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Objective: Do metabolites in vaginal samples vary between women with different vaginal disorders.Design: Cross-sectional study.Setting: Campinas, Brazil.Sample: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV).Method: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test.Main Outcome Measures: Metabolite levels and their correlation with diagnoses.Results: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells.Conclusions: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to describe the vaginal microbiome of women with premature ovarian insufficiency (POI) receiving systemic hormone therapy (HT)., Methods: Forty women with POI receiving systemic HT for at least 6 months, who were sexually active, were included in the descriptive cross-sectional study. Vaginal secretion was collected for DNA extraction followed by pyrosequencing of the 16S rRNA. The samples were pooled into phylogenetic groups (Ravel groups I-V)., Results: Women had mean age of 37.13 (± 7.27) years and POI diagnosis at age 27.90 (± 8.68) years, and a mean HT duration of 8.20 (± 8.73) years. It was observed that 33.4% of the women presented group I flora, with a predominance of Lactobacillus crispatus ; 9% group II flora, with a predominance of Lactobacillus gasseri ; 33.4% group III flora, with a predominance of Lactobacillus iners ; 15.2% group IV flora, with a predominance of anaerobic bacteria; and 9% group V flora, with a predominance of Lactobacillus jensenii ., Conclusion: Women with POI receiving HT presented a vaginal microbiome with a predominance of lactobacilli in the composition of the vaginal flora, specifically L. crispatus and L. iners when evaluated by molecular biology through pyrosequencing of 16S rRNA.

Introduction and Hypothesis: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia., Methods: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat., Results: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04)., Conclusion: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up., (© 2023. The International Urogynecological Association.)

Objective: Vulvodynia (VVD) is a frequent and harrowing condition for which diagnosis and management remain insufficient. Our study aimed to describe and compare vulvovaginal signs and symptoms of Brazilian women with VVD and controls and describe previous medical assessment, past treatments, and vulvar pain relief among women with VVD., Methods: This cross-sectional descriptive study included Brazilian women with (n = 151) and without VVD (n = 106). All women were assessed for vaginal infection, vulvar pain intensity by means of a cotton swab test based on a numerical rate scale, and answered the Female Sexual Function Index questionnaire and a structured instrument about current vulvar symptoms. Previous treatments were assessed in the VVD group, and vulvar pain relief achieved with previous treatments was qualified through a 4-point Likert scale., Results: Volunteers were mainly White, with mean age of 30 years. Vulvovaginal signs and symptoms were significantly more frequent in women with VVD (p < .05), and vulvar pain duration was 5.8 (±4) years. More than 50% consulted with three or more physicians, and 49% remained without a conclusive diagnosis. Previous diagnosis and treatment of vulvovaginal infection were often reported by women with VVD. Most of the tried prescriptions were self-reported as providing only low vulvar pain relief., Conclusions: Prolonged duration of vulvar pain, multiple visits to health care professionals, and poor relief of pain are common aspects in the clinical history of women with VVD. In addition to pain, vulvar fissure, edema, erythema, vaginal discharge, and foul odor are common and should be considered to avoid misdiagnosis. Appropriate treatments to VVD are still poorly reported., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

Introduction and Hypothesis: To compare blood flow of the dorsal clitoral artery in women diagnosed with provoked vestibulodynia (PVD) and in healthy controls using color Doppler ultrasonography. We hypothesized that women with PVD would have a restricted blood flow compared to controls., Methods: This cross-sectional study evaluated the function of the dorsal clitoral artery through the spectral wave analysis of color Doppler ultrasonography (US) in 20 women diagnosed with PVD according to Friedrich's criteria and 21 healthy controls. Participants were evaluated during their follicular phase and were asked to abstain from sexual activities 24 ho prior the examination. Assessment was performed by an assessor blinded to participant diagnosis, in the morning after a 10-min rest period in a supine lying position in a room with temperature set at 22 °C. Measurements of the peak systolic velocity (PSV), time-averaged maximum velocity (TAMX), end-diastolic velocity (EDV), pulsatility (PI) and resistance index (RI) were performed at rest considering the mean value of three consecutive waveforms., Results: Women with PVD and healthy controls did not present any statistically different baseline characteristics. Participants with PVD presented higher values of Doppler-US PSV, TAMX, EDV and RI compared to controls (p ≤ 0.05), which are suggestive of a decrease in blood flow. However, non-significant difference was found regarding PI values between the two groups (p > 0.05)., Conclusion: Our findings revealed decreased peripheral tissue perfusion in women with PVD compared to healthy controls using color Doppler US, based on the alteration of four of the five assessed data of US parameters., (© 2022. The International Urogynecological Association.)

Objective:  To evaluate genital hygiene among women with and without bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC)., Methods:  A cross-sectional study of reproductive-aged women who underwent gynecological and laboratory tests and fulfilled a genital hygiene questionnaire., Results:  This study evaluated 166 healthy controls and 141 women diagnosed with either BV (n = 72), VVC (n = 61), or both (n = 8). The use of intimate soap and moist wipes after urination was more frequent among healthy women ( p  = 0.042 and 0.032, respectively). Compared to controls, bactericidal soap was more used by women with BV ( p  = 0.05)., Conclusion:  Some hygiene habits were associated to BV and/or VVC. Clinical trials should address this important issue in women's health., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Introduction: The influence of vaccination on composition of the human microbiome at distinct sites has been recognized as an essential component in the development of new vaccine strategies. The HPV vaccine is widely used to prevent cervical cancer; however, the influence of HPV vaccine on the vaginal microbiota has not been previously investigated. In his study, we performed an initial characterization of the microbiome and cytokine composition in the vagina following administration of the bivalent vaccine against HPV 16/18., Material and Methods: In this exploratory study, fifteen women between 18 and 40 years received three doses of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix®). Cervicovaginal samples were collected before the first dose and 30 days after the third dose. HPV genotyping was performed by the XGEN Flow Chip technique. The cytokines IFN-γ, IL-2, IL-12p70, TNF-α, GM-CSF, IL-4, IL-5, IL-10, and IL-13 were quantitated by multiplex immunoassay. The vaginal microbiome was identified by analysis of the V3/V4 region of the bacterial 16S rRNA gene., Results: The most abundant bacterial species in the vaginal microbiome was Lactobacillus crispatus, followed by L. iners. Bacterial diversity and dominant organisms were unchanged following vaccination. Small decreases in levels of pro and anti-inflammatory cytokines were observed following HPV vaccination, but there was no association between vaginal cytokine levels and microbiome composition., Conclusion: Vaginal microbiome is not altered following administration of the standard three-dose HPV-16/18 AS04-adjuvanted (Cervarix®) vaccine., (© 2021. Sociedade Brasileira de Microbiologia.)

Genitourinary syndrome of menopause (GSM) is a term used to define a compilation of signs and symptoms arising from decreased estrogenic stimulation of the vulvovaginal and lower urinary tract. Among 27-84% of women in postmenopausal are affected for symptoms of GSM, and these can unquestionably impair health, sexual function, consequently the quality of life of these women. The main signs and symptoms of GSM include, among others, burning, irritation, vulvovaginal dryness, dyspareunia, urinary symptoms of urgency, dysuria, or recurrent urinary tract infection. The diagnosis can be made through anamnesis, questionnaires, physical exams, and, sometimes, complementary exams. Objective vaginal assessment is essential and can be complemented by using the Vaginal Health Index (VHI), Vaginal Maturation Index (VMI), or vaginal pH measurement. The acknowledgment of this condition by health professionals is crucial for its identification and proper management and exclusion of other conditions that make a differential diagnosis with it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sarmento, Costa, Vieira-Baptista, Giraldo, Eleutério and Gonçalves.)

Introduction and Hypothesis: To evaluate the complications of new users' vaginal pessaries (VP), with and without the use of vaginal estrogen after a 6-month follow-up., Methods: A parallel, single-blinded, randomized, controlled trial. Symptomatic postmenopausal women (n = 98) with pelvic organ prolapse (POP) (stage 3/4) were recruited from August 2018 to October 2019. Patients were randomized into the local estrogen group (promestriene 3 × for a week) and the control group (no estrogen). They were evaluated for their vaginal symptoms at the baseline, after 3 months, and after 6 months, and a physical examination and vaginal sampling for microbiological analysis were done. Data were analyzed according to an intention-to-treat analysis (ITT). A 5% significance level was established for statistical analysis., Results: Twenty women discontinued treatment (20.4%), mainly due to pessary extrusion (n = 15) and 5 for other reasons (lost to follow-up, pain, and surgery). Baseline characteristics were not statistically different between the estrogen and control groups. Regarding the presence of complications, the presence of erosion was 10% in the control group, but there was no significant difference between the groups (p = 0.175) after 6 months. Bacterial vaginosis (BV) was more prevalent in the control group, according to the Nugent (p = 0.007) and Amsel (p = 0.014) criteria. Urinary urgency and increased urinary frequency were significantly improved in the estrogen group after 6 months., Conclusion: There was no evident benefit related to complications such as ulcerations, itching, and vaginal discharge/odor from the use of vaginal estrogen in POP women using pessaries.

Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an upper female genital tract acute infection due to canalicular spread of endogenous cervicovaginal microorganisms and especially the sexually transmitted microorganisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The main sequelae are chronic pelvic pain, infertility, and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment must start immediately after the clinical suspicion. Guidelines for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling sexual partners and special populations are described. Given the increased availability of the molecular biology techniques in Brazil, C. trachomatis and N. gonorrhoeae screening are recommended as a disease prevention strategy. Pelvic inflammatory disease is one of the most significant sexually transmitted infections, and in most cases, it is a main consequence of cervicitis.

Objective: The aim of the study was to evaluate the associated factors associated with pessary dislodgment in women with advanced pelvic organ prolapse (POP)., Methods: A cohort study with women (N = 98) with advanced POP who chose conservative treatment with ring pessary between December 2016 and 2018 identified by screening. Demographic data, history of POP, urinary, and/or bowel symptoms were collected. A medical visit was scheduled 3 and 6 months after pessary insertion to evaluate symptoms (vaginal discharge, bleeding, pain, discomfort, new-onset urinary, or fecal problems) and any pessary dislodgment. Two groups were created (women who were able to retain the pessary versus who were not able), and univariate and multivariate analysis were performed to look for risk factors for pessary dislodgment. Women who requested to have their pessaries removed during the 6-month follow-up were excluded., Results: Ninety-three women included in the study, 78 successfully continued to use the pessary at 6 months, and 15 had pessary dislodgment (16.1%). Demographic characteristics were similar between the treatment group and the control group. After multivariate analysis, women who had their pessaries dislodged presented higher rates of previous surgery (odds ratio = 8.11; 95% confidence interval = 2.09-31.58; P = 0.003) with advanced Pelvic Organ Prolapse Quantification system staging (odds ratio, 13.41; confidence interval, 1.97-91.36; P = 0.008)., Conclusions: The presence of advanced apical POP and previous POP surgery are risk factors for ring pessary dislodgment. This information should guide physicians for counseling patients before pessary insertion., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020 American Urogynecologic Society. All rights reserved.)

Objective: To assess the influence of the copper IUD and LNG-IUS on liquid-based cytology results (cellular atypia, reactive alterations, and microbiology)., Study Design: This cross-sectional study was performed between January 2012 and December 2017 in the Northeast of Brazil. Three study groups, the LNG-IUS group (n = 1179), copper IUD group (n = 519), and a control group of women not using contraception (n = 14,616) were compared. To facilitate this analysis, the LNG-IUS and IUD groups were further divided into less and more than two years of use., Results: The mean age of the LNG-IUS and IUD groups was around 36 years and the control group was about 35 years (p = ns). The meantime between dispositive placement and examination was 19 ± 16 months for the LNG-IUS and 17 ± 15 months for the IUD. The frequency of epithelial atypia revealed upon cytological analysis did not differ between the groups. However, inflammatory infiltrates were significantly more frequent in the LNG-IUS and IUD (OR IUD = 1.32; OR LNG-IUS = 1.79) groups relative to control. Candida and cytolysis were more frequent in the LNG-IUS group (OR = 4.73 and 2.41, respectively) compared to both other groups. Bacterial vaginosis andActinomyces sp occurred more frequently in the IUD group (OR = 1.39 and 3352.55, respectively) compared to both other groups. Bacterial vaginosis was more common when using an IUD for more than two years than for less than two years (OR = 2.55). The Actinomyces morphotype was also observed at greater frequency after two years of IUD use than before (OR = 5.35)., Conclusions: The LNG-IUS and copper IUD do not affect the incidence of cellular atypia but do interfere with the microbiota over time. Specifically, the copper IUD is associated with bacterial vaginosis andActinomyces sp infection while the LNG-IUS is associated with candidiasis and cytolysis., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Vulvodynia is a disabling condition in which pelvic floor muscles' (PFM) hypertonicity plays an important role., Aim: To evaluate biometric changes in PFM in women with vulvodynia undergoing kinesiotherapy treatment protocol (KTP)., Methods: A single-blinded randomized controlled trial of 57 women with vulvodynia randomly assigned to either KTP + amitriptyline or amitriptyline alone (controls) for treatment. Four-dimensional translabial ultrasound assessed PFM regarding symphysis-levator distance at rest, anorectal angle at rest, excursion of the levator plate angle, and levator hiatal narrowing. Volunteers underwent a vaginal examination for a cotton swab test (CST), fulfillment of Friedrich criteria score and PFM power of contraction, and completed a diary of sexual pain and frequency of vaginal intercourse. Outcomes were assessed at baseline and after 8 weeks of treatment., Outcomes: Primary outcomes were differences in biometric parameters assessed by four-dimensional translabial ultrasound after treatment, between groups. Secondary outcomes were changes in clinical variables (CST, Friedrich criteria, PFM power of contraction, frequency of intercourse, and intensity of sexual pain) between groups and correlation analysis between biometric parameters and clinical variables., Results: Only the KTP group had statistically significant changes in biometric parameters after treatment (symphysis-levator distance: 0.22 ± 0.2, 95% CI = 0.1-0.4, P = .008; levator hiatal narrowing: -0.33 ± 0.2, 95% CI = -1 to -0.2, P = .04). Comparisons between groups showed that symphysis-levator distance (0.3, 95% CI = 0.2-0.6, P = .005) and excursion of levator plate angle (4.9, 95% CI = -0.4 to 10.1, P = .02) improved significantly after KTP treatment. Clinical variables showed greater improvement in the group treated with KTP for CST (difference of -3.7, 95% CI = -7 to -0.4, P = .01), Friedrich criteria (difference of -1.9, 95% CI = -3.2 to -0.6, P = .003), PFM power of contraction (0.3, 95% CI = 0.1-0.6, P = .05) and intensity of sexual pain (reduction of 1.7, 95% CI = -3.1 to -0.2, P = .01). Some clinical and biometric variables correlated positively, for example, frequency of vaginal intercourse and anorectal angle (P = .04; r = 0.25), or inversely, for example, pain intensity at CST and anorectal angle (P = .004, r = -0.31)., Clinical Implications: This study provides evidence on efficiency of a physical therapy protocol for improvement of symptoms of vulvodynia and hypertonicity changes., Conclusion: This pilot study suggests that KTP for women with vulvodynia promoted significant changes in PFM biometric measures, consistent with alterations in hypertonicity and clinical improvement. Bardin MG, Giraldo PC, Martinho N. Pelvic Floor Biometric Changes Assessed by 4D Translabial Ultrassound in Women With Vulvodynia Submitted to Physical Therapy: A Pilot Study of a Randomized Controlled Trial. J Sex Med 2020;17:2236-2246., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective:  To identify clinical, microscopic, and biochemical characteristics that differentiate cytolytic vaginosis (CV) from vulvovaginal candidiasis (VVC)., Methods:  The present cross-sectional study analyzed the vaginal contents of 24 non-pregnant women aged 18 to 42 years who were attended at the Genital Infections Clinic at Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). They were diagnosed either with (CV = 8, VVC = 8) or without vulvovaginitis or vaginal dysbiosis (controls). The socio-demographic, clinical, and gynecological data were obtained from a detailed patient interview. Samples of the vaginal contents were collected for analysis of vaginal pH, gram stain, and specific fungal culture. The Kruskal-Wallis and Fisher exact tests were used to compare the differences between the groups. Odds ratios were used to compare the categorical variables. The significance level was considered at p  < 0.05., Results:  Both women with CV and VVC had a lumpy vaginal discharge ( p  = 0,002) and vaginal hyperemia ( p  = 0.001), compared with controls. The inflammatory process was more intense in the VVC group ( p  = 0.001). In the CV group, there was statistical significance for the lactobacillus amount ( p  = 0.006), vaginal epithelium lysis ( p  = 0.001), and vaginal pH ( p  = 0.0002)., Conclusion:  Cytolytic vaginosis and VVC diagnoses rarely differ on clinical characteristics but have different laboratorial findings. The present study highlights the importance of conducting an accurate investigation through laboratory tests rather than clinical criteria to avoid misdiagnosis., Competing Interests: The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: The aim of the study was to describe the course of IgG/IgA immune response in women immunized with bivalent vaccine and in women non-vaccinated with HPV infection, as well as evaluating the cross-protection against non-vaccine HPV types., Methods: Serum and cervical mucus samples were collected from infected and vaccinated women for HPV detection/genotyping and for detection of IgG/IgA anti-HPV/VLP (Virus-like Particles) by ELISA., Results: The median absorbance detected in serum samples for anti-HPV-IgG antibodies was higher in vaccinated women when compared to HPV infected women (p <0.01), however, the median absorbance in cervical mucus samples for anti-HPV-IgA was higher in infected women when compared to vaccinated women (p <0.01). Additionally, our analyses also provided additional evidence for cross-protective efficacy of the HPV-16/18 vaccine against HPV-82, -6, -11, -13, -61, -72 and -74., Conclusion: The IgG antibodies were significantly more detected in the serum of vaccinated women, while the IgA was found in greater quantities in cervical samples from those infected by the virus. In addition, there is evidence that the bivalent vaccine provides cross-protection against other non-oncogenic viral subtypes., .

Background: Composition of the vaginal microbiome is strongly related to a woman's reproductive health and risk of sexually transmitted infections. Ethnoracial, behavioral, and environmental factors can influence microbiome. The Brazilian population is unique in terms of miscegenation of ethnic groups and behavioral characteristics across different regions. We aimed to characterize the vaginal microbiome of women from 5 geographical regions of Brazil., Methods: We sequenced V3-V4 regions of 16S rRNA gene in vaginal samples of 609 reproductive-aged women. We performed logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between sociodemographic and behavioral factors with Lactobacillus-depleted microbiome (community state type [CST] IV)., Results: Vaginal samples were grouped into 5 CST: CST I (L. crispatus predominant, 30.5%), CST II (L. gasseri predominant, 4.4%), CST III (Lactobacillus iners predominant, 36.5%), CST IV (Lactobacillus-depleted, 27.4%), and CST V (L. jensenii predominant, 1.2%). Several factors were independently associated with CST IV, such as smoking (OR, 1.80; 95% CI, 1.02-3.18), number of partners (OR, 2.11; 95% CI, 1.20-3.70), and vaginal douching (OR, 2.24; 95% CI, 1.34-3.74). A protective effect was observed for milk/dairy intake (OR, 0.47; 95% CI, 0.27-0.82) and sitz bathing (OR, 0.43; 95% CI, 0.19-0.98)., Conclusions: Nearly two thirds of Brazilian women may be at an increased risk for adverse outcomes associated with a vaginal microbiota characterized by the depletion of Lactobacillus or dominance by L. iners, whose protective role has been widely questioned. Several factors related to sexual behavior and intimate hygiene were associated with CST IV.

Objectives: We aimed to evaluate the effectiveness of microablative fractional radiofrequency (MAFRF) in the non-hormonal treatment of genitourinary syndrome of menopause., Methods: We examined the cases of 55 postmenopausal women before and after treatment with regard to their vaginal health index (VHI), vaginal microbiota, vaginal pH, and cell maturation. Three applications of MAFRF were performed in the vagina/vaginal introitus. During the treatment, six vaginal smears were obtained and stained with the Papanicolaou stain for determining the degree of cell maturation and with Gram stain for classification of vaginal flora, as per the criteria of Spiegel and Amsel. For vaginal pH determination, pH indicator strips were applied against the vaginal wall. Statistical analysis was performed using SPSS for Windows (version 17.0). Data were reported as mean±standard deviation. The differences were analyzed using the statistical method of generalized estimation equations with autoregressive correlation structure "1" and robust standard errors., Results: The mean age was 59.8±4.2 years, and the mean time of menopause was 15.4±4.5 years. After treatment, there was an increase in the percentage of Lactobacillus spp. (p<0.001). Consequently, there was a progressive decrease in vaginal pH during the treatment (p<0.001). Regarding cell maturation, there was a decrease in the percentage of parabasal cells (p=0.001) and an increase in the rate of superficial cells (p<0.001). Additionally, there was an improvement in the VHI index. The mean VHI values before and after treatment were 13.2±5.6 and 22.5±3.7, respectively (p<0.001)., Conclusion: MAFRF treatment is well tolerated and leads to improvement in the vaginal microenvironment.

Background: There is a high frequency of human papillomavirus (HPV)-induced lesions in cervix and anus of immunosuppressed patients. However, few studies have evaluated these lesions in kidney-transplanted women., Methods: This cross-sectional study examined 31 kidney-transplanted women receiving immunosuppressive therapy at the General Hospital of Fortaleza in Brazil. Cervical and anal samples were collected and preserved in order to perform liquid-based cytology and a real-time polymerase chain reaction assay detecting high-risk HPV., Results: The patients' ages ranged from 31 to 70 years (mean: 42.6 ± 10.4). The age of sexual debut varied from 14 to 30 years (mean: 19.7 ± 3.8). Cervical cytology was diagnosed as atypical in 25.8% of cases (atypical squamous cells of undetermined significance [ASC-US] in 2 [6.2%], atypical squamous cells, but unable to exclude a high-grade squamous intraepithelial lesion in 1 [3.1%], low-grade squamous intraepithelial lesion [LSIL] in 4 [12.4%], and squamous cell carcinoma in 1 [3.1%]). Anal cytology was atypical in 35.4% of cases (ASC-US in 1 [3.2%] and LSIL in 7 [21.7%]). The presence of cervical HPV was confirmed in 22.5% of patients, and anal HPV was found in 48.8% of the cases. The relative risk of atypical anal cytology in cases of atypical cervical cytology was 4.37 (1.35-14.20). High-risk cervical HPV did not significantly increase the risk of having atypical anal cytology. However, for HPV in the anus, this was associated with a relative risk of 10.18 (1.45-71.54)., Conclusion: High-risk HPV and atypical cytology are very common in the cervix and anus of kidney-transplanted women. Furthermore, the presence of HPV in an anal sample correlates with an increased risk of atypical anal cytology. HPV tests could be useful tools for identifying patients who require anal cytology., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS)., Methods: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed., Results: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size., Conclusions: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.

Objective: The vaginal flora from postmenopausal women with pelvic organ prolapse (POP) is different from younger women. We hypothesized that the decision of a surgical route using a mesh would modify the vaginal flora. The purpose of this study was to analyze the vaginal flora from postmenopausal women that were submitted to abdominal sacrocervicopexy or vaginal sacrospinous fixation., Methods: A pilot, randomized controlled study with 50 women aged 55 to 75 years (n = 25; abdominal sacrocervicopexy + subtotal hysterectomy; n = 25 vaginal sacrospinous fixation + vaginal hysterectomy) was performed. A polyvinylidene mesh was used in both arms. The vaginal content analysis was collected before and 60 days after the surgery. The type of flora, the presence of lactobacilli/leukocytes, and the Nugent criteria were analyzed., Results: Most of the women were white (80%), with at least 1 comorbidity (69.9%), did not present sexual activity (60%), and presented advanced stage 4 POP. Two thirds of women presented a type 3 flora, and half of them did not present lactobacilli (48.3%). About the Nugent criteria, 51.7% presented normal flora, 46.6% found altered flora, and 1.7% had bacterial vaginosis. There were no differences about the type of flora (P = 1), number of lactobacilli (P = 0.9187), Nugent criteria (P = 0.4235), inflammation (P = 0.1018), and bacterial vaginosis (P = 0.64) before and after surgery in both groups., Conclusions: In this pilot study, the use of synthetic mesh by vaginal or abdominal route did not affect the vaginal flora in postmenopausal women operated on by POP surgery.

Introduction: Vulvovaginal candidiasis (VVC) is frequent in women worldwide and usually responds rapidly to topical or oral antifungal therapy. However, some women develop recurrent vulvovaginal candidiasis (RVVC), which is arbitrarily defined as four or more episodes every year. RVVC is a debilitating, long-term condition that can severely affect the quality of life of women. Most VVC is diagnosed and treated empirically and women frequently self-treat with over-the-counter medications that could contribute to an increase in the antifungal resistance. The effective treatment of RVVC has been a challenge in daily clinical practice. This review aims to assess the efficacy of antifungal agents administered orally or intravaginally for the treatment of RVVC, in order to define clinical practices that will impact on the reduction of the morbidity and antifungal resistance., Methods and Analysis: A comprehensive search of the following databases will be carried out: PubMed, Embase, Scopus, Web of Science, Scientific Electronic Library Online (SciELO), the Cochrane Central Register of Controlled Trials (CENTRAL), Biblioteca Virtual em Saúde (Virtual Health Library)/Biblioteca Regional de Medicina (Regional Library of Medicine) (BVS/BIREME), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and in the clinical trials databases (www.trialscentral.org; www.controlled-trials.com; www.clinicaltrials.gov). The risk of bias will be assessed according to the Cochrane Risk of Bias tool. We will perform data synthesis using the Review Manager (RevMan) software V.5.2.3. To assess heterogeneity, we will compute the I2 statistic., Ethics and Dissemination: This study will be a review of published data and it is not necessary to obtain ethical approval. Findings of this systematic review will be published in a peer-reviewed journal., Trial Registration Number: CRD42018093817., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Genital hygiene can play an essential role in avoiding vulvovaginal discomfort and preventing infections. The scientific evidence on best practices on genital hygiene is scarce, and without doubt, gynecologists should be the best person to discuss and guide the subject., Objective: Evaluate the general genital female gynecologist hygiene., Methods: This descriptive analytic study identified genital hygiene and sexual practices of 220 female gynecologists, through a questionnaire with 60 self-answered questions. The data were analyzed and presented using frequency, percentage, mean and standard deviation., Results: The studied population was constituted by middle age (37.3 years) and white (71.3%) female gynecologists. More than a half (53.6%) declared spending over 10 hours a day away from home and complained of vaginal discharge in 48.1% of the cases. Regular vulvovaginal hygiene: 17.8% reported washing genitals once a day and 52% twice a day. The use of dry paper alone was reported in 66.4% post urination and 78.5% post-evacuation. Using running water and soap was practiced by 25.9% and 21.5% respectively. Vulvovaginal hygiene related to sex: More than half of them had intercourse 1-3 times a week, and 37.4% and 24.1% had frequent oral sex and eventually anal sexof the participants, respectively. Genital hygiene before sex was positive in 52.7% of the subjects and, post-sex hygiene in 78.5% of them., Conclusion: Genital hygiene habits of female gynecologists can be improved, despite the high grade of scientific knowledge they hold.

Objective: To identify the factors associated with the prescription of vaginal pessaries (VPs) as a conservative treatment for pelvic organ prolapse (POP)., Methods: A cross-sectional study was performed during two annual urogynecology and general obstetrics and gynecology meetings in 2017 (São Paulo, SP, Brazil). A 19-item deidentified questionnaire regarding experiences and practices in prescribing VPs for POP patients was distributed among gynecologists. Our primary outcome was the frequency of prescribing VPs as a conservative treatment for POP. The reasons for prescribing or not prescribing VPs were also investigated. Univariate and multivariate analyses with crude and adjusted odds ratios (ORs) were performed for variables associated with the prescription of pessaries., Results: Three hundred forty completed surveys were analyzed. Half of the respondents (53.53%) were between 30-49 years old; most of them were female (73.53%), were from the Southeast Region (64.12%), were trained in obstetrics and gynecology (80.24%) or urogynecology (61.18%) and worked in private offices (63.42%). More than one-third (36.48%) attended four or more POP cases/week, and 97.65% (n=332) had heard or knew about VPs for POP; however, only 47.06% (n=160) prescribed or offered this treatment to patients. According to the multivariate analysis, physicians aged 18-35 years (OR=1.97[1.00-3.91]; p=0.04), those who participated in a previous urogynecology fellowship (OR=2.34[1.34-4.09]; p<0.01), those with relatively high volumes of POP cases (4 or +) (OR=2.23[1.21-4.47]; p=0.01) and those with PhD degrees (OR=2.75[1.01-7.54]; p=0.05) prescribed more pessaries., Conclusions: Most gynecologists did not prescribe VPs. Younger physician age, participation in a previous urogynecology fellowship, a PhD degree, and a relatively high volume of POP cases were associated with increased VP prescription rates.

Objective: This study was designed to describe the course of IgG/IgA responses in cervical secretions and in serum one year after the first dose of intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. Methods: Blood and cervical mucus samples were collected for immunologic assays, 7 months after the first doses and 1 year following the last boost vaccination (month 7) by enzyme linked immunosorbent assay (ELISA). The detection of IgG and IgA anti-HPV/VLP was developed for this purpose. Result: A total of 100% of serum samples were IgG antibody positive at a titer of 1:100 at both time periods and decreased according to the serum dilution. For serum IgA antibody, 95% were positive one month after vaccination and 79% were positive 1 year later. Similar results were observed with the cervical samples positive for both IgG and IgA antibodies at one month and decreasing after 1 year to 33% and 29%. The median absorbance in serum and the cervix for IgG and IgA anti-HPV-VLP antibodies was significantly higher at one month after vaccination when compared to 1 year post-vaccination (P<0.0001). Conclusion: Immune responses were significant one year after immunization, however it decreased in cervical and serum samples when compared to levels observed one month after the last dose. This suggests that a vaccine booster may be necessary to increase antibody titers., (Creative Commons Attribution License)

Objective: To characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis., Design: Cross-sectional study., Setting: Genital Infections Ambulatory, Department of Tocogynecology, University of Campinas, Campinas, São Paulo-Brazil., Sample: Twenty-four women were included in this study: eight with vulvovaginal candidiasis, eight with cytolytic vaginosis and eight with no vaginal infections or dysbiosis (control group)., Methods: The lipid profile in vaginal discharge of the different study groups was determined by liquid chromatography-mass spectrometry and further analyzed with MetaboAnalyst 3.0 platform., Main Outcome Measures: Vaginal lipids concentration and its correlation with vulvovaginal candidiasis and cytolytic vaginosis., Results: PCA, PLS-DA and hierarchical clustering analyses indicated 38 potential lipid biomarkers for the different groups, correlating with oxidative stress, inflammation, apoptosis and integrity of the vaginal epithelial tissue. Among these, greater concentrations were found for Glycochenodeoxycholic acid-7-sulfate, O-adipoylcarnitine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group; N-(tetradecanoyl)-sphinganine, DL-PPMP, 1-oleoyl-cyclic phosphatidic, palmitic acid and 5-aminopentanoic acid in the cytolytic vaginosis group; and 1-nonadecanoyl-glycero-3-phosphate, eicosadienoic acid, 1-stearoyl-cyclic-phosphatidic acid, 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphate, formyl 9Z-tetradecenoate and 7Z,10Z-hexadecadienoic acid in the control group., Conclusions: Lipids related to oxidative stress and apoptosis were found in higher concentrations in women with vulvovaginal candidiasis and cytolytic vaginosis, while lipids related to epithelial tissue integrity were more pronounced in the control group. Furthermore, in women with cytolytic vaginosis, we observed higher concentrations of lipids related to bacterial overgrowth., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests., Study Design: A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results., Results: An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370)., Conclusion: ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology., (© 2017 S. Karger AG, Basel.)

Objective: The aim of this work was to evaluate 100% rapid review (100% RR) as a useful tool to detect false negative (FN) results., Study Design: A sample of 8,677 swabs was investigated; the unsatisfactory and negative results were referred to 100% RR, concordant results were taken as the final diagnosis, while the discordant results were debated in a consensus meeting to reach a conclusion. The positive results were examined by 2 cytologists. The data were entered into SAS statistical software, and the agreement of the 100% RR results with the final diagnosis was tested with the weighted kappa statistic., Results: There was a significant increase in unsatisfactory results from 348 to 1,927, and of positive results from 174 to 349. On the other hand, there was a substantial decrease in negative results from 8,155 to 6,401. Assessing the relative risk of FN results in smears that were not referred to quality control (100% RR) revealed the following results: atypical squamous cells of undetermined significance (ASC-US), 2.93; low-grade squamous intraepithelial lesion (LSIL), 2.72; high-grade squamous intraepithelial lesion/atypical squamous cells - cannot exclude HSIL (HSIL/ASC-H), 2.25. Evaluating by age group, a higher risk for LSIL (4.90) and ASC-US (3.85) was observed in patients aged under 25 years, whereas patients between 25 and 64 years and those over 64 years presented a higher risk for HSIL and ASC-H: 2.46 and 2.75, respectively., Conclusion: 100% RR is an effective screening tool for FN results in countries where molecular tests for DNA-HPV and prophylactic vaccines are not available in cervical cancer screening programs., (© 2018 S. Karger AG, Basel.)

Background: Bacterial vaginosis (BV) remains an enigmatic question. The term "osis" instead of "itis" is used because commonly, there are no inflammatory process associated with BV. However, leukocytes are often observed in it., Methods: In a transversal study, we evaluated 1178 cases with diagnosis of BV by liquid-based cytology (more than 20% of clue cells), attended in general gynecologic private clinic. Depending of the presence of more than five leukocytes on average per field in immersion objective (1000×), the cases were divided in two groups: few or no leukocytes (< 5 leukocytes per field) (BV) and with leukocytes (≥ 5 leukocytes per field) (BV-L). The Fisher exact and Student t tests was applied to a confidence interval of 95%. The project was approved by the Ethic Committee of Federal University of Ceará, Brazil., Results: The age between the groups was the only different socio-demographic variable. The assessment of vaginal discharge aspect had no characteristic aspect. Colposcopy findings suggesting colpitis and ectopy were more frequent in the group of BV-L, 7.1% and 6.9%, respectively. The study of the microbiology demonstrated in the BV-L group, more frequently co-occurrence of Candida sp (15.1%) than in BV group (1.5%) (P < .0001). The cellular atypia was present more frequently in the BV-L (9.6%) than in BV (5.7%) (P = .0116)., Conclusion: The presence of leukocytes in BV (or BV-L) may suggest a mixed infection, ectopy influencing the vaginal milieu and even epithelial atypia., (© 2017 Wiley Periodicals, Inc.)

Objective: To evaluate the influence of functional capacity (FC) and how it affects quality of life (QoL) in breast cancer survivors., Method: A total of 400 breast cancer survivors were studied - 118 without metastasis, 160 with locoregional metastasis and 122 with distant metastasis. The European Organization for Research and Treatment for Cancer Quality of Life Questionnaire--Core 30 (EORTC QLQ-C30), Breast Cancer-Specific (EORTC QLQ-BR23), and the Karnofsky Performance Scale (KPS) were used to evaluate FC and QoL., Results: Women with distant metastases presented lower KPS 75.3 (SD=12.5) (p<0.001). For QLQ-C30, the mean of the Functional Scale for patients with distant metastasis was 57 (SD=19) (p<0.001), and the mean of the Symptom Scale for patients with distant metastasis was 37 (SD=20) (p<0.001). Both the scales for pain and fatigue showed the highest mean in the groups. For the Global Health Scale, patients without metastasis scored a mean of 62 (SD=24) points, while those with locoregional metastases scored a mean of 63 (SD=21.4), and distant metastasis scored 51.3 (SD=24) points. In the group with distant metastases, 105 (87%) had pain, and the average KPS was 74 (SD=12.0) (p=0.001)., Conclusion: Breast cancer was associated with decreased FC, compromised QoL in women with locoregional and distant metastases compared to those without metastasis.

From the discovery of the Zika virus (ZIKV) in 1947 in Uganda (Africa), until its arrival in South America, it was not known that it would affect human reproductive life so severely. Today, damage to the central nervous system is known to be multiple, and microcephaly is considered the tip of the iceberg. Microcephaly actually represents the epilogue of this infection's devastating process on the central nervous system of embryos and fetuses. As a result of central nervous system aggression by the ZIKV, this infection brings the possibility of arthrogryposis, dysphagia, deafness and visual impairment. All of these changes of varying severity directly or indirectly compromise the future life of these children, and are already considered a congenital syndrome linked to the ZIKV. Diagnosis is one of the main difficulties in the approach of this infection. Considering the clinical part, it has manifestations common to infections by the dengue virus and the chikungunya fever, varying only in subjective intensities. The most frequent clinical variables are rash, febrile state, non-purulent conjunctivitis and arthralgia, among others. In terms of laboratory resources, there are also limitations to the subsidiary diagnosis. Molecular biology tests are based on polymerase chain reaction (PCR) with reverse transcriptase (RT) action, since the ZIKV is a ribonucleic acid (RNA) virus. The RT-PCR shows serum or plasma positivity for a short period of time, no more than five days after the onset of the signs and symptoms. The ZIKV urine test is positive for a longer period, up to 14 days. There are still no reliable techniques for the serological diagnosis of this infection. If there are no complications (meningoencephalitis or Guillain-Barré syndrome), further examination is unnecessary to assess systemic impairment. However, evidence is needed to rule out other infections that also cause rashes, such as dengue, chikungunya, syphilis, toxoplasmosis, cytomegalovirus, rubella, and herpes. There is no specific antiviral therapy against ZIKV, and the therapeutic approach to infected pregnant women is limited to the use of antipyretics and analgesics. Anti-inflammatory drugs should be avoided until the diagnosis of dengue is discarded. There is no need to modify the schedule of prenatal visits for pregnant women infected by ZIKV, but it is necessary to guarantee three ultrasound examinations during pregnancy for low-risk pregnancies, and monthly for pregnant women with confirmed ZIKV infection. Vaginal delivery and natural breastfeeding are advised., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Introduction  Vaginal pessary is used as a conservative treatment for pelvic organ prolapse (POP). Some studies have shown that common complaints of its use may include vaginal discomfort and increased vaginal discharge. Scant information is available about the microflora status after using this device. Objective  To determine if the usage of vaginal pessary can interfere with the vaginal environment. Methods  A cross-sectional study was performed from March of 2014 to July of 2015 including 90 women with POP. The study group was composed of 45 women users of vaginal pessary and 45 nom-users. All enrolled women answered a standardized questionnaire and were subjected to a gynecological exam to collect vaginal samples for microbiological evaluation under optic microscopy. Clinical and microbiological data were compared between study and control groups. Results  Vaginal discharge was confirmed in 84% of the study group versus 62.2% in the control group ( p  < 0.01); itching was reported in 20 and 2.2%, respectively ( p  < .05); genital ulcers were only found in the pessary group (20%). There was no difference with regard to the type of vaginal flora. Bacterial vaginosis was prevalent in the study group (31.1% study group versus 22.2% control group), ( p  =.34). Conclusion  Women using vaginal pessaries for POP treatment presented more vaginal discharge, itching and genital ulcers than non-users., (Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Objective: The aim of this study was to evaluate the 100% rapid review (100%-RR) as an effective tool for internal quality control (IQC) in gynecological cytopathology services., Study Design: A total of 8,677 swabs were analyzed; the negative results were submitted to 100%-RR. Divergent cases were discussed in a consensus meeting to reach a conclusion on the final diagnosis. The data were entered into SAS statistical software, and the agreement of the 100%-RR results with the final diagnosis was tested with the weighted kappa statistic., Results: Of the 8,155 smears characterized as negative, 255 (3.13%) were abnormal smears, and 552 (6.77%) unsatisfactory smears were deemed negative. Regarding the results on the 8,155 smears subjected to 100%-RR when compared with the final diagnosis, there was agreement in 7,063 (86.60%) of them, and there were 1,092 (13.40%) discordant results (65.6%, unsatisfactory; 5.47%, atypical squamous cells of undetermined significance [ASC-US]). The κ index had an agreement of 0.867, with κ = 0.734 (p < 0.0001). Compared with the final diagnosis, the sensitivity of 100%-RR was 99.91% and its specificity was 99.4% for severe abnormalities. The sensitivity for high-grade squamous intraepithelial lesions was 88.2%, with a specificity of 100.00%. For abnormalities considered borderline, such as ASC-US, the sensitivity was 94.50% and the specificity was 99.5%., Conclusion: The 100%-RR was considered efficient when used as an IQC method., (© 2017 S. Karger AG, Basel.)

Vaccination against human papillomavirus (HPV) has been progressively implemented in most developed countries for approximately 10 years. In order to increase the protection of the vaccines, a 9-valent vaccine (HPV9) was developed, which provides protection against nine types of the virus. Studies evaluating its safety are rare. Thus, we performed a meta-analysis of three clinical trials assessing adverse effects on women randomly vaccinated with HPV9 or tetravalent vaccine (HPV4), with the objective of analyzing whether the HPV9 is as safe as HPV4. An electronic data search was performed through the PubMed, Embase, Scopus, Web of Science, and SciELO databases. The studies selected 27,465 women who received one of the two vaccines. Pain (OR 1.72; 95% CI 1.62-1.82) and erythema (OR 1.29; 95% CI 1.21-1.36) occurred significantly more in the HPV9 group. However, there was no significant difference between the groups for the following adverse effects: headache (OR 1.07; 95% CI 0.99-1.15), dizziness (OR 1.09; 95% CI 0.93-1.27), and fatigue (OR 1.09; 95% CI 0.91-1.30), and the occurrence of serious events related to vaccination was similarly rare among those vaccinated. Therefore, our findings demonstrate that HPV9 in female patients is as safe as the tetravalent vaccine.

The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise) was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64). Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5%) had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR=2.46; p=0.03). In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR=2.81; p=0.02). This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Background: Individuals receiving the human papillomavirus (HPV) vaccine develop high levels of circulating neutralizing antibodies. However, data about antibody responses in the cervix are limited., Methods: This study was designed to describe the course of IgA/IgG responses in cervical secretions and in serum after intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. An enzyme-linked immunosorbent assay for detection of IgA and IgG anti-HPV-VLP was developed for this purpose., Results: Immunoglobulin G seroconversion after the second dose was observed in 100% of the participants and remained 1 month after the third dose. Regarding IgG reactivity in cervical secretions, conversion was observed in 85% of women after the final dose. Immunoglobulin A seroconversion was observed in 76.7% of women after the third dose. Lower levels of IgA were detected in the cervical mucus (28.3%) and decreased to 23.3% after the last dose. Comparing local and systemic IgG responses, positivity in both serum and cervical samples was observed in 85%, whereas in 15% only, the serum was IgG antibody positive. A weak agreement between local and systemic IgA responses was observed. Only 18.3% of participants were local and systemic IgA positive, 58.4% were positive only in serum, 5% were positive only in the cervix, and 18.3% were both local and systemic IgA antibody negative., Conclusions: After the third vaccination, there is a strong agreement between cervical and systemic IgG antibody responses and a weak agreement between cervical and systemic IgA antibody responses. The induction of IgA antibodies seems to be secondary to that of IgG antibodies in response to HPV intramuscular vaccination.

Problem: A wide variety of mediators are involved in inflammatory processes. However, the identity of those participating in vaginal immune responses has not been established. We correlated extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-8 (MMP-8), hyaluronan (HA), hyaluronidase-1 (Hyal-1), human β-defensin-2 (hBD2), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations with the extent of leukocyte infiltration into the vagina and suggest their participation in vaginal inflammation., Methods of Study: Vaginal fluid was obtained from 233 women seen at the outpatient clinic in the Department of Obstetrics and Gynecology at Campinas University, Brazil. The magnitude of vaginal inflammation was determined by the leukocyte count on vaginal smears and categorized as no inflammation (0 leukocytes/field), moderate inflammation (1-4 leukocytes/field), and intense inflammation (>4 leukocytes/field). Concentrations of EMMPRIN, MMP-8, HA, Hyal-1, hBD2, and NGAL were determined in vaginal fluid by ELISA., Results: EMMPRIN, MMP-8, HA, hBD2, and NGAL concentration increased with elevated leukocyte numbers (P < 0.05), while Hyal-1 did not. EMMPRIN concentrations were correlated with HA and MMP-8 levels., Conclusion: EMMPRIN, MMP-8, HA, β-defensin, and NGAL are elevated in women with vaginal inflammation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Evaluate TENS effectiveness as a complementary treatment of chronic pelvic pain and deep dyspareunia in women with deep endometriosis., Study Design: This randomized controlled trial was performed in a tertiary health care center, including twenty-two women with deep endometriosis undergoing hormone therapy with persistent pelvic pain and/or deep dyspareunia. This study was registered in the Brazilian Record of Clinical Trials (ReBEC), under n RBR-3rndh6. TENS application for 8 weeks followed a randomized allocation into two groups: Group 1 - acupuncture-like TENS (Frequency: 8Hz, pulse duration: 250μs) - VIF (n=11) and Group 2 - self-applied TENS (Frequency: 85Hz, pulse duration: 75μs) (n=11). The intensity applied was "strong, but comfortable". We evaluated patients before and after treatment by the use of the Visual Analogue Scale, Deep Dyspareunia Scale and Endometriosis Quality of Life Questionnaire. We used the Wilcoxon and Mann-Whitney tests to compare before and after treatment conditions., Results: Despite the use of hormone therapy for 1.65±2.08 years, the 22 women with deep endometriosis sustained pelvic pain complaints (VAS=5.95±2.13 and 2.45±2.42, p<.001) and/or deep dyspareunia (DDS=2.29±0.46 and 1.20±1.01, p=.001). We observed significant improvement for chronic pelvic pain, deep dyspareunia and quality of life by the use of TENS. Both application types of TENS were effective for improving the evaluated types of pain., Conclusions: Both resources (acupuncture-like TENS and self-applied TENS) demonstrated effectiveness as a complementary treatment of pelvic pain and deep dyspareunia, improving quality of life in women with deep endometriosis regardless of the device used for treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Vaginal glycogen is degraded by host α-amylase and then converted to lactic acid by Lactobacilli. This maintains the vaginal pH at ≤4.5 and prevents growth of other bacteria. Therefore, host α-amylase activity may promote dominance of Lactobacilli. We evaluated whether the α-amylase level in vaginal fluid is altered in women with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) and whether its concentration was associated with levels of lactic acid isomers and host mediators. Vaginal fluid was obtained from 43 women with BV, 50 women with VVC, and 62 women with no vulvovaginal disorders. Vaginal fluid concentrations of α-amylase, secretory leukocyte protease inhibitor (SLPI), hyaluronan, hyaluronidase-1, β-defensin, and elafin were measured by enzyme-linked immunosorbent assay (ELISA). Vaginal concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 8, and d- and l-lactic acid levels in these patients were previously reported. The median vaginal fluid α-amylase level was 1.83 mU/mL in control women, 1.45 mU/mL in women with VVC, and 1.07 mU/mL in women with BV. Vaginal levels of α-amylase were correlated with d-lactic acid (P = .003) but not with l-lactic acid (P > .05) and with SLPI (P < .001), hyaluronidase-1 (P < .001), NGAL (P = .001), and MMP-8 (P = .005). The exfoliation of glycogen-rich epithelial cells into the vaginal lumen by hyaluronidase-1 and MMP-8 may increase glycogen availability and promote α-amylase activity. The subsequent enhanced availability of glycogen breakdown products would favor proliferation of Lactobacilli, the primary producers of d-lactic acid in the vagina. Concomitant production of NGAL and SLPI would retard growth of BV-related bacteria., (© The Author(s) 2015.)

Objective: Do metabolites in vaginal samples vary between women with different vaginal disorders., Design: Cross-sectional study., Setting: Campinas, Brazil., Sample: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV)., Method: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test., Main Outcome Measures: Metabolite levels and their correlation with diagnoses., Results: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells., Conclusions: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is a component of innate immunity that prevents iron uptake by microorganisms. We evaluated whether NGAL was present in vaginal fluid and whether concentrations were altered in women with bacterial vaginosis (BV) or vulvovaginal candidiasis (VVC)., Methods: Vaginal secretions from 52 women with VVC, 43 with BV, and 77 healthy controls were assayed by enzyme-linked immunosorbent assay for NGAL and for concentrations of L-lactic acid., Results: The median concentration of NGAL in vaginal fluid was significantly higher in control women (561 pg/mL) than in women with BV (402 pg/mL; P = .0116) and lower in women with VVC (741 pg/mL; P = .0017). Median lactic acid levels were similar in controls (0.11 mmol/L) and women with VVC (0.13 mmol/L) and were lower in women with BV (0.02 mmol/L; P < .0001). The NGAL and lactic acid concentrations were highly correlated (P < .0001)., Conclusion: A decrease in Lactobacilli and/or lactic acid plus the absence of leukocytes results in lower vaginal NGAL levels that might facilitate the growth of bacteria associated with BV., (© The Author(s) 2015.)

The objective of this work was to evaluate the influence of human papillomavirus (HPV) vaccination on peripheral blood mononuclear cell (PBMC) proliferation and cytokine gene transcription. PBMCs isolated after HPV immunization were incubated with HPV vaccine, phytohemagglutinin, or buffer. Cell proliferation was assessed by MTT reduction assay. RNA was extracted from PBMCs, and the relative concentration of cytokine messenger RNA (mRNA) transcripts (IFN-β, IFN-γ, IL-12, TNF-α, IL-6, IL-17, or IL-10) relative to transcription of the β-actin gene was determined by real-time polymerase chain reaction. PBMC proliferation in response to HPV vaccine and PHA were greater than that observed in unstimulated cells (p<0.001). Cytokine mRNAs were upregulated in stimulated PBMC cultures. The median increase in vaccine-stimulated cultures was: IFN-β=334.4-fold; IL-12=46.33-fold; IFN-γ=12.64-fold; IL-6=9.07-fold; IL-17=7.33-fold; IL-10=6.47-fold; and TNF-α=2.36-fold. The IFN-β expression was significantly higher (p<0.05). Proliferative PBMC responses and multiple cytokine gene expression were detected in women who received the HPV vaccine.

Purpose: To evaluate some microbiological aspects of the vaginal flora and the vaginal trophism of women with premature ovarian failure (POF) in use of oral hormone therapy., Methods: A cross-sectional study with 36 women with POF under the age of 40 years using oral hormonal therapy. They were age matched with 36 women with normal gonadal function (control group). The characteristics of the vaginal epithelium were assessed through the hormonal vaginal cytology, vaginal pH measurement and vaginal health index to identify vaginal disturbances. Vaginal microflora was evaluated by the amine test, bacterioscopy (Nugent score) and culture for fungi to identify vaginal abnormal microflora and fungi infections., Results: Despite the fact that there were no statistical significant differences related to the cytological aspects and pH measurements, it was found that the vaginal health index was highly superior in the control group than in the POF group (23.4 ± 1.8 vs 20.8 ± 3.5), p < 0.0001 despite both groups had trophic scores. There were no statistical significance differences regarding to vaginal microflora types and fungi infection., Conclusion: Oral hormone therapy for young women with POF seems to be good enough to reestablish the epithelium cells, vaginal pH and microflora.

Background: Screening for anal cancer using cytology has not been considered in immunocompetent women. The aim of this study was to identify cytological atypia and human papillomavirus (HPV) DNA in intra-anal specimens from human immunodeficiency virus (HIV)-negative women with and without genital HPV lesions., Methods: This study was a cross-sectional analysis of 142 women who were negative for the HIV: 80 with genital lesions that were associated with HPV and 62 without HPV-induced lesions. The women were evaluated at the Federal University of Ceará from October 2011 to June 2012. The statistical analysis included the Fisher exact test and the odds ratio (CI 95%)., Results: Atypical anal cytology was observed in 24 (29.3%) patients in the study group and in 11 (17.8%) patients in the control group. In cases with at least two sites of HPV-associated lesions, 12 (41.4%) presented atypical cytology (P = 0.0220; OR = 2.7621, 1.1579-6.5889). When the practice of anal sex was evaluated, atypical cytology was observed in 22/43 (34%) [P = 0.0214; OR = 2.519, 1.146-5.534]. HPV DNA was detected in 17/27 (63%) cases with at least two sites of lesions (P = 0.0293, OR = 2.4855, 1.0960-5.6367). In the 33 cases who presented positive HPV DNA test results, the liquid-based cytology results were atypical (P = 0.0212, OR = 2.8, 1.1665-6.7208)., Conclusion: Based on the results, liquid-based cytology may be used to detect intra-anal lesions, especially among women who have a history of anal intercourse or who have genital HPV-associated lesions at multiple sites., (© 2014 Wiley Periodicals, Inc.)