Search Results (2,370)

Symptomatic vulvovaginal candidiasis (VVC) affects around three-quarters of women at least once in their lifetime. Around 10% of these women will experience prolonged or recurrent vulvovaginal candidiasis (RVVC), which fails to respond, despite following recommended therapy. Most commonly prescribed therapy involves suppression therapy—usually for two weeks—which aims at eliminating symptoms by frequent administration of antifungals, followed by maintenance (weekly/monthly) therapy for up to six months. However, following cessation of maintenance therapy, around 50% of these women experience relapse. The vaginal ecology of RVVC can be characterized, and it is thought that biofilms and/or the development of antifungal resistance prevent adequate resolution. However, hypersensitivity may also confound management. This narrative review was performed to identify key studies that examine the management of VVC and the challenges of current prolonged antifungal therapy. It identifies gaps that show it remains important to investigate microbiological findings in RVVC and how these may inform rational choices in therapy in an era of rising antimicrobial resistance. Hope exists, as studies of the vaginal microbiome highlight that the type of microbiota may influence the level of inflammation and reduce symptomatology. Future research will continue to explore whether a personalized medicine approach can promote healthy vaginal ecology and prevent the debilitating long-term effects of RVVC. Full article

Vulvovaginal candidiasis (VVC) is a prevalent vaginal infection predominantly attributed to Candida albicans. A considerable proportion of women experience more than three episodes of VVC annually, a condition referred to as recurrent vulvovaginal candidiasis (RVVC). It is estimated that RVVC affects more than 130 million women globally each year and has a substantial negative impact on their quality of life, resulting in physical discomfort, psychological distress, and social stigma. Nevertheless, not all individuals who develop VVC progress to RVVC, suggesting that genetic variation may play a critical role in host susceptibility. The present review aims to evaluate the associations between genetic predispositions—specifically polymorphisms in Toll-like receptors 2 and 4 (TLR2, TLR4)—and RVVC. TLRs are essential for detecting pathogen-associated molecular patterns (PAMPs) and initiating immune responses. During RVVC episodes, Candida undergoes a reversible transition from the yeast form to the hyphal form, resulting in alterations in surface PAMPs, which are subsequently recognized by innate immune receptors expressed on vaginal epithelial cells. Polymorphisms in these receptors may modulate individual susceptibility to RVVC. This review examines the literature on the impact of specific polymorphisms in TLR2 and TLR4 on fungal recognition and infection. Furthermore, the interactions between TLRs and other elements of the innate immune system have also been explored. A deeper understanding of how genetic variability in immune receptors influences infection susceptibility could pave the way for personalized therapeutic strategies for RVVC, potentially involving immunomodulatory agents or antifungal treatments tailored to an individual’s genetic profile. Full article

Background/Objectives: Adolescent girls and young women (AGYW) have a high burden of sexually transmitted infections (STIs). This study examined the prevalence of Chlamydia trachomatis, its association with human papillomavirus (HPV), and other associated factors among AGYW of rural communities. Methods: Secondary data on C. trachomatis, HPV, and linked questionnaires from 214 sexually active AGYW were used. Self-collected vaginal specimens were previously tested using the Allplex™ STI Essential Assay and Roche Linear Array HPV genotyping assay. Results: The overall prevalence of C. trachomatis was 29.4% (63/214), and it was not influenced by age. The majority of the AGYW were C. trachomatis negative and HPV positive (52.4%, 111/212), followed by being C. trachomatis and HPV co-infected (23.6%, 50/212), C. trachomatis and HPV co-negative (18.4%, 39/212) and least were C. trachomatis positive and HPV negative (5.7%, 12/212). There was an increased prevalence of being HPV infected among C. trachomatis individuals than being C. trachomatis positive among HPV positive individuals (RR: 2.60, 95% CI: 2.00–3.38, p < 0.0001). C. trachomatis positive AGYW had a significantly higher association of HPV types targeted by Cervarix^® HPV vaccine (HPV-16 and/or -18) than C. trachomatis negatives (RR: 2.58, 95% CI: 1.37–4.82, p = 0.005), targeted by Gardasil^®4 HPV vaccine (HPV-6, -11, -16 and/or -18; RR: 2.21, 95% CI: 1.32–3.65, p = 0.005) and Gardasil^®9 HPV vaccine (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58; RR: 1.92, 95% CI: 1.37–2.67, p < 0.001). Conclusions: There was a high burden of C. trachomatis and HPV coinfection. C. trachomatis coinfection influenced HPV genotype prevalence and distribution, including those that are targeted by the current commercial HPV vaccines, suggesting that the high burden of C. trachomatis among AGYW may pose challenges to the ongoing HPV vaccination program. Integrated STI screening and prevention strategies are needed in rural South African settings. Full article

Achieving satisfactory levels of weight gain for developing replacement beef heifers is challenging when utilizing toxic endophyte-infected tall fescue (Schedonorus arundinaceus) as the primary forage. This is due to the intensifying impact of ergot alkaloids produced by the fungal endophyte on heifer heat stress in the summer. The purpose of this trial was to determine if clipping hair coats would reduce heat stress impacts experienced by fall-born heifers stocked on toxic endophyte-infected tall fescue. Heifers were randomly assigned to a control cohort and a clipped cohort. The heifers in the clipped treatment group were sheared along the body of the heifer. Vaginal temperature loggers were used to record core temperatures every ten minutes during several sampling periods. Hair coats on clipped heifers resembled hair coats of the control heifers by the conclusion of the 16-week trial. Average daily gains of the clipped heifers exceeded the average daily gains of the control heifers only in the first four-week period. There were no differences in seasonal average daily gain or pregnancy rates. Clipped heifers had cooler core temperatures by 0.2–0.3 °C in the morning compared to the control heifers. Clipping hair coats of heifers only provided short-term relief for cattle stocked on toxic endophyte-infected tall fescue. Full article

Background: Stress urinary incontinence (SUI) is the involuntary loss of urine during increased abdominal pressure, affecting 46% of adult women, particularly those over 40. Pelvic floor muscle (PFM) training is the first-line treatment supported by numerous high-quality studies. However, the effectiveness of biofeedback devices, such as vaginal weight cones, remains controversial. Peflex weights are a new type of vaginal extracorporeal weights developed for PFM training. Aims: To evaluate the effectiveness of PFM training with Peflex weights in reducing SUI symptoms, improving muscle power and endurance, and comparing its efficacy to standard PFM training without weights. Methods: A pilot randomized controlled trial was conducted involving 35 women aged 18 to 50 diagnosed with SUI. Participants were randomly assigned to either the Peflex group (PFM training with Peflex weights) or the control group (PFM training without weights). Both groups engaged in six weeks of home-based training. The primary outcome was assessed using the self-reported International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF). Secondary outcomes included evaluations based on the PERFECT scheme, perineometer measurements, and levator hiatus diameters obtained via ultrasound. Results: In the intragroup analysis, the Peflex group significantly improved all outcome measurements. Compared to the control group, the Peflex group demonstrated significantly higher improvement in muscle power and repetition of muscle contraction (p = 0.015 and p = 0.007, respectively), as well as in the proportional change in levator hiatus contraction (p = 0.022). There was no significant difference in the improvement in ICIQ-UI-SF and perineometer measurements between the groups (p > 0.05). Additionally, there was a trend of higher satisfaction with the treatment in the Peflex group (p = 0.054). Conclusions: Peflex weights effectively reduce SUI symptoms and improve muscle power and endurance, with high user satisfaction. However, there was no significant difference in the main outcome measure (ICIQ-UI-SF) between the Peflex and control groups. Further research is needed to identify which patients benefit most from this treatment. Full article

Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium dioxide (TiAB) against multidrug-resistant bacteria isolated from dermatological infections. Objectives: We evaluated whether TiAB, at concentrations used in marketed medical devices, exerts antibacterial and antifungal effects against clinically relevant vaginal isolates by determining Minimum Inhibitory Concentration/ Minimum Bactericidal and Fungicidal Concentration (MIC, MBC/MFC), and time–kill kinetics. Methods: A total of 73 clinical isolates were collected from vaginal swabs, including Staphylococcus aureus (MSSA, MRSA), Escherichia coli (ESBL+ and non-ESBL), Klebsiella pneumoniae, Enterococcus spp., Streptococcus agalactiae, and Candida albicans. Minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBCs/MFCs) were determined by broth microdilution, and bactericidal activity was confirmed by time-kill assays. Results: TiAB exhibited potent activity against Gram-negative bacteria, with median MIC values of 1–2% (w/v) for E. coli and K. pneumoniae. Gram-positive isolates, including S. agalactiae and Enterococcus spp., showed higher MIC values (2–4%). Candida albicans displayed fungistatic inhibition at 4%. Time-kill assays confirmed rapid bactericidal effects for Gram-negative isolates within 8 h at 2× MIC, while Gram-positive bacteria required prolonged exposure. Conclusions: These findings extend previous evidence of TiAB’s antimicrobial properties to gynecological pathogens, supporting its potential as a topical, non-antibiotic option for managing vaginal infections in an era of rising antimicrobial resistance. Further in vivo validation is warranted. Full article

Background: Levofloxacin is a broad-spectrum third-generation fluoroquinolone with bactericidal activity against Streptococcus species. We aimed to investigate the susceptibility rates of levofloxacin, the genetic determinants contributing to resistance, the serotype distribution, and the population structure of levofloxacin-resistant Streptococcus agalactiae (GBS) isolates. Methods: Antibiotic susceptibility testing was conducted according to the EUCAST criteria. PCR-serotyping, determination of mutations in the quinolone resistance-determining regions (QRDRs), and multi-locus sequence typing (MLST) were performed on all levofloxacin-resistant strains. Results: Among the 328 GBS isolates, 11.9% exhibited resistance to levofloxacin. We categorized the samples into two main groups: vaginal (64.1%) and extra-vaginal. The latter was further subdivided into invasive (10.3%) and non-invasive (25.6%) ones. The most common serotypes identified were V (30.8%) and III (25.6%). All examined resistant strains possessed missense mutations in the QRDR of parC (Ser79Phe/Tyr and Asp83Asn), whereas 59.0% of them exhibited additional mutation in gyrA (Ser81Leu and Glu85Lys/Ala). The MLST results disclosed six clonal complexes: CC19(64.1%), followed by CC1 (10.3%), CC452 (7.7%), and CC459 (5.1%), and CC12 and CC23, represented by single strains. Conclusions: We observed a growing resistance to fluoroquinolones that appears to exceed the average in Europe. More than half of the isolates exhibited the accumulation of mutations within the QRDRs. Rigorous monitoring is needed to prevent the emergence of MDR GBS and preserve the effectiveness of the newer generations of fluoroquinolones. Full article

Additional progesterone administration during the luteal phase enhances reproductive outcomes in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles in patients with low serum progesterone (P4). In this study we wanted to explore the use of urine P4 as a diagnostic tool during the luteal phase. This prospective observational cohort included a total of 464 HRT-FET cycles. The protocol entailed oral oestradiol (6 mg/24 h), followed by vaginal micronised progesterone (400 mg/12 h). On the day of blastocyst transfer, urine and serum samples were collected. Urine samples were analysed using an ARCHITECT automated immunoassay. A significant difference was found in median urine P4 between patients with serum P4 higher or lower than 11 ng/mL: 6400 ng/mL IQR [2528; 11,930] vs. 3408 ng/mL IQR [592; 6688], p < 0.001. The optimal cut-off to achieve live birth was a urine P4 ≥ 4000 ng/mL. The live birth rate was significantly higher in patients with urine P4 ≥ 4000 ng/mL, 48% (107/222) vs. 35% (45/130), respectively (p = 0.013). The odds ratio for live birth was 1.8 in patients with urine P4 ≥ 4000 ng/mL, 95% CI [1.067; 3.018], p = 0.028. The findings of the present study suggest that urine progesterone could be a valuable diagnostic tool to evaluate the need for additional progesterone in HRT-FET cycles. Full article

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide. This study investigated six single-nucleotide polymorphisms (SNPs) in the maternal and fetal progesterone receptor (PGR) gene and their association with spontaneous PTB, considering environmental and clinical risk factors. We conducted a case–control study including two groups of pregnant women (term and preterm, 292 in total) and two groups of newborns (term and preterm, 292 in total), and analyzed PGR variants (rs1042838, rs1042839, rs10895068, rs4574732, rs653752, and rs1942836) in relation to maternal age, fetal gender, and pregnancy complications such as vaginal bleeding. Results showed that PGR SNPs rs1942836 (OR 0.38, CI 95% 0.15–0.98, p = 0.03), rs4574732 (OR 2.4, CI 95% 1.01–5.57, p = 0.04), and rs653752 (OR 2.27, CI 95% 1.19–4.34, p = 0.02) were associated with PTB when considered in the context of clinical factors, highlighting gene–environment interactions. Our findings underscore the importance of integrating genetic and clinical information for a better understanding of PTB risk. Full article

Background/Objective: Dyspareunia negatively affects women’s lives. Up to 35% suffer from postpartum dyspareunia. Many factors may influence the occurrence of postpartum dyspareunia, but little is known about them. This study aimed to look at the frequency of dyspareunia one year postpartum in a cohort of primiparae. Which perinatal factors influence the frequency of postpartum dyspareunia? Methods: A total of 3264 primiparae were included in this observational cohort study. Perinatal factors were documented, and a specially designed questionnaire was sent to them one year postpartum. The primary outcome was the frequency of dyspareunia one year postpartum. The secondary outcomes included potential influencing factors such as birthing method (spontaneous bed delivery, spontaneous delivery other than bed, water delivery, and vacuum-assisted delivery); perineal injuries (first- and second-degree perineal tears, obstetric anal sphincter injuries (OASIs), and episiotomies); and the use of oxytocin. Results: Postpartum dyspareunia was observed in 15% of the 3264 primiparae. In multivariate analysis, there were influences found in the perineal injury group, especially for first- and second-degree perineal tears and OASIs. In the oxytocin group, a trend toward a higher rate of postpartum dyspareunia was observed. No influence of the different birthing methods was found. Conclusions: Postpartum dyspareunia, affecting 15% of women one year after vaginal delivery, is associated with perineal injuries, particularly minor perineal tears and OASIs. This highlights the importance of good preparation of the perineum and pelvic floor before delivery, efficient perineal protection during labor, and the use of a precise repair technique for all perineal injuries. Full article

Chlamydia trachomatis (CT) remains the most commonly reported bacterial sexually transmitted infection (STI) globally, with particularly high incidence among adolescents and young adults. In Europe, CT cases have continued to rise over the past decade, despite ongoing public health efforts in prevention and screening. Screening coverage, however, remains inconsistent across countries. CT infections are often asymptomatic, especially in women, yet can lead to serious CT-related reproductive complications if left untreated, including pelvic inflammatory disease (PID), tubal factor infertility, and ectopic pregnancy. Emerging evidence highlights the cervicovaginal microbiota as a key factor influencing susceptibility to STIs, including CT infection, its progression, and associated outcomes. A Lactobacillus-dominated microbiota, particularly L. crispatus, is well-known to be a protective factor against CT acquisition, whereas vaginal dysbiosis, characterized by a depletion of these species and an overgrowth of anaerobes, such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella spp., has been linked to increased CT acquisition risk, reduced immune control, and impaired infection resolution. Interaction between microbial communities and host immunity may modulate whether CT infections spontaneously clear, persist, or progress into pathological conditions. This review explores the natural history of CT genital infection in women, emphasizing the role of cervicovaginal dysbiosis in disease progression and reproductive sequelae. By integrating current knowledge about resident cervicovaginal microbes, host-microbe interaction, and CT-related reproductive outcomes, we discuss how microbiota-targeted strategies, including probiotic or microbiome-modulating strategies, may complement current CT prevention, diagnosis, and treatment approaches. Full article

Candida species are common commensals within the human microbiome but can transition opportunistically to pathogenic states when host–microbe homeostasis is disrupted. Their ability to adhere to mucosa and implanted medical devices, form thick biofilms, and invade epithelial tissues makes candidiasis particularly harmful in immunocompromised and elderly populations. This review examines the reported antifungal activity of common probiotic genera such as Lactobacillus, Bacillus, Bifidobacterium, and Saccharomyces across the oral cavity, gastrointestinal tract, and vaginal tract. The probiotic mechanisms of action, such as competitive exclusion, secretion of antifungal metabolites, and immunomodulation, are explored in detail, and research methodologies are scrutinised to assess the robustness of current evidence. This review compiles evidence from a variety of studies and clinical trials showing certain probiotic strains and formulations have the ability to significantly decrease Candida colonisation and reduce candidiasis symptom prevalence. Although outcomes vary greatly between probiotic strains tested, species of Candida targeted, and specific site of infection, it is clear that selected probiotic species and their secreted substances can have prominent anti-Candida effects and promote tangible clinical improvements. Future directions for the field of probiotic study are suggested, including the roles of prebiotics, postbiotics, and synbiotic formulations to enhance probiotic efficacy against candidiasis. Full article

Objective: This narrative review aims to summarize current evidence on the epidemiology, risk factors, clinical patterns, and therapeutic strategies for urinary incontinence in menopausal women. Background: Urinary incontinence (UI) is a common, multifactorial condition that disproportionately affects women, with prevalence rising during pregnancy and post menopause. While stress urinary incontinence (SUI) predominates in younger and early postmenopausal women, urgency urinary incontinence (UUI) and mixed urinary incontinence (MUI) become increasingly prevalent with age and duration following menopause. Additional determinants, such as obesity, comorbidities, polypharmacy, and menopausal symptoms, burden further contribute to symptom severity and persistence. Materials and Methods: For the materials and methods, we used over 150 specialized studies and meta-analyses published in the specialized literature on this subject, of which 99 are mentioned in the bibliography of this narrative review. These materials are some of the most significant and up-to-date that address this complex topic. Content: This narrative review discusses the impact of menopause-related hormonal decline on the genitourinary tract, highlighting the role of estrogen deficiency in genitourinary syndrome of menopause (GSM). It addresses distinct patterns of UI across life stages, including pregnancy and the early and late postmenopause periods, and explores modifiable risk factors such as body mass index. Specific attention is given to nocturnal incontinence, medication-related effects, and coital incontinence, which significantly impair sexual health and quality of life. Therapeutic strategies are presented in a stepwise manner: conservative measures (pelvic floor muscle training), hormonal approaches (local vaginal estrogen), combination regimens, and surgical interventions, including midurethral slings, colposuspension, bulking agents, and neuromodulatory techniques. Future perspectives: Emerging modalities such as balneotherapy and energy-based therapies show promise but require further investigation. Conclusions: Urinary incontinence in menopausal women is best addressed through an individualized, multimodal approach that integrates conservative, hormonal, minimally invasive, and surgical options. Combination therapies demonstrate superior efficacy in addressing both continence and GSM-related symptoms. Future research should refine patient selection, optimize multimodal treatment algorithms, and prioritize long-term outcomes and quality-of-life measures in clinical decision-making. Full article

The rising resistance of bacterial and fungal strains, particularly in biofilm form, is diminishing the efficacy of available therapies and poses a major threat to human health. This highlights the need for new antimicrobial agents. A review of biological studies has shown that 2,7-naphthyridine derivatives exhibit a wide spectrum of pharmacological properties, including antimicrobial activity, which has contributed to the development of new compounds containing this scaffold. In this work, the obtained compounds were tested to assess their ability to eradicate biofilm formed by selected reference strains of opportunistic pathogens: Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans as well as towards normal microbiota representative, referred to as the Lactobacillus crispatus. The tested 2,7-naphthyridine derivatives showed selective antimicrobial activity, exclusively against S. aureus. 10j demonstrated the highest, among tested compounds, activity on this pathogen (MIC = 8 mg/L), while compound 10f exhibited ~100-fold stronger activity (MIC = 31 mg/L) than the majority of the library compounds. The in vitro assessment on fibroblast cell lines demonstrated low cytotoxicity of both compounds 10f and 10j, which was subsequently confirmed in vivo using the Galleria mellonella larval model, where no signs of systemic toxicity were observed during the 5-day observation period. Due to the structural similarity of the compounds 10f and 10j to typical gyrase/topoisomerase IV inhibitors, molecular dynamics simulations were performed on a ternary complex containing protein, DNAds, and a 1,5-naphthyridine inhibitor (PDB ID: 6Z1A). Molecular dynamics of the gyrase–DNA ternary complex supported stable binding of both hydrazone derivatives, with 10j showing slightly more favorable MM/GBSA energetics driven by electrostatics and halogen bonding, consistent with its ~4-fold lower MIC versus 10f. Taken together, our data highlight compound 10j as a promising microbiota-sparing antibacterial candidate, particularly suitable for selective interventions against S. aureus, for instance in vaginal infections, where targeted eradication of the pathogen without disturbing protective commensals is highly desirable. Full article

The utility of bioresponsive multifunctional hydrogel compositions for biomedical applications is rapidly increasing due to the diverse array of biological stimuli that can profoundly alter physicochemical gel properties that benefit therapeutic interventions. The purpose of this research is to explore a bioresponsive hydrogel as a drug-free bioengineering concept to fortify the natural physical contraceptive barriers at the cervicovaginal junction. The results of this research demonstrate that a hydrogel comprising 4% (w/w) Carbopol^® 974P and 4% (w/w) polyvinylpyrrolidone (CP4%/PVP4%) undergoes bioresponsive structural changes in the presence of simulated seminal fluid, pH 7.7, (SFS) that increases the work required to spread the gel under physiologically relevant vaginal conditions. Combination of this bioresponsive hydrogel with liquified human semen at a volumetric ratio of 1:5 dramatically reduces in vitro sperm migration by 97%. Simultaneously, total sperm motility decreases from 72.0 ± 9.9% to 7.9 ± 13.7%, which is significantly below the WHO criteria defined for male fertility. Safety assessments performed in vitro and in vivo underline a robust vaginal safety profile comparable to approved vaginal products. Moreover, the results from an exploratory animal study performed with female New Zealand White rabbits suggest that the drug-free physical barrier established intravaginally after exposure of the bioresponsive CP4%/PVP4% hydrogel to alkaline semen seems at least equivalent in the prevention of pregnancy in vivo to the VCF^® Gel (Apothecus Pharmaceuticals, Ronkonkoma, NY, USA), a marketed spermicidal on-demand product containing nonoxynol-9. Full article