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Objective: To assess the effect of structured counselling on women's contraceptive decisions and to evaluate gynaecologists' perceptions of comprehensive contraceptive counselling.Methods: Belgian women (18-40 years old) who were considering using a combined hormonal contraceptive (CHC) were counselled by their gynaecologists about available CHCs (combined oral contraceptive [COC], transdermal patch, vaginal ring), using a comprehensive leaflet. Patients and gynaecologists completed questionnaires that gathered information on the woman's pre- and post-counselling contraceptive choice, her perceptions, and the reasons behind her post-counselling decision.Results: The gynaecologists (N=121) enrolled 1801 eligible women. Nearly all women (94%) were able to choose a method after counselling (53%, 5%, and 27% chose the COC, the patch, and the ring, respectively). Counselling made many women (39%) select a different method: patch use increased from 3% to 5% (p<0.0001); ring use tripled (from 9% to 27%, p<0.0001). Women who were undecided before counselling most often opted for the method their gynaecologist recommended, irrespective of counselling.Conclusion: Counselling allows most women to select a contraceptive method; a sizeable proportion of them decide on a method different from the one they initially had in mind. Gynaecologists? preferences influenced the contraceptive choices of women who were initially undecided regarding the method to use. [ABSTRACT FROM AUTHOR]

Accessing vaginal pH is fundamental during gynaecological visit for the detection of abnormal vaginal flora (AVF), but use of pH strips may be time-consuming and difficult to interpret. The aim of this study was to evaluate the VS-SENSE test (Common Sense Ltd, Caesarea, Israel) as a tool for the diagnosis of AVF and its correlation with abnormal pH and bacterial vaginosis (BV). The study population consisted of 45 women with vaginal pH ≥ 4.5 and 45 women with normal pH. Vaginal samples were evaluated by VS-SENSE test, microscopy and microbiologic cultures. Comparing with pH strips results, VS-SENSE test specificity was 97.8% and sensitivity of 91%. All severe cases of BV and aerobic vaginitis (AV) were detected by the test. Only one case with normal pH had an unclear result. Concluding, VS-SENSE test is easy to perform, and it correlates with increased pH, AVF, and the severe cases of BV and AV. [ABSTRACT FROM AUTHOR]

Background: It is commonly stated that Candida in the vagina prefers a low pH to develop infection. However, mixed infections of Candida with bacterial vaginosis (BV) and aerobic vaginitis (AV) are rather common and may challenge the rule that Candida should only be looked for in low vaginal pH settings. In this study we tested whether the vaginal pH in acute vaginal candidosis is lower than in women successfully treated to prevent Candida recurrences., Methods: Vaginal pH and microscopy findings of vaginal microbiota were recorded during 12 visits over 1.5 years in 117 patients medically monitored during a degressive fluconazole maintenance regimen for proven recurrent vulvovaginal candidosis (ReCiDiF trial). The fluctuation of the mean pH of and microscopic findings of the vaginal smears were studied before, during and after the treatment., Results: The mean vaginal pH of women with acute infection before or after ending maintenance treatment was (4.7±0.8 and 4.8 ±1.0, respectively, p>0.05). During maintenance treatment with fluconazole, the pH dropped significantly to 4.5±0.8 (p=0.01). Depression of Lactobacilli spp. (increased lactobacillary grades) was more frequent during the acute, pre-treatment period (30.0%) than during the treatment period (23.1%, p=0.03). Aerobic vaginitis type flora was also more prevalent pre-treatment than during treatment (30.0% vs 22.2%, OR=0.7 (95%CI 0.5-0.9), p=0.01)., Discussion: In women with RVVC, acute vaginal Candida infection is associated with an increased pH, and disturbed vaginal bacterial microbiota. During fluconazole maintenance treatment, the pH drops to normal levels and the lactobacillary grade improves., Condensation: Acute Candida vulvovaginitis can be associated with a disturbance of the vaginal microbiota. In patients with recurrent vulvovaginal candidosis, decrease of pH, and increase of Lactobacilli spp. were observed during fluconazole maintenance treatment. This pH drop was seen in all response groups. This contradicts the common belief that active vaginal Candida infection is related to low pH., (Copyright © 2020. Published by Elsevier Inc.)

In the last years, the use of probiotics, including Lactobacillus species, has received much attention to prevent and treat vaginal disorders. These species have been described as having the ability to colonize the epithelial surface and produce antimicrobial metabolites that are able to control the remaining vaginal microflora. This study aimed to identify and characterize, for the first time, a bacteriocin natively produced by Lactobacillus acidophilus KS400 (probiotic strain from Gynoflor ® -Medinova AG, Switzerland) and its antimicrobial activity against relevant urogenital pathogens. After organic acids and hydrogen peroxide neutralization in the fermented Lactobacillus acidophilus KS400 culture medium, bacteriocin activity was tested against the indicator microorganism Lactobacillus delbrueckii ATCC9649. The fermentation of Lactobacillus acidophilus KS400 for bacteriocin production was carried out in batch mode, and its antimicrobial activity, optical density and pH were monitored. After production and extraction, the bacteriocin molecular weight was estimated by electrophoresis and tested against vaginal pathogenic microorganisms. As described for other bacteriocins, batch fermentation profiles indicated that bacteriocin production occurs during the exponential growth phase of the lactobacilli, and declines during their stationary growth phase. The molecular weight of the bacteriocin is approximately 7.5 kDa. The bacteriocin containing protein extract was shown to inhibit the growth of Gardnerella vaginalis, Streptococcus agalactiae, Pseudomonas aeruginosa and the indicator strain Lactobacillus delbrueckii ATCC9649. We conclude that L. acidophilus KS400 produces bacteriocin with antimicrobial activity against relevant urogenital pathogens.

Purpose: Cervicovaginal Atopobium vaginae and Gardnerella vaginalis are strongly associated with bacterial vaginosis (BV) and are the main components of vaginal biofilms. The low efficacy of BV treatment with metronidazole may be due to the presence of such biofilms. Thus, the aim of this study was to compare the pretreatment cervicovaginal loads of A. vaginae and G. vaginalis for women who restored normal flora and those who persisted with BV after a full course of oral metronidazole., Methodology: In this cross-sectional study, 309 reproductive-aged women were recruited in a primary health care service in Botucatu, Brazil. Cervicovaginal samples were tested for genital tract infections, microscopic classification of local microbiota and molecular quantification of A. vaginae and G. vaginalis., Results: All the participants with concurrent cervicovaginal infections (n=64) were excluded. A total of 84 out of 245 (34.3 %) women had BV at enrolment and 43 (51.2 %) of them completed the treatment and returned for follow-up. Evaluation of the vaginal microbiota at follow-up showed that 29 (67.4 %) women restored normal vaginal flora, while 14 (32.6 %) still had BV. The pretreatment loads of G. vaginalis were lower in women with treatment failure (P=0.001) compared to those who successfully restored normal flora. The loads of A. vaginae did not differ between the groups., Conclusion: Although G. vaginalis produces several virulence factors and its loads correlate positively with those of A. vaginae, higher cervicovaginal quantities of these bacteria are not associated with treatment failure of BV after oral metronidazole.

Although being an utterly frequent, non-mortal, yet distressing disease, and despite good knowledge of the pathogenesis and the availability of specific and safe treatment, vulvovaginal Candida (VVC) infection remains one of the most enigmatic problems for both physicians and patients. Good treatment requires a proper diagnosis. Too many caregivers (and patients treating themselves) react too simple-minded on the symptoms of VVC and treat VVC where they see it on the vulva. In this opinion paper, we plea for a thorough examination of women with VVC, especially in those women who suffer from recurrent disease since a long time, sometimes decades, which necessitates intensive examination of the vaginal flora, as this is invariably the reservoir for relapses and recurrent vulvitis. Examination of such complicated cases requires experienced clinical judgement, expertise bedside phase contrast microscopy of fresh vaginal fluid, classical cultures on Sabouroud medium and, if still unresolved, repetitive cultures taken by the patient herself at moments of symptoms, and/or nuclear acid amplification techniques to detect Candida genes in the vaginal fluid. Even if only vulvitis is evident, thorough expert examination of vaginal fluid is obligatory to diagnose VVC., (© 2016 Blackwell Verlag GmbH.)

Abnormal vaginal flora (AVF), indicative of bacterial vaginosis (BV) and/or aerobic vaginitis (AV), amongst other abnormalities, is a risk factor for multiple complications in pregnant as well as non-pregnant women. Screening for such conditions could help prevent these complications. Can self-testing for increased vaginal pH reliably detect BV and other high-risk microflora types, and is this more accurate than performing Gram stain-based Nugent score when screening for high-risk microflora? A total of 344 women presenting at different outpatient clinics in Mulago Hospital and Mbuikwe Outpatient clinics in Kampala, Uganda, were asked to test themselves by introducing a gloved finger into the vagina and smearing it on a microscopy slide, on which a pH strip was attached. Self-assessed categories of normal (pH 3.6-4.4), intermediate (4.5-4.7) or high pH (>4.7) were compared with demographic and with centralised microscopic data, both in air-dried rehydrated wet mounts (Femicare), as well as in Gram-stained specimens (Nugent). AVF was present in 38 %, BV in 25 % and AV in 11 % of patients. High pH and AVF is correlated with human immunodeficiency virus (HIV), infertility, frequent sex, but not vaginal douching. Screening for raised pH detects 90 % of AVF cases, but would require testing over half of the population. As AV and non-infectious conditions are frequent in women with AVF and high pH, Nugent score alone is an insufficient technique to screen women for a high-risk vaginal microflora, especially in infertile and HIV-infected women.

Purpose: To evaluate a real-time PCR-based technique to quantify bacteria associated with aerobic vaginitis (AV) as a potential test., Methods: Vaginal samples from 100 women were tested by wet-mount microscopy, gram stain and quantitative real-time PCR targeting Enterobacteriacea, Staphylococcus spp., Streptococcus spp., Enterococcus spp., Escherichia coli, Streptococcus agalactiae, S. aureus; Lactobacillus spp. AV diagnosis obtained by wet-mount microscopy was used as reference., Results: Some level of AV was diagnosed in 23 (23.7 %) cases. Various concentrations of Enterobacteriacea, Staphylococcus spp., Streptococcus spp. were detected an all patients. Enterococcus spp. were detected in 76 (78.3 %) cases. Summarized concentrations of aerobes were tenfold higher in AV-positive compared to AV-negative cases [7.30lg vs 6.06lg (p = 0.02)]. Concentrations of aerobes in severe, moderate and light AV cases did not vary significantly (p = 0.14). Concentration of lactobacilli was 1000-fold lower in AV-positive cases compared to normal cases (5.3lg vs 8.3lg, p < 0.0001). Streptococcus spp. dominated in the majority of AV-positive cases [19/22 (86.4 %) samples]. The relation of high loads of aerobes to the low numbers of Lactobacilli are a reliable marker for the presence of AV and could substitute microscopy as a test., Conclusions: PCR may be a good standardized substitution for AV diagnosis in settings where well-trained microscopists are lacking.

Objective: Is self-assessed vaginal pH measurement to detect abnormal vaginal bacterial microflora (AVF) an adequate prescreening method for detection of genital sexually transmitted infections (STIs)?, Materials and Methods: A total of 360 Ugandan women tested themselves with a gloved finger and a pH color strip. PCR for bacterial vaginosis (BV)-associated bacteria was tested by PCR for Mycoplasma hominis, Ureaplasma urealyticum, and/or Atopobium vaginae, while the STIs were diagnosed by positive PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and/or Trichomonas vaginalis., Results: A strong correlation was found between self-assessed pH values and BV-associated bacteria (P<0.0001), but not with STIs, not as single infections, nor in general., Conclusion: Self-measured vaginal pH correlated well with markers of high-risk microflora types such as BV or aerobic vaginitis, but not with STIs. Hence, in a screening program addressing AVF in low-resource countries, extra specific tests are required to exclude STIs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and immunogenicity of an investigational trivalent group B streptococcal vaccine in pregnant women and antibody transfer to their newborns., Methods: The primary outcome of this observer-blind, randomized study was to estimate placental antibody transfer rates at birth. Secondary outcomes included measurement of serotype-specific antibodies at screening, 30 days postvaccination, at delivery, and 91 days postpartum, infant antibody levels at 3 months of age, the potential effect on routine infant diphtheria vaccination at 1 month after the third infant series dose, and safety in mother and infant participants through at least 5 months postpartum. Sample size was based on 60 participants in the vaccine group giving a probability of observing at least one adverse event of 90% if the actual rate of the event was 3.8%., Results: From September 2011 to October 2013, 86 pregnant women were allocated in a 3:2 ratio to receive an investigational group B streptococcal vaccine containing glycoconjugates of serotypes Ia, Ib, and III or placebo. Demographics were similar across groups. Transfer ratios were 66-79% and maternal geometric mean concentrations increased 16-, 23-, and 20-fold by delivery against serotypes Ia, Ib, and III, respectively, Women with no detectable antibodies at inclusion had lower responses than those with detectable antibodies. Three months after birth, infant antibody concentrations were 22-25% of birth levels. Antidiphtheria geometric mean concentrations were similar across groups. In the vaccine and placebo groups, 32 of 51 women (63%) and 26 of 35 women (74%) reported adverse effects, respectively., Conclusion: The investigational vaccine was well-tolerated without safety signals in recipients and their infants or interference with routine infant diphtheria vaccination, although further studies on safety and effectiveness are needed. The investigational vaccine was immunogenic for all serotypes, particularly among women with detectable antibody levels at baseline. Antibody transfer to neonates was at similar levels to other maternally administered polysaccharide vaccines., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01446289.

Aerobic vaginitis (AV) is a vaginal infectious condition which is often confused with bacterial vaginosis (BV) or with the intermediate microflora as diagnosed by Nugent's method to detect BV on Gram-stained specimens. However, although both conditions reflect a state of lactobacillary disruption in the vagina, leading to an increase in pH, BV and AV differ profoundly. While BV is a noninflammatory condition composed of a multiplex array of different anaerobic bacteria in high quantities, AV is rather sparely populated by one or two enteric commensal flora bacteria, like Streptococcus agalactiae, Staphylocuccus aureus, or Escherichia coli. AV is typically marked by either an increased inflammatory response or by prominent signs of epithelial atrophy or both. The latter condition, if severe, is also called desquamative inflammatory vaginitis. As AV is per exclusionem diagnosed by wet mount microscopy, it is a mistake to treat just vaginal culture results. Vaginal cultures only serve as follow-up data in clinical research projects and are at most used in clinical practice to confirm the diagnosis or exclude Candida infection. AV requires treatment based on microscopy findings and a combined local treatment with any of the following which may yield the best results: antibiotic (infectious component), steroids (inflammatory component), and/or estrogen (atrophy component). In cases with Candida present on microscopy or culture, antifungals must be tried first in order to see if other treatment is still needed. Vaginal rinsing with povidone iodine can provide rapid relief of symptoms but does not provide long-term reduction of bacterial loads. Local antibiotics most suitable are preferably non-absorbed and broad spectrum, especially those covering enteric gram-positive and gram-negative aerobes, like kanamycin. To achieve rapid and short-term improvement of severe symptoms, oral therapy with amoxyclav or moxifloxacin can be used, especially in deep dermal vulvitis and colpitis infections with group B streptococci or (methicillin resistant) Staphylococcus aureus. Since the latter colonizations are frequent, but seldom inflammatory infections, we in general discourage the use of oral antibiotics in women with AV. In cases with a severe atrophy component (more than 10 % of epithelial cells are of the parabasal type), local estrogens can be used; and in postmenopausal or breast cancer patients with a contraindication for estrogens, even a combination of probiotics with an ultra-low dose of local estriol may be considered.

Objective: The aim of the study was to evaluate the diagnostic value of Nugent score, wet mount microscopy, and polymerase chain reaction (PCR) test developed in Russia for bacterial vaginosis (BV) diagnosis., Materials and Methods: One hundred Caucasian women were enrolled in this study. Three vaginal samples were taken from each participant: 1 for PCR analysis, 1 for Nugent score evaluation, and 1 for wet mount microscopy. The smears for microscopy were air-dried and sent to Femicare, Tienen, Belgium, for blinded analysis by microscopy. Multiplex real-time PCR was performed using primers and probes targeting Gardnerella vaginalis, Atopobium vaginae, Lactobacillus species, and total quantity of bacterial DNA (16SrRNA gene)., Results: Agreement among the 3 methods was 72 (73.5%) of 98 samples. Agreement between Nugent score and PCR results was 77 (78.6%) of 98 samples; between wet mount microscopy and PCR, 81 (82.65%) of 98 samples; between wet mount microscopy and Nugent score, 84 (85.7%) of 98 samples. The sensitivity and specificity of the methods studied were as follows: 75% (21/28) and 97.1% (68/70) for Nugent score, 96.4% (27/28) and 94.3% (66/70) for wet mount microscopy, 92.8% (26/28) and 85.7% (60/70) for PCR, respectively., Conclusions: This study demonstrated that wet mount microscopy is a superior method for BV diagnosis. The PCR test under study showed a high sensitivity and can be used for discrimination between normal flora and BV.

Objective: Is it feasible to learn the basics of wet mount microscopy of vaginal fluid in 10 hours?, Materials and Methods: This is a pilot project wherein 6 students with different grades of education were invited for being tested on their ability to read wet mount microscopic slides before and after 10 hours of hands-on training. Microscopy was performed according to a standard protocol (Femicare, Tienen, Belgium). Before and after training, all students had to evaluate a different set of 50 digital slides. Different diagnoses and microscopic patterns had to be scored. κ indices were calculated compared with the expert reading., Results: All readers improved their mean scores significantly, especially for the most important types of altered flora (p < .0001). The mean increase in reading concordance (κ from 0.64 to 0.75) of 1 student with a solid previous experience with microscopy did not reach statistical significance, but the remaining 5 students all improved their scores from poor performance (all κ < 0.20) to moderate (κ = 0.53, n = 1) to good (κ > 0.61, n = 4) concordance. Reading quality improved and reached fair to good concordance on all microscopic items studied, except for the detection of parabasal cells and cytolytic flora., Conclusions: Although further improvement is still possible, a short training course of 10 hours enables vast improvement on wet mount microscopy accuracy and results in fair to good concordance of the most important variables of the vaginal flora compared to a reference reader.

Objective: The purpose of this study was to assess the cervicovaginal levels of proinflammatory cytokines in women with Chlamydia trachomatis (CT) infection in the presence of bacterial vaginosis (BV) and normal flora and to compare with those negative for CT., Materials and Methods: In this cross-sectional study, nonpregnant women were enrolled at 2 outpatient clinics and at 1 primary medical care unit in São Paulo State, Brazil. Cervicovaginal samples from 256 women with BV, of which 68 (26.6%) had concomitant CT infection and 188 (73.4%) were CT-negative, were measured for interleukin-1β (IL-1β), IL-6, and IL-8 by enzyme-linked immunosorbent assay. A matching number of samples from women with normal flora, CT-positive (n = 68) and negative (n = 188), were evaluated as control. Cytokine levels were compared by Mann-Whitney test and differences were considered significant at p < .05., Results: In CT-negative women, IL-1β was increased in BV (p < .001) when compared to normal flora, while the levels of IL-6 and IL8 were unchanged. The presence of CT infection was not associated with differences on cytokine levels in women with normal flora. However, women with BV had higher levels of IL-1β (p = .02), IL-6 (p = .02), and IL-8 (p = .03) in the presence of CT when compared to those who tested negative for CT., Conclusions: Detection of endocervical CT is associated with increased cervicovaginal IL-1β, IL-6, and IL-8 levels in women with concomitant BV but not in those with normal flora.

Introduction: The disturbing, foul-smelling discharge of bacterial vaginosis (BV) is a nuisance to women. Treatment possibilities for BV are limited and only achieve complete cure in 65 to 85% of cases. In most women, the condition relapses within weeks to months after treatment., Areas Covered: In search of new therapeutic actions to cure, prevent or delay recurrences of BV, PubMed and web of science were searched for papers with i) decent study layout, ii) proper statistics, iii) comparison group (placebo or standard treatment) and iv) language English, French, Dutch or German. The following keywords were used: bacterial vaginosis and treatment or management or therapy or prophylaxis or prevention. Results were grouped in treatment categories and were discussed., Expert Opinion: Clindamycin and metronidazole are the standard drugs for BV. As other antibiotic and acidifying treatments are progressively being studied, like tinidazole, rifaximin, nitrofuran, dequalinium chloride, vitamin C and lactic acid, more options have become available for switching therapy, combining therapies and long-term prophylactic use to prevent recurrences. Further studies are needed. Also, adjuvant therapy with probiotics may have a significant role in improving efficacy and in preventing recurrences. However, it is unlikely that probiotics will replace antibiotherapy.

Objective: To determine whether von Frey filaments are effective in the standardized assessment of the severity of focal provoked vulvodynia (FPV) syndrome., Study Design: The data of 30 women with FPV attending monthly at our vulvovaginal disease clinic, for a collective total of 141 visits over 6 months, were analyzed. At each visit sensitivity tests at the vulvar vestibule were performed at the 5 and 7 o'clock area, totaling 282 measurements. A questionnaire, blinded to the examining physician, and a visual analogue score (VAS) of pain ranging from 1 (no pain) to 10 (maximal pain) was obtained of the discomfort felt when attempting sexual intercourse., Results: The VAS, the investigator assessment of redness, and the 1 to 10 score result of the cotton swab touch test at 5 and 7 o'clock were superior diagnostic tools for assessing the severity of the pain when compared to the use of von Frey filaments., Conclusion: Although elegant because of the promise of objective, semiquantitative measurements, von Frey filaments are less suitable devices to assess severity of disease and response to treatment than are cotton swab 1 to 10 pain scores and clinical parameters like subjective pain (VAS) and objective focal redness.

Objective: Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?, Design: Cross sectional study., Setting: Screening healthy Belgian women with low infection risk., Sample: 63,251 consecutive liquid based cervical samples., Methods: Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities., Main Outcome Measures: Association of TV and HPV with cervix dysplasia., Results: The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL., Conclusions: We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.

Objective: To evaluate levels of proinflammatory cytokines and sialidase activity in aerobic vaginitis (AV) in relation to normal vaginal flora and bacterial vaginosis (BV)., Study Design: In this cross-sectional study, a total of 682 consecutive non-pregnant women attending the gynecology service were assessed and 408 women were included. Vaginal rinsing samples were collected from 223 women with microscopic finding of BV (n=98), aerobic vaginitis (n=25) and normal flora (n=100). Samples were tested for interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and sialidase activity., Results: Compared to women with normal flora, vaginal levels of IL-1β were highly increased in both BV and AV (p<0.0001). Significantly higher vaginal IL-6 was detected in AV (p<0.0001) but not in BV, in relation to normal flora. Women with AV also presented increased IL-8 levels (p<0.001), while those with BV presented levels similar to normal flora. Sialidase was increased in BV and AV compared with the normal group (p<0.0001) but no difference in sialidase activity was observed between BV and AV., Conclusion: A more intense inflammatory host response occurs for AV than for BV when compared with normal flora. Furthermore, the increased sialidase activity in AV and BV indicates that both abnormal vaginal flora types can be harmful to the maintenance of a healthy vaginal environment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We estimated type-specific prevalence of human papillomavirus (HPV) and examined risk factors for abnormal cervical cytology among 296 female sex workers from Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1 sero-positivity was associated with high-grade cervical lesions, particularly among women with CD4 count less than 500 cells/mm(3) (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 1.7-24.9). Among women who had normal cytology at the time of entry into the study, the risk of having an abnormal Pap smear within one year was significantly elevated for women with multiple HPV types at study entry (adjusted odds ratio [aOR] = 6.0; 95% CI: 2.3-15.7) and with a subset of HR HPV types (aOR = 4.2; 95% CI: 1.6-11.2). Detection of multiple concurrent HPV infections may be a useful marker to identify women at risk of developing precancerous lesions in populations of high HPV prevalence.

Objectives: To investigate if the participation of Atopobium vaginae, Megasphaera sp. and Leptotrichia sp. in the bacterial community of bacterial vaginosis (BV) is associated with distinct patterns of this condition., Methods: In this cross-sectional controlled study, 205 women with BV and 205 women with normal flora were included. Vaginal rinsing samples were obtained for measuring the levels of pro-inflammatory cytokines and bacterial sialidases. Real-time PCR was used to quantify the BV-associated bacteria and to estimate the total bacterial load using the 16S rRNA. Principal component analysis (PCA) using the measured parameters was performed to compare the BV samples with lower and higher loads of the species of interest., Results: Higher bacterial load (p<0.001), levels of interleukin 1-β (p<0.001) and sialidase activity (p<0.001) were associated with BV. Women with BV and higher relative loads of A vaginae, Megasphaera sp. and Leptotrichia sp. presented increased sialidase activity, but unchanged cytokine levels. PCA analysis did not indicate a different pattern of BV according to the loads of A vaginae, Megasphaera sp. and Leptotrichia sp., Conclusions: Greater participation of A vaginae, Megasphaera sp. and Leptotrichia sp. in vaginal bacterial community did not indicate a less severe form of BV; moreover, it was associated with increased sialidase activity.

Objective: To compare efficacy and tolerability between different regimens of rifaximin vaginal tablets and a placebo for treatment of bacterial vaginosis., Methods: In a prospective study carried out at 13 sites in 3 European countries between August 2009 and October 2010, White, non-pregnant, premenopausal women with bacterial vaginosis were randomly assigned to receive rifaximin at 100mg for 5 days (100mg/5 days), 25mg/5 days, or 100mg/2 days, or placebo. Women were assessed at 7-10 and 28-35 days. Diagnosis and cure were based on Amsel criteria and Nugent score. Fisher exact test was used to compare cure rates., Results: Among 114 women recruited, 103 were evaluable for drug efficacy. Therapeutic cure rate at first follow-up was higher in the rifaximin 25mg/5 days (48%, P=0.04), 100mg/2 days (36.0%), and 100mg/5 days (25.9%) groups than in the placebo group (19.0%). At second follow-up, therapeutic cure rate was 28.0%, 14.8%, and 4.0% in the respective groups versus 7.7% in the placebo group. No difference in adverse events was observed., Conclusion: Rifaximin at 25mg/5 days showed better therapeutic cure rates and maintenance of therapeutic cure after 1 month versus placebo. All treatment regimens were well tolerated. EudraCT number: 2009-011826-32., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

The application of high-throughput sequencing methods has raised doubt in the concept of the uniform healthy vaginal microbiota consisting predominantly of lactobacilli by revealing the existence of more variable bacterial community composition. As this needs to be analyzed more extensively and there is little straightforward data regarding the vaginal mycobiome of asymptomatic women we aimed to define bacterial and fungal communities in vaginal samples from 494 asymptomatic, reproductive-age Estonian women. The composition of the vaginal microbiota was determined by amplifying bacterial 16S rRNA and fungal internal transcribed spacer-1 (ITS-1) regions and subsequently sequencing them using 454 Life Sciences pyrosequencing. We delineated five major bacterial community groups with distinctive diversity and species composition. Lactobacilli were among the most abundant bacteria in all groups, but also members of genus Gardnerella had high relative abundance in some of the groups. Microbial diversity increased with higher vaginal pH values, and was also higher when a malodorous discharge was present, indicating that some of the women who consider themselves healthy may potentially have asymptomatic bacterial vaginosis (BV). Our study is the first of its kind to analyze the mycobiome that colonizes the healthy vaginal environment using barcoded pyrosequencing technology. We observed 196 fungal operational taxonomic units (OTUs), including 16 OTUs of Candida spp., which is more diverse than previously recognized. However, assessing true fungal diversity was complicated because of the problems regarding the possible air-borne contamination and bioinformatics used for identification of fungal taxons as significant proportion of fungal sequences were assigned to unspecified OTUs.

Objective: Is treatment of provoked localized vulvodynia with cutaneous lysate skin cream containing human cytokines effective?, Methods: This is a double-blind placebo-controlled randomized crossover trial with a study and a placebo cream applied twice daily for 3 months, 1-week washout, followed by a 3-month crossover medication in 30 patients experiencing provoked localized vulvodynia with visible vulvar erythema. Tolerability of the product, sexual functioning, and clinical findings were the main outcomes. A linear model for repeated measures was used for all visits. Effect after 4 weeks of treatment, effect after 12 weeks of treatment, and, finally, carryover effects of first and second order were estimated. A Wilcoxon signed rank test was used to evaluate 4- and 12-week changes within a group, and Mann-Whitney U test was used to evaluate 4- and 12-week changes between groups., Results: Tolerability of the cream was excellent and not different from that of placebo. During the first 12 weeks, use of the active cream resulted in a significant reduction in pain during sexual activity after 4 and 12 weeks (p < .05); however, use of the placebo cream did not. When analyzing the entire pain data with the statistical model for crossover clinical study design, the active cream resulted in a decrease of 1.1 points (95% confidence interval = -0.6 to 2.8, p = .20) and 1.3 points (95% confidence interval = 0.1 to 2.5, p = .037) in the visual analog scale score compared with that of placebo after 4 and 12 weeks of treatment, respectively. There was evidence for a second-order carryover effect (p = .024). The pain reduction was most evident for women with secondary dyspareunia. Erythema was reduced after use of the cream at 4 (p = .03) and 12 (p = .01) weeks but not after placebo., Conclusions: As opposed to placebo, use of cutaneous lysate cream was more effective in reducing focal redness and pain while having intercourse in patients with provoked localized vulvodynia with erythema.

Objective: The purpose of this study was to test the correlation of the amount of Atopobium vaginae with the most commonly used markers for bacterial vaginosis (BV)., Materials and Methods: We enrolled 103 nonpregnant and premenopausal women that were positive for BV by Amsel criteria and with a Nugent score higher than 3. All women were negative for yeast, Chlamydia trachomatis, Trichomonas vaginalis, and Neisseria gonorrhoeae. A. vaginae concentration was determined by quantitative polymerase chain reaction from samples of vaginal rinsings with 2 mL of sterile saline., Results: There was no difference in the median values of A. vaginae concentration when comparing samples with presence or absence of each individual Amsel criterion. In the case of a higher pH cutoff value of 4.9, greater amounts of this microorganism (p = .02) were found. In addition, correlation tests showed that A. vaginae concentration is positively correlated with pH (p < .001) and with Nugent scores (p = .003)., Conclusions: The quantification of A. vaginae is useful for identification of the most severe cases of BV.

Objectives: The purpose of this study was to determine whether a low splenic artery pulsatility index (PI) and reduced flow through the left portal vein are involved in redistribution of fetal growth restriction., Methods: Forty-two women with prenatally diagnosed intrauterine growth restriction of singleton fetuses were included. The next pregnant woman with an appropriately growing fetus, matched for gestational age, was selected as a control. Blood flow velocities were measured in the splenic artery and left portal vein. Obstetric and perinatal information was obtained from standardized medical records., Results: The blood flow through the left portal vein was significantly reduced compared with the controls (P < .0001). Placental impairment in fetal growth restriction was clearly linked to a decreased splenic artery PI (P = .0004). In growth-restricted fetuses with reduced left portal vein flow and a splenic artery PI below the 5th percentile, perinatal mortality, a low 5-minute Apgar score, and neonatal metabolic acidosis were observed significantly more often (P = .04, .01, and .004; P = .03, .03, and .006, respectively)., Conclusions: Reduced blood flow through the left portal vein and low resistance in the splenic artery can be found in growth-restricted fetuses with adverse neonatal outcomes.

We assessed the acceptance of self-testing for vaginal pH in 344 Ugandan women in different clinical settings. Women tested themselves by insertion of a gloved finger into the vagina to test vaginal pH and provide a smear on a glass slide. None of the tested women found the test very difficult: 8% found it somewhat difficult, 16% rather easy and 76% very easy to do. Of the 20% who found it difficult to read the test result, more women were attending a family planning clinic or had a higher diploma (P = 0.001). Pregnant women were least likely to understand of the meaning of the test, while those visiting family planning clinics had the opposite experience. HIV-infected women were most motivated to accept: 95% would be happy to use the test more often if requested, and another 3.5% felt they might be better motivated to do repeat testing after extra explanation. Self-sampling of vaginal pH is well accepted by Ugandan women. Our new method also allows diagnostic work-up by formal microscopy. Before commencing large-scale population screening, unexpected reactions of different subpopulations should be taken into account.

Purpose: The purpose of the study was to find an association between the uterine and umbilical arteries blood flow patterns in growth-restricted (FGR) and normal fetuses and placental microscopic lesions., Methods: Fifty women with prenatally suspected and post-delivery confirmed FGR of singleton fetuses were enrolled in a case-controlled follow-up study from May 2007 to December 2008. Unselected patients with appropriately growing fetuses, matched for gestational age, served as controls. Uterine and umbilical Doppler waveforms were recorded before delivery., Results: Compared with control group with normal Doppler, FGR women with abnormal Doppler velocimetry of uterine and umbilical arteries had more intervillous thrombi (p = 0.01 and p < 0.0001, respectively) and villous infarctions (p = 0.02 and p = 0.0003, respectively). Thickening of the basal membrane and villitis was clearly linked to the FGR (p = 0.006 and p = 0.01). Vasculitis, on the other hand, is linked to normal growth, without affecting Doppler velocities., Conclusions: Abnormal Doppler may predict hemorrhagic and ischemic placental lesions in FGR pregnancies and may lead to future improvement of the management of current and subsequent pregnancies.

Objectives: Analysis of characteristics of patients with introital central dyspareunia. Is late coitarche (age at first sexual intercourse) a risk factor for introital dyspareunia?, Study Design: 145 women attending a vulvo-vaginitis clinic in secondary and tertiary care center in Tienen and Leuven, Belgium, with central introital pain during sexual intercourse., Results: The mean age of the study group was 32 years, and 5% were 60 years of age or older. Of the patients, 51% had primary and 49% secondary dyspareunia. Before referral, two-thirds of the patients had already tried several types of therapy, including psychiatric help in 16% of cases. The study group of patients with central introital dyspareunia had a coitarche at a mean of 18.3 years. 72% of the dyspareunic women with coitarche later than 18 had to regularly interrupt intercourse because of pain, compared with 52% of women with coitarche before 18 (p<0.05). A strong correlation was found between the age of sexual debut and the necessity to interrupt intercourse attempts due to pain (p<0.001). Frequency of intercourse was also found to be inversely related to coitarche., Conclusion: Women with introital dyspareunia had their sexual debut at a later age than otherwise comparable women. Late coitarche is inversely related to frequency of attempted intercourse and to the necessity to interrupt intercourse due to pain, suggesting a relation between coitarchal age and severity of dyspareunia. A possible explanation is increased fibrosis and stiffening of the hymenal remnants at the posterior vulvar commissural due to increasing age in primary, and repeated injury by sexual contacts in secondary, central introital dyspareunia patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Problem: We compared the frequency of intra-amniotic infection in preterm labor (PL) with women not in labor, and correlated infection with amniotic fluid (AF) cytokines. Detailed identification of species, especially mycoplasmata, was tried to improve our understanding of the pathogenesis of PL., Method of Study: AF from 20 women with PL and 20 controls were evaluated. Infection was detected by PCR for Mycoplasma hominis, Ureaplasma urealyticum and 16S rRNA bacterial gene, which was cloned and sequenced for bacterial identification. Interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α levels were measured by ELISA., Results: Frequency of intra-amniotic infection is higher in PL (40.0%). Sequencing-based method identified Bacteroides fragilis, Prevotella bivia and Leptotrichia amnionii, in addition to Mycoplasma species detected by PCR. AF infection correlated with increased IL-1β and IL-6 levels., Conclusion: The frequency of intra-amniotic infection, especially M. hominis, in PL women who delivered with 7 days, is high and correlates with high IL-1β and IL-6 levels, but not IL-8., (© 2011 John Wiley & Sons A/S.)

Background: The levonorgestrel intrauterine system (LNG-IUS) combines a uterine foreign body and the continuous release of low-dose levonorgestrel for contraception. Its influence on the rate of vulvovaginal infections and flora disturbance is insufficiently known, but important for contraceptive advice in women, especially those who develop recurrent vaginosis or Candida vulvovaginitis., Study Design: Slides of 286 women who had a Pap smear taken before and 1 to 2 years after placement of a LNG-IUS were blindly reviewed for the presence of abnormal vaginal flora (AVF), bacterial vaginosis (BV), aerobic vaginitis (AV) and Candida vaginitis (CV)., Results: Prior to insertion, there were no differences in vaginal flora abnormalities between women using different kinds of contraception. LNG-IUS users did not have different rates of AVF, BV, AV or CV, but the general risk to develop any infection was increased. Uterine bleeding after insertion did not seem to predict a different flora type., Conclusion: We found that Pap smears suggested more vaginal infections after 1 year of LNG-IUS use than prior to insertion of the device., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR., Study Design: Between May 2007 and December 2008 we performed detailed macroscopic and histological examination of singleton placentas of 50 consecutive neonates with fetal growth restriction (FGR group) and compared them to 50 normal fetuses, born next to an FGR case, as a control group., Results: Gestational age, birth weight, spontaneous delivery rate, mean weight of the placenta and the fetal-placental weight ratio were all lower in the FGR group than in the control group (p<0.05). Thickening of the villous trophoblastic basal membrane, incidence of villous infarction, presence of thrombi or haematomas and the incidence of villitis were more common in the FGR group than in the controls (p<0.05). There were, however, no significant differences in perivillous fibrin deposition, stromal fibrosis and cytotrophoblast proliferation between the groups. In FGR women who smoked, intervillous haematomas and villous infarction were more common (p<0.05) than in controls., Conclusions: All macroscopic and microscopic pathological changes associated with FGR were directly linked to reduction of placental blood flow. As smoking is a main risk factor for these placental abnormalities these results emphasize the need to persuade women to quit smoking not only during pregnancy, but even better long before pregnancy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Women suffering from recurrent vulvo-vaginal candidosis (RVC) often follow medical and non-medical advices to diminish the severity and frequency of the recurrences, but the impact of such interventions is unclear. The aim of this study was to identify differences in life style habits of women with RVC compared with normal women and to define which changes have influenced the frequency of recurrences in these women. Fifty-one women with RVC and 51 age-matched control women without a history of RVC were sent a questionnaire. History of allergic disease (OR 2.8) and use of corticoids (OR 5) were more frequent in patients with RVC than controls. When interrogated about beneficial changes introduced in their life style habits, lowering the intake of sugars, preventing perineum humidity and stopping contraceptive pills were factors offering substantial improvement. Apart from an increased risk of having an allergic constitution, no differences in the medical history or life style habits were evident between women with RVC and healthy women. However, women with RVC have introduced several changes in life style habits that proved beneficial to them. Among these changes, lowering intake of sugars, preventing perineum humidity and stopping oral contraceptives were the most important., (© 2009 Blackwell Verlag GmbH.)

AIM.: To study the relationship between abnormal vaginal flora (AVF) in the first trimester as a risk factor for shortening cervix length (CL) at second and third trimester, and to assess the combination of these factors in predicting preterm delivery. METHODS.: 1026 unselected low risk women seen before 16 weeks of pregnancy underwent sampling of vaginal fluid for wet mount microscopy at a central laboratory blinded to clinical data. Disappearance of lactobacilli and bacterial vaginosis (BV) were scored according to standardized definitions. Specific cultures were performed for M hominis, U urealyticum, aerobic vaginitis (AV) and vaginal colonization with Candida. CL was measured by transvaginal ultrasound at 10-14, 20-24 and at 30-34 weeks, and gestational age at delivery was recorded. RESULTS.: Short cervix (CL below the lower quartile) at 10-14 weeks is related to a lower CL at 20-24 and 30-34 weeks of gestation (p=0.01, p=0.005 respectively). Short cervix at 20-24 weeks, but not at 10-14 weeks, was predictive for preterm birth. In patients with M. hominis and/or with severe AV at 10-14 weeks, the cervix appeared shorter at 20-24 and at 30-34 weeks than in other women. Increased risk for preterm birth in women with a shorter cervix at 10-14 weeks and AVF could not be proved by this study. DISCUSSION.: Presence of AV or M. hominis is associated with a shorter cervix at 20-24 and 30-34 weeks. Although a short cervix at 10-14 weeks increases the likelihood of having a short cervix later in pregnancy, it was not a prerequisite for AVF to be associated with preterm delivery. Therefore, in the pathogenesis of preterm birth, certain types of AVF may be involved directly in the process of cervical shortening, rather than being exposed to the intrauterine cavity more readily by a short cervix in the early stages of pregnancy. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate 'don't do's', unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To evaluate the efficacy of lyophilized lactobacilli in combination with 0.03 mg estriol when compared to metronidazole in the treatment of bacterial vaginal infections., Setting: Multicenter, randomized, single-blind, active-controlled pilot study in 3 independent gynecological practices in Belgium., Methods: Forty-six, 18- to 50-year-old premenopausal women with a disrupted vaginal flora due to a bacterial vaginal infection (bacterial vaginosis, aerobic vaginitis) were included, provided that fresh phase-contrast microscopy of the vaginal fluid showed lactobacillary flora grade 2B or 3. Patients were given a blinded box with either 12 vaginal tablets of Gynoflor® (study medication) or 6 vaginal suppositories containing 500 mg metronidazole (control medication). Eight efficacy variables were studied to assess the status of the vaginal flora at entry, 3-7 days (control 1), 4-6 (control 2) weeks and 4 months after the end of therapy., Results: At control 1, the combined variables equally improved in the lactobacilli group as in the metronidazole group. At control 2, the lactobacillus preparation showed slightly inferior results when compared to metronidazole. At 4 months, this analysis could not be performed due to low numbers, but analysis of recurrence rate and extra medication needed was not different between both groups., Conclusion: Lyophilized lactobacilli in combination with low-dose estriol are equivalent to metronidazole in the short-term treatment of bacterial vaginal infections, but have less effect after 1 month. Further studies are required to evaluate the long-term efficacy of lactobacilli when applied repeatedly., (Copyright © 2010 S. Karger AG, Basel.)

Objective: The goal of this cross-sectional laboratory-based study is to investigate the association between Trichomonas vaginalis (TV) and human papillomavirus (HPV) infections in cervical samples in Flanders., Setting: Liquid-based cervical cytology samples from unselected women, covering a population of 14-97 years of age (n = 62,636), and from professional sex workers of the region of Antwerp (n = 308), all residents of Flanders (North Belgium) and participating in cervical cancer screening, were assessed for the presence of TV and HPV., Methods: During 7 months in 2008, 62,944 consecutive liquid-based cytology cervical cancer screening samples were assessed for cytological abnormalities. All samples were tested by real-time quantitative PCR for the presence of TV as well as for low-risk HPV (lrHPV) types 6, 11, 53, 66 and 67, and high-risk HPV (hrHPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Association between TV and HPV infections with age, geographic area and occurrence of cytologic lesions were investigated., Results: The overall prevalence of TV in the general population in Flanders was 0.37%, with the highest prevalence in women aged 41-45 years (0.53%). HPV was detected in 15.1% of cervical samples and peaked in younger women of ages 21-25 years (26.8%). The prevalence of TV was higher in women with HPV infections as compared to women without HPV (0.61 vs. 0.33%, p < 0.0001). In women of suggestive foreign origin, TV prevalence was 4 times higher than in the probably autochthonous population (1.16 vs. 0.29%, p < 0.0001). Working in the sex industry had an increased risk of both HPV and TV when compared to other women (OR 8.6, 95% CI 4.4-16.9, p < 0.0001) and a higher rate of TV was also observed in urban regions, compared to rural areas (OR 1.7 (1.3-2.2), p = 0.0002)., Conclusion: The prevalence of TV in Flanders is lower compared to data from the literature, whereas the prevalence of HPV infection is similar to that reported in other European countries with similar test systems. Both TV and HPV are sexually transmitted infections, but our prevalence data suggest that the epidemiology of HPV and TV are different in Flanders. Highest HPV prevalence is found in young women whereas TV is more frequent in older women. Although some epidemiological peculiarities of the society, such as promiscuity and import from overseas countries, can possibly account for the differences in epidemiology, the exact reasons remain to be elucidated in further studies., (Copyright © 2010 S. Karger AG, Basel.)