Vaginal Conditions Research Articles

Histopathology Role in Females’ vaginal health: A mixed-method study

This study explores the pivotal role of histopathology in assessing and managing female vaginal health conditions through a mixed-method approach. Findings reveal correlations between histopathological features and clinical outcomes, emphasizing the diagnostic accuracy and therapeutic implications of histopathological analyses. Insights from studies on the vaginal microbiome, cervical cancer, endometrial histopathology, and uterine cervix lesions underscore the significance of histopathology in personalized treatment strategies and prognostic assessments. Integrating quantitative and qualitative data, this research enhances our understanding of histopathology's impact on gynecological pathology, leading to improved patient care and outcomes.

Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential.

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.

Effects of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity and sexual function of cervical cancer survivors

Background Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. Methods A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. Results Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. Conclusions Cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment.

Vaginal community state types (CSTs) alter environmental cues and production of the Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1).

Menstrual toxic shock syndrome (mTSS) is a rare but life-threatening disease associated with the use of high-absorbency tampons. The production of the Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1) superantigen is involved in nearly all cases of mTSS and is tightly controlled by regulators responding to the environment. In the prototypic mTSS strain S. aureus MN8, the major repressor of TSST-1 is the carbon catabolite protein A (CcpA), which responds to glucose concentrations in the vaginal tract. Healthy vaginal Lactobacillus species also depend on glucose for both growth and acidification of the vaginal environment through lactic acid production. We hypothesized that interactions between the vaginal microbiota [herein referred to as community state types (CSTs)] and S. aureus MN8 depend on environmental cues and that these interactions subsequently affect TSST-1 production. Using S. aureus MN8 ΔccpA growing in various glucose concentrations, we demonstrate that the supernatants from different CSTs grown in vaginally defined medium (VDM) could significantly decrease tst expression. When co-culturing CST species with MN8 ∆ccpA, we show that Lactobacillus jensenii completely inhibits TSST-1 production in conditions mimicking healthy menstruation or mTSS. Finally, we show that growing S. aureus in "unhealthy" or "transitional" CST supernatants results in higher interleukin 2 (IL-2) production from T cells. These findings suggest that dysbiotic CSTs may encourage TSST-1 production in the vaginal tract and further indicate that the CSTs are likely important for the protection from mTSS.IMPORTANCEIn this study, we investigate the impact of the vaginal microbiota against Staphylococcus aureus in conditions mimicking the vaginal environment at various stages of the menstrual cycle. We demonstrate that Lactobacillus jensenii can inhibit toxic shock syndrome toxin-1 (TSST-1) production, suggesting the potential for probiotic activity in treating and preventing menstrual toxic shock syndrome (mTSS). On the other side of the spectrum, "unhealthy" or "transient" bacteria such as Gardnerella vaginalis and Lactobacillus iners support more TSST-1 production by S. aureus, suggesting that community state types are important in the development of mTSS. This study sets forward a model for examining contact-independent interactions between pathogenic bacteria and the vaginal microbiota. It also demonstrates the necessity of replicating the environment when studying one as dynamic as the vagina.

PH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells

Women are more susceptible to HIV transmission through unprotected heterosexual intercourse due to biological and social vulnerabilities. Intravaginal delivery of siRNAs targeting viral genes, host genes, or in combination has shown promising outcomes against HSV, HPV and HIV. Therefore, in this study, we designed, developed and evaluated a pH-sensitive RNAi-based combination nanomicrobide for the prevention/reduction of vaginal transmission of HIV. The nanomicrobide was composed of siRNA-PEI encapsulated PLGA-PEG nanoparticles (siRNA NP) loaded in a HEC gel dosage form with siRNA targeting host gene CCR5 and the viral gene Nef as a dual preventive strategy. Knocking down CCR5, a co-receptor for HIV could prevent HIV from attaching to and entering host cells and knocking down Nef could reactivate autophagy that was inhibited by Nef to improve the elimination of intracellular virus that escaped the first line of defense. The siRNA NP showed a desirable particle size and zeta potential for intravaginal delivery and a pH-dependent release profile whereby low amounts of siRNA was released under acidic vaginal conditions (vaginal fluid simulant; VFS, pH 4.2) (6.0 ± 0.4% released over 15 days) but significantly higher amounts of siRNA was released under neutral pH conditions (phosphate buffered saline; PBS, pH 7.4) (22.9 ± 0.4% released over 15 days). The CCR5-Nef-specific siRNA NP efficiently knocked down CCR5 and Nef protein expression by 43% and 63%, respectively, reactivated Nef-blocked autophagy and inhibited the replication of HIV in vitro (71.8% reduction in p24 expression). After being formulated into a gel dosage form, siRNA NP could be readily released from the gel, penetrate the vaginal epithelial layer, get taken up into the target cells and knockdown Nef and CCR5 without causing cytotoxicity in a vaginal mucosal co-culture model. Functionalization of siRNA NP with anti-CD4 antibody and loaded into a 0.5% HEC gel improved vaginal distribution and uptake of siRNA in a mouse model with distribution of siRNA restricted to the reproductive tract without any unwanted systemic uptake. The 0.5% HEC gel loaded with siRNA NP-(m)CD4 significantly downregulated approximately 40% of CCR5 protein in the lower vagina and 36% of CCR5 protein in the upper vaginal and cervical region. In contrast, 0.5% HEC gel loaded with siRNA NP-IgG did not result in significant gene knockdown.

Maintaining vulvar, vaginal and perineal health: Clinical considerations.

Knowledge of female genital anatomy and physiology is often inadequate or incorrect among women. Precise patient-physician conversations can be inhibited by a reluctance or inability to speak accurately about the vulva and vagina, with the terms often being used interchangeably. There is a paucity of scientific evidence and clinical guidelines to support women and physicians in ensuring best practices in feminine hygiene. In this review, the unmet needs in the field are highlighted. Evidence is provided for the complex array of physiological and pathological systems, mechanisms and behaviours that either protect or, if inappropriate, predispose the vulva and vagina to infections, irritation or other conditions. The need for attention to perineal health is recommended, given the interdependence of perineal and vulvar microbiota and the risk of colonic pathogens reaching the vulva and the vagina. Differences in feminine hygiene practices can vary widely across the world and among varying age groups, and suboptimal habits (such as vaginal douching or the use of certain cleansers) can be associated with increased risks of vulvar and vaginal conditions. Critical areas for discussion when advising women on their intimate health include: advice surrounding aesthetic vulvar cosmetic trends (such as depilation and genital cosmetic surgery), bowel health and habits, and protection against sexually transmitted infections. Routine, once-daily (maximum twice-daily) washing of the vulva with a pH-balanced, mild cleanser is optimal, ideally soon after bowel voiding, when feasible. Due to the finely balanced ecosystems of the vulva, the vagina and the perineal area, a scientific and clinical perspective is essential when determining the most appropriate vulvar cleansers based on their components. Correct intimate care may contribute to improved genital and sexual health and overall well-being. An increased awareness of correct practices will empower women to be the advocates of their own intimate health.

Comparative Analysis of Pelvic Floor Muscle Damage Postpartum: Vaginal Delivery vs. Cesarean Section

Background. Evaluation of pelvic floor muscle (PFM) strength damage across different delivery modes, providing insights into potential preventive measures for pelvic floor dysfunctions (PFDs) in the early postpartum period. Aim. Compare the differences in PFM strength and endurance between full‐term cesarean section (CS) and vaginal delivery (VD) in the early postpartum period of primiparous women. Methods. The assessment included stress urinary incontinence (SUI), pelvic organ prolapse (POP), and pelvic floor electromyography (PFE). Muscle fiber strength was categorized into four modes at a threshold level of 3: I < 3 II < 3, I < 3 II > 3; I > 3 II < 3, I > 3 II > 3. Multinomial logistic regression was employed for CS and VD, and a sensitivity analysis was conducted using level 2 as the threshold. Outcomes. When muscle fiber strength was categorized into four modes at a threshold level of 3, Type I, and Type II fiber muscle endurance (FME) are differences between the CS and VD groups. Results. The CS and VD groups differed significantly in SUI and anterior and posterior vaginal wall conditions. MDVP was below the normal range in both groups, and MDVP, PFM strength, and PFM endurance did not differ significantly (P > 0.05). Logistic regression results indicated that higher MDVP, Type I, and Type II FME were protective factors when I < 3 in the VD group. However, I < 3‐II > 3, higher MDVP, and Type I FME were protective factors (OR: 0.339, 95% CI: 0.223, 0.516) in the CS group. Clinical Implications. The study introduces a nuanced understanding of the impact of different delivery modes on PFM, contributing valuable insights for clinical prevention and treatment strategies in the early postpartum period. Strengths and Limitations. Muscle fiber strength was categorized into four modes and further sensitivity analysis was conducted. This study only conducted a correlation analysis of outcome variables without considering intervenable variables. Conclusions. The VD group had a higher incidence of pelvic floor dysfunction in the early postpartum period than the CS group. Both groups experienced a decline in PFM function without significant differences. CS was primarily associated with Type I muscle fiber damage, while VD was related to both Type I and II muscle fiber damage. Improving PFM endurance is beneficial for muscle strength recovery.

Light and energy-based therapeutics for genitourinary applications: Consensus on protocols and best practices.

Lasers and energy-based technologies have been developed for genitourinary applications over the past several decades. This consensus article aims to categorize the published articles and clinical trial data that culminated in protocol development of technology for genitourinary applications, and to develop consistent parameters in future clinical trials. The published articles and clinical trials data on lasers and energy-based devices applied to genitourinary conditions were categorized according to device and condition and consensus developed on protocols and parameters. The devices in genitourinary applications were classified as fractional lasers, radiofrequency and high-intensity focused electromagnetic field therapy. The consensus of the protocols and parameters based upon the published clinical trials of their application to the vaginal and urologic conditions associated with genitourinary syndrome of menopause was developed and organized according to device and condition. The status of FDA clearances and future pathways are discussed. This consensus article categorizes and presents the protocols and practices for the main classes of lasers and energy-based devices for genitourinary applications in future clinical trials.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

Effect of Vapor-Phase Oregano Essential Oil on Resistant Candida Species Biofilms: Mechanisms of Action.

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases. The increasing incidence of drug-resistant Candida strains and the limited therapeutic options make the discovery of effective alternative therapies fundamental. Essential oils (EOs) have been suggested as a promising alternative, and interestingly, vapor-phase essential oils (VP-EOs) present more advantages than their direct application. Thus, this study aims to evaluate the effect of oregano VP-EO (VP-OEO) on biofilms of antifungal-resistant vaginal isolates of Candida species (Candida albicans and Candida glabrata) and determine its mode of action. CFU, membrane integrity, and metabolic activity were evaluated. Furthermore, a reconstituted vaginal epithelium was used to mimic vaginal conditions and evaluate the effect of VP-OEO on Candida species infection, analyzed by DNA quantification, microscopy, and lactate dehydrogenase activity. The results revealed high VP-OEO antifungal activity. There was a significant reduction (>4 log CFU) in Candida species biofilms. Furthermore, the results show that the mechanisms of action of VP-OEO are related to membrane integrity and metabolic activity. The epithelium model confirms the effectiveness of VP-OEO. This study suggests that VP-EO can be considered a first approach for the development of an alternative form of VVC treatment. IMPORTANCE This work presents a new approach to the application of essential oils, exposure to the vapor phase, which can be considered a first approach for the development of a complementary or alternative form of vulvovaginal candidiasis (VVC) treatment. VVC is a significant infection caused by Candida species and remains a common disease that affects millions of women every year. The great difficulty in treating VVC and the extremely limited effective therapeutic options make the development of alternative treatments crucial. In this scope, this study aims to contribute to the development of effective, inexpensive, and nontoxic strategies for the prevention and treatment of this infectious disease, based on natural products. Moreover, this new approach has several advantages for women, such as lower costs, easy access, an easier mode of application, avoidance of skin contact, and, therefore, fewer negative impacts on women's health.

Simulated vaginal fluid: Candida resistant strains' biofilm characterization and vapor phase of essential oil effect.

Vulvovaginal candidiasis is a disease that affects millions of women worldwide. Oral formulations, topical creams or ointments are the conventional dosage forms, with an increase in drug administration through vaginal via. The use of simulated biological fluids (e.g. vaginal fluid) in the evaluation of antifungal therapies may better mimic the real biological environments and therefore provide a better understanding of the behavior of the antifungal. The main objective of this work was to compare planktonic growth and biofilm formation of Candida species, on common growth medium, Sabouraud Dextrose Broth (SDB) and on vaginal simulation conditions, Simulated Vaginal Fluid (SVF), through the optical density determination, colony-forming units and scanning electron microscopy. In addition, under the same conditions this study also evaluated the ability of vapor phase of oregano and white thyme essential oils (VP-EOs), potential alternative treatment, to inhibit biofilm formation and to destroy mature biofilms of vaginal isolates, through the colony-forming units determination. Candida isolates maintained the same biofilm formation capacity and morphology in both media (SVF and SDB). Furthermore, the results obtained in this work related with VP-EOs effect agree with results acquired, previously, with SDB. This means that the effect of VP-EOs is not affected by the SVF medium, and that this fluid allows the dissolution of the volatile and bioactive compounds. These results can predict the in vivo behavior, suggesting a potential effective application of VP-EOs as prophylactic or therapeutic treatment for biofilm-related vulvovaginal candidiasis.

CO2 Surgical Laser for Treatment of Stress Urinary Incontinence in Women: A Randomized Controlled Trial

ABSTRACT The common condition of stress urinary incontinence (SUI) has a reported prevalence of 10% to 39% in adult women in most studies. Although treatment of SUI via surgical means is an option, factors such as adverse effects of surgery and mesh-related risks lead many to seek alternative options. In overweight and obese patients, lifestyle changes for improving SUI symptoms entail mainly weight loss. Although pelvic floor muscle training (PFMT) can lead to improvements, further treatment is often necessary. Because of this, interest is high for developing effective nonsurgical treatments for SUI. One such possible treatment is vaginal laser therapy, which has been used as treatment for various vaginal conditions. The authors therefore carried out a randomized controlled trial (RCT) comparing CO2 laser with sham treatment for SUI. This multicenter, participant-blinded, sham-controlled, parallel-group, superiority RCT involved participants from 2 hospitals in Southeast Melbourne in the outpatient setting. Patients aged 18 to 80 years experiencing symptomatic and objective SUI and seeking conservative management participated. Women with prior surgery for SUI were excluded. A positive cough stress test with a comfortably full bladder and uroflow was used to determine objective SUI. Participants lacking positive cough stress test were still eligible for study inclusion with a positive pad weight test in the absence of urgency incontinence symptoms. Intervention took place using FemTouch delivery system in conjunction with the AcuScan 120 Microscanner and the AcuPulse CO2 laser system for fractional treatment. Laser energy was delivered via a standard foot pedal in a fractional manner. The sham treatment used identical methods and settings but used an inactive pedal, which only made mechanical clicks and no electronic beeps. A total of 3 treatments were administered to participants, 4 weeks apart, with incrementally greater density settings. The primary outcome of the study was subjective SUI (defined as positive answers to the inquiries: “Do you leak when you cough or sneeze?” or “Do you leak when physically active/exercising?”). Secondary outcomes were assessed via the Patient Global Impression of Improvement, and International Consultation on Incontinence Questionnaire–urinary incontinence change, International Consultation on Incontinence Questionnaire-overactive bladder, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, the Incontinence Impact Questionnaire–Short Form, and EQ-5D scores. In addition, adverse events (such as pain during the procedure as measured on a visual analog scale) and objective SUI were recorded. A sample size of 101 was chosen to provide 80% power to detect differences between groups for the primary outcome (even assuming a 10% rate of attrition). A total of 97 participants ultimately were treated. Randomization of participants occurred with equal probability to sham treatment or the CO2 laser using a computer-generated random sequence, which allocated participants to blocks of 4, 6, and 8. Unblinding of participants to their allocation occurred following the 3-month review. Participants had a mean age of 53 years and a mean body mass index of 26.1 kg/m2, and 90% were vaginally parous. Most participants had attempted PFMT either independently or under supervision. No detectable difference was found between the sham and active treatment arm in the primary outcome of leak with laughter or cough. Furthermore, there were no significant differences between groups with regard to any of the secondary, patient-reported outcomes of questionnaires. The authors tested the reliability of their masking by assessing whether patients could identify their allocation group. Between the 2 groups, 17 (54%) of the sham group and 15 (63%) of the active treatment group believed they received sham treatment. Adverse events were rare in both groups, with similar visual analog pain scores during treatment and only rare vaginal bleeding and urgency incontinence in both groups. Strengths of this study are several and include its blinded design and randomization methods. The primary outcome was focused on patient-reported outcomes. Responsive and validated questionnaires were utilized for assessment of secondary outcomes. Study limitations include a lack of blinding for investigators, which could have introduced an element of detection bias for SUI. In conclusion, no benefit was shown for 3 treatment sessions of the CO2 vaginal laser when compared with sham therapy. Additional trials with various laser modalities are necessary to determine whether this may produce varying results. Women considering CO2 vaginal laser therapy for SUI should be made aware of the lack of consistent high-quality evidence in support of this treatment.

The Role of Probiotics in Preventing Recurrent Bacterial Vaginosis and Vulvovaginal Candidiasis: A Literature Review

Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) are the most common vaginal infections that cause vaginal discharge in women. An imbalance of the normal vaginal microbiota can make it easier for the vagina to become infected with bacteria and fungi. The recurrence rate for both diseases is 40–60%. Therefore, alternative therapies are needed to prevent the recurrence of these two diseases. Probiotics are believed to be able to maintain a normal microbiota balance in the vagina. This study aims to determine the role of probiotics in BV and VVC therapy, to prevent recurrence of these two diseases. A literature search was performed on two databases namely PubMed and Science Direct, using several keyword combinations to obtain relevant results. There were 12 studies that met the inclusion and exclusion criteria. There are six studies explaining the role of probiotics in BV and VVC, respectively. The use of probiotics intravaginally or orally can significantly reduce the recurrence rate of these two diseases, restore normal vaginal conditions in BV as well as improve clinical symptoms in VVC. The combination of antibiotics and probiotics can increase the effectiveness of the therapy.

Analysis of Maternal and Infant Outcomes and Related Factors of Vaginal Delivery of Second Pregnancy after Cesarean Section.

Objective To explore the clinical effect of different delivery methods and the safety of vaginal delivery of second pregnancy after cesarean section and analyze the related factors. Methods A total of 738 eligible pregnant women who underwent cesarean section from September 2018 to August 2020 were randomly selected from our hospital. Among them, 527 pregnant women successfully delivered vaginally were selected as the observation group, and 211 pregnant women who failed vaginal delivery were selected as the control group. To analyze the factors that influence the success of vaginal delivery of second pregnancy after cesarean section and compare the outcomes of mother and infant in two groups. Results There was no significant difference in age, prenatal body mass index (BMI), and thickness of lower uterine segment between the two groups (P > 0.05). There were significant differences in fetal head orientation, fetal abdominal circumference, fetal biparietal diameter, uterine height, premature rupture of membranes, Bishop score, and epidural anesthesia during labor between the two groups (P < 0.05). Multivariate logistic regression analysis showed that fetal abdominal circumference, fetal head orientation, Bishop score, and epidural anesthesia during labor were independent factors affecting the success of VBAC (P < 0.05). There was no significant difference in the incidence of uterine rupture between the two groups (P > 0.05). The amount of postpartum hemorrhage in the observation group was significantly lower than that in the control group (P < 0.05). There was no significant difference in Apgar score, asphyxia rate, and hospitalization rate between the two groups (P > 0.05). There was no significant difference in the incidence of complications between the two groups (P > 0.05). Conclusion There are many factors that influence the success of vaginal delivery after cesarean section. Through prenatal comprehensive evaluation of vaginal delivery conditions, we can guide the parturient to choose a reasonable mode of delivery, reduce the incidence of complications, and improve the outcome of mother and baby.

Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue.

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application. Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model. Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice. Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.

Postgraduate Training in Pediatric and Adolescent Gynecology: Trainees' Perspectives

The purpose of this study was to evaluate resident trainees' perspectives on the pediatric and adolescent gynecology (PAG) training in obstetrics and gynecology training programs in Europe. This study was a cross-sectional survey using an online questionnaire, on the basis of the PAG training in obstetrics and gynecology section of the European Board & College of Obstetrics and Gynaecology Project of Achieving Consensus in Training curriculum. We aimed to survey the national programs in 35 European Network of Trainees in Obstetrics and Gynaecology (ENTOG) member countries. Taking part in the survey was voluntary. The questionnaire was shared on the ENTOG online platforms. Ninety obstetrics and gynecology trainees in 33 of 35 countries responded to our questionnaire. Of the 35 ENTOG member countries, 33 participated in the survey, and a total of 90 responses were collected, giving a response rate of 9% of all European trainees and representing 94% of the member countries. Only 27% of trainees reported having a PAG rotation during their training program, and a PAG elective was only available to 34% of the trainees. Forty-one percent reported that PAG training was not included in their curriculum (no official rotations or lectures planned). Despite the lack of formal training, 72% of trainees felt able to diagnose and manage prepubertal vaginal bleeding and adnexal masses in children and adolescents by the end of their training. Most (58%) also confirmed that they could determine indications for treatment of vulval, vaginal, perineal, and rectal conditions. However, despite scoring positively for the management and counseling of subjects that often overlap with adult patients, such as "contraception in adolescents with health problems," "acute abdominal pain," "menstrual abnormalities," and "vaginal discharge," the study revealed poorer scores when the trainees were asked about more specific PAG topics such as "premature puberty" and "developmental disorders of the genital tract." Most core training programs across Europe do not include formal PAG training, and trainees reported a need to improve the provision of core PAG training in Europe.

Vaginal non-ablative Er:YAG laser sexual dysfunction therapy in women with interstitial cystitis/bladder pain syndrome: A Case Series

ABSTRACT Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating disease characterized by urinary frequency, urgency, and pelvic pain. Different studies have evaluated sexual well-being and e female sexual dysfunction (FSD) in IC/BPS patients. FSD in women with IC/BPS consists of dyspareunia, altered sexual desire, reduced orgasm frequency and vaginal insufficient lubrication. Recently, it has been repeatedly demonstrated that vaginal non-ablative erbium YAG laser (VEL) therapy can improve objective and subjective symptoms in different conditions. In our experience, VEL was very effective in various indications (stress urinary incontinence, mixed urinary incontinence, overactive bladder, genitourinary syndrome of menopause and FSD). In this study we evaluated the effects of VEL on FSD in women suffering from IC/BPS. Materials and methods This is case series study in which women with IC/BPS were also reporting FSD. The patients were treated with VEL with protocol in which the laser firstly irradiated the whole anterior vaginal wall and then also the entire vaginal canal. Local topical anesthesia was applied to the vagina before the laser irradiation. The therapy consisted in 1 treatment every 30 days, for 3 months. For the assessment of treatment effects we evaluated the personal history including: age at onset of IC/BPS and FSD, type of IC/BPS, bladder IC/BPS surgeries, the numeric rating scale-11 (NRS-11), O'Leary-Sant interstitial cystitis symptom and problem indexes (ICSI and ICPI), functional bladder capacity, daily urinary frequency, female sexual function index (FSFI) and vaginal health index score (VHIS). Follow-up was done 6 months from the first laser session. Potential adverse effects were observed at every visit as well as at 6 months follow-up. Results Six women were treated with the three sessions of VEL and followed for 6 months. The FSFI and VHIS significantly improved in all patients. The NRS-11 scores and the part of pain question of ICSI and ICPI improved as well. The bladder capacity and daily urinary frequency showed a marginal improvement. The therapy effects lasted for 6 months from the first treatment. All observed adverse effects were mild and transient. Conclusion Women suffering from IC/BPS have often impaired sexual life. Our data suggest that, besides being safe, VEL treatment can improve sexual life reducing also pain symptoms in IC/BPS patients. Further larger studies are needed in order to ascertain the relations between vaginal conditions and bladder pain, evaluating the possible role of VEL as a new approach for the treatment of FSD in IC/BPS women. Disclosure Work supported by industry: no.

Experience in the clinical administration of ferrous sulfate for treating post-covid anemia in puerperas

Introduction. According to domestic and foreign authors, most women have a greater or lesser level of iron deficiency by the end of pregnancy and deplete their depot iron reserves, and anaemia develops by the time of delivery. Erythrocyte destruction occurs in presence of acute inflammation, including that caused by COVID-19, which leads to a chaotic distribution of iron within tissues and a pronounced loss of its reserves and aggravation of the existing deficiency. Due to overlapping changes with underlying novel coronavirus infection, iron deficiency creates favourable conditions for the development of infectious and inflammatory complications in the postpartum period by the time of delivery.Aim. To assess the features of the postpartum period and hematological status in puerperas with post-COVID anemia, who receive the combination therapy including an anti-anemic ferrous iron drug.Materials and methods. The prospective study included 30 puerperas (treatment group) in the postpartum period, who had a coronavirus infection with a mild degree of IDA during the gestation period. Group 2 (comparison group) included 15 puerperas with mild IDA, who did not have a coronavirus infection during the gestation period. Group 3 (control group) included 15 conditionally healthy puerperas, who had no novel coronavirus infection and did not suffer from IDA during the gestation period.Results and discussion. The puerperas, who had COVID-19 in pregnancy, developed infectious and inflammatory diseases significantly more often in the postpartum period. Subinvolution of the uterus, postpartum endometritis and thyroiditis, disruption of perineal stitches and seromas (hematomas) of the suture after cesarean section, vaginal dysbiotic conditions occurred significantly more often in puerperas with IDA, who came through coronavirus infection, than in women from the comparison group and control group (SBI index, p &lt; 0.05).Conclusion. Women who had COVID-19 in pregnancy should be spinned off into a separate infectious risk group due to the possibility of postpartum complications and timely management of concomitant pathologies and appropriate treatment of IDA.

How were Lactobacillus species selected as single dominant species in the human vaginal microbiota? Coevolution of humans and Lactobacillus

The optimal microbiota in the vagina for women’s health is dominated by single species of Lactobacillus. However, the mechanism by which these species become dominant remains unknown. Therefore, understanding this mechanism is important to establish new treatments, such as probiotics, for vaginal dysbiosis-related conditions. To date, at least 5 hypotheses have been proposed to explain the vaginal dominance of Lactobacillus. However, these hypotheses do not address why a “single” species of Lactobacillus becomes dominant in the vaginal microbiota. First, we evaluated the effect of Lactobacillus culture supernatant on the biomass concentration of each different strain and species of Lactobacillus. The results indicated that the biomass concentrations were not significantly affected by the culture supernatant from other vaginal Lactobacillus species. Then, we discussed host factors that select the vaginal Lactobacillus species and the antagonism of vaginal bacteria. We also assess the mechanism of coevolution of humans and Lactobacillus. Here, we present the hypothesis that host factors such as antimicrobial peptides and proteins (AMPs) and immunoglobulins could play important roles in the selection of specific species of Lactobacillus in the vagina.

Lactobacilli reduce recurrences of vaginal candidiasis inpregnant women: a randomized, double-blind, placebo-controlled study.

The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n=39; placebo, n=39) and the potential benefits on quality of life. The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P=0·023) and discharge (P=0·011) starting week-4 and continued after week-8 (P<0·05), accompanied by reduced symptoms for burning after week-8 (P=0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P=0·010) and continued after week-8 (P=0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P=0·012) and continued after week-8 (P=0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P<0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P=0·010) and week-8 (P=0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation. Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC. The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.