Effectiveness of Two Transcutaneous Electrical Nerve Stimulation (TENS) Protocols in Women with Provoked Vestibulodynia: A Randomized Controlled Trial.

BACKGROUND: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD. METHODS: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements. RESULTS: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% (p = 0.003) and 23.1% in Group 2 (p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant. CONCLUSIONS: Our findings showed the potential of TENS in the treatment of VBD.

The impact of combined contraceptive vaginal ring on vaginal environment: an observational, longitudinal study.

PURPOSE: To assess the relationship between combined contraceptive vaginal ring (CVR) and vaginal microbiome using 16S rRNA gene sequencing. MATERIALS AND METHODS: We enrolled 20 women for 8 weeks in an open-label study using CVR (NuvaRing®) that delivered 15 mcg ethinylestradiol and 120 mcg etonogestrel daily. The vaginal microbiome was assessed at baseline and after 2 months by sequencing the 16S rRNA genes amplified from the total genomic DNA isolated from the sample. RESULTS: Bacterial distribution richness and equity did not significantly change after 2 months, and the dominant bacterial strain was Lactobacillus crispatus. Only one woman with a history of vestibulodynia and recurrent vulvovaginitis showed an increase in bacterial biodiversity, with a switch to the relative abundance of anaerobic bacteria. CONCLUSIONS: Our results suggest that CVR does not adversely affect the composition and structure of the vaginal microbiome. However, special care should be taken in patients with a history of vestibulodynia and/or recurrent vulvovaginal infections.

Contraceptive vaginal ring does not adversely affect vaginal microbiome except in the case of recurrent vulvovaginal infections or vestibulodynia.

Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study.

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.

Characterization of female intimate hygiene practices and vulvar health: A randomized double-blind controlled trial.

BACKGROUND: Inappropriate feminine hygiene practices are related to vulvar unpleasant symptoms (such as skin changes, lesions, burning, pruritus, fissures, and dyspareunia). AIMS: We assessed the daily use effects of intimate cleansers on vulvar skin by comparing two specific products for intimate care: Saugella Hydraserum (SIS), based on natural extracts, and a standard product based on lactic acid, such as Lactacyd Feminine Hygiene (LTC). Forty healthy women were enrolled in this double-blind controlled study. METHODS: After randomization, the cleansers were used twice daily for 30 days. The hydration level was determined using the Corneometer® CM 825, the pH using the Skin-pH-Meter PH 905® and the sebum level using the Sebumeter SM815® . Measurements were performed at baseline and on day 30 on the labia majora and labia minora. RESULTS: Both cleansers showed a reduction in the hydration level, but this was much less evident in the SIS group (-6.3% SIS vs -23,7% LTC). The pH values of the SIS group were lower than those of the LTC group, especially on the labia minora (5.27 ± 0.08 and 5.6 ± 0.1, respectively, P = .025). The sebum increased in both groups, but in the LTC group, it was higher on the labia majora (+96.2% vs +46.8%, respectively, P = .003), while on the labia minora, it was higher in the SIS group (+24.7% vs +17.1%, respectively P = NS). CONCLUSIONS: Both cleansers tested showed high performance for safety and tolerability on vulvar skin, but SIS showed better efficacy than LTC on some parameters.

Features of the Vaginal and Vestibular Microbioma in Patients With Vestibulodynia: A Case-Control Study.

OBJECTIVE: Our objective was to determine the role of vaginal and/or vestibular microbiota disturbance as an associated factor of symptom characteristic of provoked vestibulodynia (PVD). STUDY DESIGN: In an observational case-control study, the bacterial microbiomes in the vagina and vestibule from 20 women with PVD and 18 healthy controls were compared using a 16S rRNA gene-based molecular analysis. Clinical data were recorded through a 0- to 10-point visual analog scale related to dyspareunia and vulvovaginal pain/burning. RESULTS: Comparative assessment of the bacterial taxa (cutoff ≥15%) revealed 105 genera in the vaginal samples of PVD patients and 113 genera in the vestibular samples. Similarly, 120 genera were detected in the vaginal samples and 151 in the vestibular samples of the control group. Bacterial complexity was higher in the vestibular samples than in vaginal samples in both groups, without statistically significant differences. The following 3 dominant taxonomic units were found: Lactobacillus, Gardnerella, and Atopobium in PVD patients and Lactobacillus, Gardnerella, and Bifidobacterium in the control group. Lactobacillus gasseri was dominant only in women with PVD, showing a significant correlation with burning/pain intensity and dyspareunia severity (0.255 and 0.357, respectively, p < .001). CONCLUSIONS: Our data suggest that bacterial communities in vaginal discharge are an important contributor to the vestibular microbiota. Lactobacillus gasseri may be an element of vulnerability toward the development of vaginal dysbiosis. We can postulate its association as a potential etiologic organism in some individuals, either by itself or in some combination with other trigger factors.

Vaginal diazepam plus transcutaneous electrical nerve stimulation to treat vestibulodynia: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of vaginal diazepam in addition to transcutaneous electrical nerve stimulation (TENS) in the treatment of vestibulodynia (VBD). STUDY DESIGN: This study was a randomized, double-blind, placebo-controlled trial. Forty-two patients with VBD were randomized, 21 underwent diazepam and TENS (diazepam group) and 21 received placebo and TENS (placebo group). Vulvar pain was assessed on a on a 10-cm visual analogue scale (VAS) and dyspareunia according to the Marinoff dyspareunia scale. Vaginal surface electromyography (EMG) and vestibular current perception threshold (CPT) testing were performed at baseline and 60 days after treatment. The primary endpoints included the change in pain and dyspareunia from baseline to 60 days of pain and dyspareunia. The secondary endpoints was the variation in objectivity of pelvic floor muscle (PFM) function and vestibular nerve fiber current perception threshold (CPT). RESULTS: The VAS scores for pain from basal values of 7.5 and 7.2 for the diazepam and placebo, respectively, showed significant (p 0.01) decreases from 4.7 to 4.3, but this difference was not statistically significant. The Marinoff dyspareunia scores in the diazepam group showed a significant difference (p 0.05) from values measured in the placebo group. The ability to relax the PFM after contraction (difference between maximal contraction and rest tone) was significantly greater for the diazepam group versus the placebo group (3.8 µv and 2.4 µv, respectively, p 0.01). The CPT values for all of the nerve fibers increased after the treatment, but this increase was significant in the diazepam group only for the values at a 5-Hz stimulation (C fibers) with a change of 47.8% vs 26.9% (p < 0.05). Only two patients reported a mild drowsiness in the diazepam group. CONCLUSIONS: The present study provided indications that vaginal diazepam plus TENS is useful to improve pain and PFM instability in women with VBD.

Thymol, eugenol and lactobacilli in a medical device for the treatment of bacterial vaginosis and vulvovaginal candidiasis.

The aim of this non-interventional, observational, multicentre, open-label study was to assess the effectiveness of a vaginal gel containing extracts of Thymus vulgaris and Eugenia caryophyllus in conjunction with two specific lactobacilli strains (Lactobacillus fermentum LF10 and Lactobacillus plantarum LP02) specifically formulated in slow-release vaginal capsules, in treating bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) or recurrent vulvovaginal candidiasis disease (RVVC) [Estromineral Probiogel (EPB) in Italy, or Saugella Probiogel; Meda Pharma - Mylan Group]. There was a statistically significant improvement in pruritus, burning, vulvovaginal oedema and erythema, dyspareunia and vaginal secretions in all diagnostic groups. At the end of the study, the microbiological evaluation was normal in 80.0% of cases with BV, 62.5% of cases with VVC and 100.0% with RVVC. The clinical data allow EPB to be recommended in the acute treatment of VVC and BV, suggesting that EPB is a useful maintenance treatment if there are recurrent episodes. Controlled studies are needed to confirm the efficacy of EPB in the treatment of recurrences and to identify the most appropriate dosage regimen.

Vulvar vestibular effects of ospemifene: a pilot study.

The study aimed to assess the effects of ospemifene on vulvar vestibule in postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of the vulvar vestibule was also conducted. Patients also underwent current perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five patients (94.6%) completed the treatment. Hot flashes were the most frequent adverse effects, but this led to a discontinuation of therapy in three patients (5.4%). After therapy, there was a statistically significant decrease from the baseline in the mean scores for dryness, burning, and dyspareunia and reduction of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p ≤ 002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a difference in CPT values for all nerve fibers and more consistent for C fibers (-38% of sensitivity). These results confirm the efficacy of ospemifene on postmenopausal vestibular symptoms and signs; moreover, the drug was effective in normalizing vestibular innervation sensitivity.

Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule?

OBJECTIVE: The aim of this study was to evaluate the effectiveness of the application of 0.005% estriol gel to the vulvar vestibule in the management of postmenopausal dyspareunia. STUDY DESIGN: Postmenopausal women with dyspareunia were enrolled in this study. Patients were instructed to use a fingertip to apply 0.25g of vaginal gel containing 25µg of estriol to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. RESULTS: Assessment of symptoms (dyspareunia and cotton swab test) and signs of vestibular atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 63 women were included. Of the 63, 59 (93.6%) completed the 12-week treatment period, and four dropped out for vestibular burning. Dyspareunia improved or was cured (score ≤1) by week 12 in 81.4% of patients. The patients also showed a statistically significant reduction in vestibular atrophy and cotton swab test at the end of treatment. CONCLUSIONS: Application of 0.005% estriol gel to the vulvar vestibule is effective in correcting menopausal coital pain. This suggests that reduction in sensory vestibular innervation sensitivity is likely to play a pivotal role in the relief of dyspareunia. One limitation of this study is the limited follow-up, but the therapy may be continued for as long as the patients are distressed by their symptoms without estrogen intervention.

A case of ultrasound diagnosis of fetal hiatal hernia in late third trimester of pregnancy.

Congenital hiatal hernia is a condition characterized by herniation of the abdominal organs, most commonly the stomach, through a physiological but overlax esophageal hiatus into the thoracic cavity. Prenatal diagnosis of this anomaly is unusual and only eight cases have been reported in the literature. In this paper we describe a case of congenital hiatal hernia that was suspected at ultrasound at 39 weeks' gestation, on the basis of a cystic mass in the posterior mediastinum, juxtaposed to the vertebral body. Postnatal upper gastrointestinal tract series confirmed the prenatal diagnosis. Postnatal management was planned with no urgency. Hiatal hernia is not commonly considered in the differential diagnosis of fetal cystic chest anomalies. This rare case documents the importance of prenatal diagnosis of this anomaly for prenatal counseling and postnatal management.

Vulvar lichen sclerosus: a comparison of the short-term topical application of clobetasol dipropionate 0.05% versus mometasone furoate 0.1%.

OBJECTIVE: To compare the efficacy of the short-term application of clobetasol propionate 0.05% (CLB) and mometasone furoate 0.05% (MMF) in the treatment of vulvar lichen sclerosus (VLS). STUDY DESIGN: This study was a retrospective review of 96 women who were diagnosed with lichen sclerosus with a follow-up of at least 1 year. Of these 96 women, 47 were treated with the topical application of CLB and 49 were treated with the topical application of MMF. All patients received treatment for 8 weeks. The drug was administered once daily for 4 weeks and then twice weekly for another 4 weeks in combination with a moisturizing cream that was continued as maintenance therapy. Subsequently, a topical steroid was applied on an as-needed basis if symptoms recurred. Follow-up visits were scheduled at 3, 6, and 12 months. The primary endpoint was the clinical response of the patients. RESULTS: A mean of 77.3% of the patients were defined as responders at the 12-month observation, without any significant difference between the 2 treatment groups (CLB mean 73% vs MMF mean 81.6%, p = .2). A pronounced improvement in itching was observed after 3 months of treatment in the MMF group (p = .04), whereas the other symptoms were not significantly different between the 2 groups. CONCLUSIONS: This study indicates that CLB 0.05% and MMF 0.1% in a short protocol regimen are effective, safe, and reliable treatments for VLS, with no significant difference between the 2 steroids in their efficacy. However, a moisturizing cream should be an integral part of the treatment.

Assessment of fetal inflammatory syndrome by "classical" markers in the management of preterm labor: a possible lesson from metabolomics and system biology.

There exists a huge gap between protocols issued by scientific bodies and evidence derived by system biology studies on the multifactorial origin of threatened preterm delivery and their different associations with neonatal outcome. The objective of this prospective study was the analysis obstetrical and neonatal outcome in a cohort of pregnant patients treated for the risk of preterm delivery according to maternal and fetal assessment determined by amniotic fluid samples. Methods. Threatened preterm delivery and premature rupture of membranes between 24 + 1 and 32 + 6 weeks of gestation were treated by prolonged tocolytic regimens and if necessary by antibiotics for maternal infections when intra-amniotic inflammation (IAI) was excluded on the basis of negative white blood cell count in the amniotic fluid, or opposite, by delivery after a course of betamethasone and 48 hours maintenance tocolysis. Twenty-three cases were compared with 22 historical controls treated by the same teams according to the 48 hours treat and wait criteria. In addition to this, cases with normal and abnormal amniotic fluid white blood cell were compared. Results. Maternal and fetal conditions at admission were not significantly different between the study and control cohort for all maternal and fetal variables. Clinical indices were significantly improved as regard to latency from admission to delivery, number of newborns admitted to neonatal intensive care unit and length of stay in neonatal intensive care unit. Not any perinatal death or sepsis occurred in the study cohort. Overall, improved neonatal outcomes were observed in the study cohort. Composite major neonatal eventful outcomes occurred in 26% of cases vs. 50% in controls. The limited number of cases was not powered enough to reach a statistical significance for these variables. Continued tocolysis on demand and full regimen of mono or combined antibiotic regimen for maternal infection achieved significantly longer delay between admission to delivery with improved in neonatal outcome in cases negative for IAI: only 2 of 14 newborns suffered of major neonatal complications vs. 4 of 9 newborns delivered for IAI. Conclusions. Fetuses without IAI can be treated conservatively and their stay in utero prolonged without harm. However, we confirmed that when IAI is already active in utero a worse neonatal outcome is already partly predetermined. These positive findings must be interpreted with cautions given the limited number of cases considered by this study.

Accumulation of retinoid X receptor-alpha in uterine leiomyomas is associated with a delayed ligand-dependent proteasome-mediated degradation and an alteration of its transcriptional activity.

An alteration of the retinoid pathway can influence the development of uterine leiomyomas in animal models, and retinoids have shown efficacy in inhibiting the growth of this benign tumor both in vitro and in vivo. However, the underlying mechanisms and biological implications are unclear. The present study was based on the demonstration of an accumulation of full-length retinoid X receptor alpha (RXRalpha) in leiomyomas that was not associated with a modification of its gene expression. This accumulation was shown to increase the transcription of the RXR-responsive gene cellular retinoic acid binding protein II (CRABP-II) and to be linked to the cellular redistribution of the receptor and to its retarded degradation via the ubiquitin/proteasome pathway. Accordingly, treatment with a specific proteasome inhibitor but not with protease inhibitors strongly inhibited the degradation of full-length RXRalpha in cells deriving from both myometrium and leiomyoma, but the formation of RXRalpha/ubiquitin conjugates was differentially regulated between the two cell types. Moreover, full-length RXRalpha accumulated in leiomyomas was abnormally phosphorylated at serine/threonine residues relative to myometrial tissue. The ligand to RXRalpha, 9-cis-retinoic acid, induced the receptor breakdown in smooth muscle cells deriving from both normal and tumor tissue, whereas a MAPK-specific inhibitor was able to reduce RXRalpha levels only in leiomyoma cells. These results suggest that switching of the ubiquitin/proteasome-dependent degradation of RXRalpha by phosphorylation in leiomyomas may be responsible for the accumulation of the receptor and the consequent dysregulation of retinoic acid target genes. The ability of retinoids to modify this molecular alteration may be the rationale for their use in the treatment of leiomyomas.