge the role of Mycoplasma genitalium as an important cause of PID with testing now recommended for women presenting with possible PID and for the male partners of women with confirmed M. genitalium infection. Recent evidence suggests that serious adverse events are uncommon when using moxifloxacin and its use is now recommended as a first-line therapy, especially in those women with M. genitalium PID. The potential utility of MRI scanning of the pelvis in excluding differential diagnoses has been highlighted. The use of doxycycline is now suggested as empirical treatment for male partners of women with PID to reduce exposure to macrolide antibiotics, which has been associated with increased resistance in M. genitalium.

Menopause and hormone replacement therapy: the 2017 Recommendations of the Italian Menopause Society.

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

The role of mannose-binding lectin gene polymorphisms in women with recurrent bacterial vaginosis.

OBJECTIVE: The objective of the study was to examine mannose-binding lectin gene (MBL2) polymorphisms in women with recurrent episodes of bacterial vaginosis (BV). STUDY DESIGN: Seventy-one women with at least 4 episodes of BV in the last 12 months and 130 healthy controls were enrolled to evaluate all 3 variant alleles of the MBL2 gene (polymorphisms at positions 52, 54, and 57 in the first exon of the MBL2 gene). RESULTS: No statistically significant differences in MBL2 polymorphism allelic and genotype frequencies were observed between women with recurrent BV and controls. Allele A (wild type) was present, respectively, in 78% of patients with recurrent BV and 77% of controls, whereas the allele 0 was present in 22% of women with recurrent BV and 23% of controls. MBL2 genotype and allelic frequencies were similar in the 2 groups, and the 2 populations were in accordance with the Hardy-Weiberg equilibrium. CONCLUSION: Our results indicate that MBL2 gene polymorphisms do not seem to be involved in susceptibility to recurrences of BV in gynecological patients.

Is resectoscopic treatment of atypical endometrial polyps a safe option?

OBJECTIVE: This study was undertaken to evaluate the long-term efficacy and prognosis of hysteroscopic resection and coagulation of the polyp base of endometrial polyps with focal atypia in postmenopausal women. STUDY DESIGN: In this observational noncomparative study, conservative treatment was offered to 16 patients, with high anesthesiologic risk, who had endometrial polyps with focal atypia and a surrounding atrophic endometrium. To confirm the focality of the lesion, the polyps were analyzed separately from their bases. Patients with atypia in the polyp base were excluded. RESULTS: After 5 years of follow-up, 13 patients are disease free, 2 underwent vaginal hysterectomy and annessiectomy due to other causes, and 1 died for cardiac disorders. CONCLUSION: Adenomatous polyps with atypia can be treated resectoscopically if the treatment is associated with an accurate histologic examination of the polyp base and its eventual involvement and the features of the remaining uterine mucosa. A thorough follow-up is recommended. Studies on wider casuistries of patients are needed.

Efficacy, tolerability and safety of a new medical device, Monurelle Biogel(®) vaginal gel, in the treatment of vaginal dryness: a randomized clinical trial in women of reproductive age.

OBJECTIVE: To prove the efficacy, tolerability and safety of Monurelle Biogel(®) (ZP-025) vaginal gel, which contains a purified, dialyzed, lyophilized bovine colostrum, in women of reproductive age suffering from vaginal dryness. DESIGN: Randomized clinical trial (RCT) (Z7213M01). SETTING: Five University Gynaecological Units. PATIENTS: Ninety-five subjects were allocated at random to receive either ZP-025 (n=48) for about 23 intermenstrual days (1 or 2 times/daily intra-vaginally) or no treatment (lubricants on demand were allowed). MAIN OUTCOME MEASURES: Change of Verbal Rating Scale (VRS) total and single score for vaginal symptoms, Vaginal Health Index (VHI) score, Female Sexual Function index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R) scores. RESULTS: A total number of 85 subjects was evaluable for primary analyses. Symptoms (VRS) of vaginal discomfort improved significantly already after 11 days, as compared to the control arm (p<0.0001). The mean VHI score was also significantly higher in ZP-025 group (p<0.001) at the end of the study. The analysis of covariance with the baseline value as covariate carried out on the FSFI Total Score showed a statistically significant difference in favour of the ZP-025 arm (p<0.032). A shift from presence to absence of sexual distress (≤11 points) was more prominent in the ZP-025 arm [10 subjects (40%) in the ZP-025 arm (p<0.0001) and 6 subjects (21.4%) in the control arm (p=0.01)]. Women reported a compliance rate of 100% for one ZP-025 application/day. Local tolerability of ZP-025 was excellent or good in 82.9% of the subjects. CONCLUSIONS: The present multicentre RCT supports the use of Monurelle Biogel(®) in women of reproductive age reporting symptoms of vaginal dryness. A positive impact on vaginal health and sexual function was also evident.

Variation in Nugent score and leukocyte count in fluid collected from different vaginal sites.

OBJECTIVE: To assess the variability in Nugent score and leukocyte count measured in vaginal secretions collected from 3 vaginal sites. METHODS: Fifty pregnant women at less than 20 weeks of gestation were consecutively recruited at the time of their first prenatal visit. Three vaginal smears were collected from each woman, 1 from the posterior fornix, 1 from the mid-lateral wall, and 1 from the introitus. Smears were Gram stained and evaluated for bacterial vaginosis using Nugent's criteria. Each smear was classified as positive for bacterial vaginosis if the Nugent score was 7 or greater, intermediate if the score was between 4 and 6, and negative if the Nugent score was 3 or less. A mean leukocyte value was obtained for each slide by evaluating 5 fields under oil immersion. Repeated-measures analysis of variance was used to compare mean Nugent scores and leukocyte counts across sites. RESULTS: The sample consisted of mostly African-American, young, low-income women in their first trimester of pregnancy. Forty-seven percent were bacterial vaginosis-positive (Nugent score 7 or greater). Mean Nugent scores (+/- standard deviation) across the vaginal sample collection sites were similar: posterior fornix = 4.2 (4.4); mid-lateral wall = 4.2 (4.5); introitus = 4.2 (4.6). In contrast, the mean leukocyte count varied significantly across vaginal sample collection sites: 2.5 (4.2); mid-lateral wall = 2.8 (4.4); introitus = 6.5 (8.6) (F = 11.26 (1, 47.5); P = .002). CONCLUSION: Leukocyte counts vary according to the site from which vaginal secretions were obtained, with the highest leukocyte count in samples obtained from the introitus. Bacterial vaginosis diagnosis by Nugent score does not vary by site of sample collection.

Italian multicentric pilot study on MBL2 genetic polymorphisms in HIV positive pregnant women and their children.

OBJECTIVE: We investigated genetic polymorphisms of MBL2 gene, in a cohort of 90 Italian HIV-1 pregnant seropositive women and their children in order to understand whether the MBL2 genotype of HIV-1 positive mothers might be related to their ability to transmit the virus to their children. MATERIALS AND METHODS: DNA was extracted from Iso Code Stix cards, and MBL2 genotyping was performed by Melting Temperature Assay. RESULTS: The frequency of the MBL2 0/0 homozygotes was higher in HIV-1 positive mothers than in healthy controls, the MBL2 0/0 genotype was more frequent in children born from HIV positive mothers than healthy subjects. CONCLUSIONS: We have confirmed the association of polymorphisms involving a gene of the innate immunity with an increased risk of being infected by HIV. These polymorphisms were also evidenced in children born from HIV+ mothers, but the risk of infection was strongly reduced by cesarean delivery and by antiretroviral treatment.