Search Results (18)

Background/Objectives: Unexplained infertility is a worldwide problem affecting a significant proportion of couples of reproductive age. Recent studies suggest that alterations in the vaginal microbiota are related to female infertility, while supplementation with some probiotic strains has been shown to improve pregnancy rates in couples experiencing this problem. This study aimed to evaluate the impact of oral administration of Ligilactobacillus salivarius CECT5713 on pregnancy success rates in couples with unexplained infertility prior to in vitro fertilization (IVF). Methods: Seventy couples were randomized to receive either a placebo or a probiotic intervention (one capsule per day containing an excipient only or 3 × 10⁹ viable cells of L. salivarius CECT5713 plus an excipient, respectively); 57 couples completed the study. Baseline data on demographics, health status (including gynecological and reproductive history), and lifestyle habits were collected. Vaginal swabs and semen samples were obtained from each couple before the intervention and immediately prior to IVF or upon confirmed pregnancy and were analyzed for microbiological (using both culture-dependent and -independent methods) and immunological profiles. Results: Oral administration of L. salivarius CECT5713 in couples with unexplained infertility scheduled for IVF resulted in a significantly higher pregnancy success rate (48.1%) compared to the placebo group (20.0%) (one-tailed Chi-square test; p < 0.024). The probiotic intervention improved both vaginal and semen immunological profiles, with no substantial changes observed in their microbial composition. Conclusions: These preliminary findings support the potential of L. salivarius CECT5713 supplementation to enhance fertility outcomes in couples with unexplained infertility. Full article

Lactobacillus spp. and other beneficial bacteria are predominant in the vaginal microbiota and represent an opportunity to correct dysbiosis if administered intravaginally. Since no commercial formulations are available, developing magistral formulations is an option, provided that they ensure viability and therapeutic efficacy. To evaluate their stability and culturability, four magistral formulations containing 10⁹ microorganisms were tested: vaginal capsules, vaginal ointment, gelatinous ovules, and waxy ovules. Certified strains of L. crispatus, L. johnsonii, L. gasseri, Limosilactobacillus reuteri, and Lacticaseibacillus rhamnosus, as well as a combination of the five, were used. The formulations were tested for pharmaco-technical stability using average weight and disintegration tests, as well as evaluation organoleptic. In addition, microbial recovery was evaluated by counting Colony-Forming Units (CFUs). All forms, except the gelatinous ovules, allowed microbial recovery at concentrations from 10⁷ to 10⁹ CFUs, ensuring stability for 60 days. The recovery varied depending on the strains and dosage forms employed, with the most favorable outcomes for vaginal capsules. This highlights the need for standardized strains and excipients in magistral formulations. Further studies are needed to evaluate the viability of other strains of different excipients, vehicles, or different storage; however, capsules have demonstrated efficacy and are an excellent candidate for vaginal use formulations of Lactobacillus spp. Full article

Objective: During pregnancy, vulvovaginal infections (VVIs), including abnormal vaginal flora (AVF), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC), are associated with serious complications and discomfort. We aimed to elucidate the effectiveness of oral probiotics in secondary prevention of VVIs in pregnant women. Study design: A multicenter prospective randomized, double-blind, placebo-controlled trial was conducted at three medical centers between 2016 and 2021. Women who complained of vaginal symptoms with positive smear for AVF/BV and/or candida were treated with antibiotics or an antimycotic agent, respectively. After confirmation of VVI eradiation by repeated vaginal smear, the women were divided into a research group, receiving two capsules/day of oral probiotic formula containing Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus (L.) acidophilus, L. paracasei, L. rhamnosus and Streptococcus thermophilus (>6 × 10⁹ CFU/capsule), and a control group, receiving a placebo (two capsules/day) until delivery. At least once a month or following complaints, a vaginal smear was taken to assess vaginal microbiota. If VVIs were found, they were treated with antibiotics/antimycotics, and eradication was assessed by a repeated vaginal smear. Lactobacilli vaginal colonization, including the specific strains from the probiotic capsules, were detected using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF-MS). The primary outcome was the rate of women who developed VVI during the study period until delivery. Results: Twenty-three and twenty-four women were analyzed in the probiotic and placebo cohorts, respectively. There was no difference in the rate of any VVI between the probiotic and placebo cohorts (16 (67%) versus 11 (48%), respectively; p = 0.19), time until first infection or pregnancy outcomes. The lactobacilli strains that colonized the vagina were similar at baseline and following probiotic or placebo administration. No woman was detected with vaginal colonization of the strains from the capsule, although the probiotics were taken for about 4 months. Conclusions: The oral probiotic product tested in this study did not reduce the recurrence rate of VVIs in pregnant women following eradication. Full article

Background/Objective: This study aimed to investigate the efficacy of oral probiotic supplementation in preventing vulvovaginal infections (VVIs) in pregnant women, specifically focusing on abnormal vaginal flora (AVF), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC). Methods: A multicenter-prospective-randomized, double-blind, placebo-controlled trial was conducted during 2016–2019. Women with normal vaginal flora (Nugent score < 4 and no candida) were divided into a research group, receiving 2 capsules/day of oral probiotic formula containing Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus, or a control group, receiving a placebo until delivery. Once a month and following complaints, a vaginal smear was taken to assess vaginal flora. Vaginal colonization with the specific lactobacilli from the probiotic capsules was detected using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The primary outcome was the rate of women who developed VVI. Results: Forty-nine and fifty-one women were analyzed in the probiotic and placebo cohorts, respectively. There was no difference in the rate of VVI between probiotic and placebo groups (14 (29%) versus 14 (27%), respectively; p = 0.80). No woman had vaginal colonization with lactobacilli from the probiotic capsule. Conclusions: The tested oral probiotic product did not reduce the rate of VVI in pregnant women with normal vaginal flora. Full article

Background/Objectives: the vaginal microbiota is known to confer protection in the genital ecosystem, due to the predominance of different Lactobacillus species, playing a crucial role in women’s health; alterations in the composition of the microbial communities in the vagina can be associated with the development of bacterial vaginosis (BV). Current therapy for BV involves oral or intravaginal administration of metronidazole or clindamycin, albeit the high recurrence rates suggest a need for alternative therapeutic tools, such as probiotics. Herein, the diversity and composition of vaginal microbiota in women with asymptomatic BV was investigated before and after the oral administration of a multi-strain probiotic formulation. Methods: a prospective observational pilot study with pre–post design was carried out from 1 June 2022, to 31 December 2022, on reproductive-age women with asymptomatic BV, as diagnosed via Nugent score, and matched healthy controls. The probiotic was administered to all study participants as acid-resistant oral capsules (twice daily), and a vaginal swab was collected at baseline and after 2 months of treatment, for the metagenomic analysis of 16s rDNA. Results: the diversity and richness of the vaginal microbiota in women with BV were significantly reduced after 2 months of supplementation with the oral probiotic, as evidenced by measures of α-diversity. Interestingly, some bacterial genera typically associated with dysbiosis, such as Megasphaera spp., were significantly decreased; whereas, at the same time, Lactobacillus spp. Doubled. Conclusions: our preliminary results suggest that the multi-strain oral probiotic is a beneficial treatment specifically targeting the dysbiotic vaginal microenvironment. Full article

Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 10⁹ CFU per capsule) in combination with bovine lactoferrin (Respecta^®). Each product was taken once daily for 90 days. Results: After 90 d of therapy with TIB+ Respecta^®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. Conclusions: This study provides evidence that the combination of TIB+ Respecta^® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting. Full article

Microparticles as a multicompartment drug delivery system are beneficial for poorly soluble drugs. Mucoadhesive polymers applied in microparticle technology prolong the contact of the drug with the mucosa surface enhancing drug bioavailability and extending drug activity. Sodium alginate (ALG) and hydroxypropyl methylcellulose (hypromellose, HPMC) are polymers of a natural or semi-synthetic origin, respectively. They are characterized by mucoadhesive properties and are applied in microparticle technology. Spray drying is a technology employed in microparticle preparation, consisting of the atomization of liquid in a stream of gas. In this study, the pharmaceutical properties of spray-dried ALG/HPMC microparticles with posaconazole were compared with the properties of physical mixtures of powders with equal qualitative and quantitative compositions. Posaconazole (POS) as a relatively novel antifungal was utilized as a model poorly water-soluble drug, and hard gelatin capsules were applied as a reservoir for designed formulations. A release study in 0.1 M HCl showed significantly prolonged POS release from microparticles compared to a mixture of powders. Such a relationship was not followed in simulated vaginal fluid (SVF). Microparticles were also characterized by stronger mucoadhesive properties, an increased swelling ratio, and prolonged residence time compared to physical mixtures of powders. The obtained results indicated that the pharmaceutical properties of hard gelatin capsules filled with microparticles were significantly different from hard gelatin capsules with mixtures of powders. Full article

A single-blind double-dummy randomized study was conducted in diagnosed patients (n = 66) to compare the efficacy of Linseeds (Linum usitatissimum L.), Psyllium (Plantago ovata Forssk.), and honey in uncomplicated pelvic inflammatory disease (uPID) with standard drugs using experimental and computational analysis. The pessary group received placebo capsules orally twice daily plus a per vaginum cotton pessary of powder from linseeds and psyllium seeds, each weighing 3 gm, with honey (5 mL) at bedtime. The standard group received 100 mg of doxycycline twice daily and 400 mg of metronidazole TID orally plus a placebo cotton pessary per vaginum at bedtime for 14 days. The primary outcomes were clinical features of uPID (vaginal discharge, lower abdominal pain (LAP), low backache (LBA), and pelvic tenderness. The secondary outcomes included leucocytes (WBCs) in vaginal discharge on saline microscopy and the SF-12 health questionnaire. In addition, we also classified both (pessary and standard) groups using machine learning models such as Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), and AdaBoost (AB). The pessary group showed a higher percentage reduction than the standard group in abnormal vaginal discharge (87.05% vs. 77.94%), Visual Analogue Scale (VAS)-LAP (80.57% vs. 77.09%), VAS-LBA (74.19% vs. 68.54%), McCormack pain scale (McPS) score for pelvic tenderness (75.39% vs. 67.81%), WBC count of vaginal discharge (87.09% vs. 83.41%) and improvement in SF-12 HRQoL score (94.25% vs. 86.81%). Additionally, our DT 5-fold model achieved the maximum accuracy (61.80%) in the classification. We propose that the pessary group is cost-effective, safer, and more effective as standard drugs for treating uPID and improving the HRQoL of women. Aucubin, Plantamajoside, Herbacetin, secoisolariciresinol diglucoside, Secoisolariciresinol Monoglucoside, and other various natural bioactive molecules of psyllium and linseeds have beneficial effects as they possess anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory properties. The anticipated research work is be a better alternative treatment for genital infections. Full article

A healthy vaginal microbiota is Lactobacillus-dominated. Several factors can interfere with the state of balance leading to dysbiosis, such as vaginal infections caused by bacteria and Candida species. The present single-arm, uncontrolled open-label study aimed to evaluate the ability of the SYNBIO^® probiotic combination, taken as an oral formulation, to contribute to vaginal health. Thirty pre-menopausal participants were included in the study. Participants were instructed for daily oral intake of SYNBIO^® probiotic capsules for 15 days. Vaginal swabs were collected at baseline (T0), 15 days after the start of the treatment (T1), and 7 days after the end of the treatment (T2). Amsel criteria, Nugent score, and vaginal pH were evaluated at each sampling time. In addition, the participants’ quality of life was assessed by the WHOQOL-BREF questionnaire. The administration of SYNBIO^® once daily for 15 days resulted in a substantial improvement in the vaginal flora in terms of an increase in lactobacilli and a decrease in enterococci, staphylococci, Gardnerella spp., and Candida spp. According to the results, statistically significant changes in leucorrhoea, itching, and vulvo-vaginal erythema/edema as well as a decrease in all the Amsel criteria were recorded. The oral consumption of SYNBIO^® demonstrated enhanced benefits for vaginal health. Full article

Since the appearance of the 3D printing in the 1980s it has revolutionized many research fields including the pharmaceutical industry. The main goal is to manufacture complex, personalized products in a low-cost manufacturing process on-demand. In the last few decades, 3D printing has attracted the attention of numerous research groups for the manufacturing of different drug delivery systems. Since the 2015 approval of the first 3D-printed drug product, the number of publications has multiplied. In our review, we focused on summarizing the evolution of the produced drug delivery systems in the last 20 years and especially in the last 5 years. The drug delivery systems are sub-grouped into tablets, capsules, orodispersible films, implants, transdermal delivery systems, microneedles, vaginal drug delivery systems, and micro- and nanoscale dosage forms. Our classification may provide guidance for researchers to more easily examine the publications and to find further research directions. Full article

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings. Full article

We previously reported on the effects of a lactobacilli probiotic (SynForU-HerCare; two capsules/day of 9.5 log CFU/capsule) in improving symptoms of vaginal irritation, discharge and burning in pregnant women with vaginal candidiasis upon administration for 8 weeks, accompanied by improved emotional and social quality of life parameters. Thus, the present study aimed to analyse vaginal microbiota and inflammatory changes in hope to better understand the improved clinical symptoms as observed previously. Patients in the probiotic group showed a decreased abundance of Candida glabrata after 8 weeks (p = 0.009) in the lower vaginal region, while patients in the placebo group did not show any changes over time. In the higher vaginal and cervicovaginal regions, patients in the placebo group showed a decreased abundance of Candida albicans only within 4 weeks (p < 0.05) but no changes in abundance of C. glabrata over time, while patients in the probiotic group showed a continuous decreased abundance of C. albicans and C. glabrata over 8 weeks (p < 0.05). Patients in the placebo group also had a decreased abundance of Lactobacillus crispatus over 4 weeks (p = 0.023) in the lower vaginal region and a decreased abundance of L. jensenii over 8 weeks in the cervicovaginal region (p = 0.001). Meanwhile, patients in the probiotic group had an increased abundance of L. crispatus in the lower vaginal region after 8 weeks (p = 0.012) and Lactobacillus jensenii over 4 weeks in the cervicovaginal region (p < 0.001). Inflammation may have occurred in both low and high vaginal regions, predominantly observed by the increased concentration of pro-inflammatory cytokine TNF-alpha in patients from the placebo group (p < 0.05), while the administration of probiotics has shortened the period of inflammation as observed from the reduced need for anti-inflammatory cytokine IL-4 and IL-10 over time (p < 0.05). Taken together, our present new data further support previous findings that probiotic SynForU-HerCare had a beneficial effect against vaginal candidiasis in pregnant women via modulation of the vaginal microbiota and microenvironment. Full article

Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an antifungal miconazole (MIC) vaginal capsule was found to increase the systemic exposure to DPV in women, suggesting a potential for drug-drug interactions. This study’s objective was to investigate the mechanism of DPV-MIC interactions using drug-metabolizing enzymes (DMEs; CYPs and UGTs) that are locally expressed in the female reproductive tract (FRT). In vitro studies were performed to evaluate the metabolism of DPV and its inhibition and induction potential with DMEs. In addition, the impact of MIC on DPV metabolism and the inhibitory potential of DPV with DMEs were studied. Our findings suggest that DPV is a substrate of CYP1A1 and CYP3A4 enzymes and that MIC significantly decreased the DPV metabolism by inhibiting these two enzymes. DPV demonstrated potent inhibition of CYP1A1 and moderate/weak inhibition of the six CYP and eight UGT enzymes evaluated. MIC showed potent/moderate inhibition of seven CYP enzymes and weak/no inhibition of eight UGT enzymes. The combination of DPV and MIC showed potent inhibition of seven CYP enzymes (1A1, 1A2, 1B1, 2B6, 2C8, 2C19, and 3A4) and four UGT enzymes (1A3, 1A6, 1A9, and 2B7). DPV was not an inducer of CYP1A2, CYP2B6, and CYP3A4 enzymes in primary human hepatocytes. Therefore, the increased systemic concentrations of DPV observed in IPM 028 were likely due to the reduced metabolism of DPV because of CYP1A1 and CYP3A4 enzymes inhibition by MIC in the FRT. Full article

How do body temperature and activity change before and after parturition in pregnant cows? Changes in body temperature such as ruminal, rectal, and vaginal temperature during the parturition have been reported, but there are no results of the simultaneous observation of body temperature and activity. The aim of this study was to simultaneously confirm changes in the ruminoreticular temperature and body activity before and after parturition using the ruminoreticular bio-capsule sensor every 1 h. The 55 pregnant cows were used for the experiment, the ruminoreticular bio-capsule sensor was inserted and stabilized, and the ruminoreticular temperature and body activity were measured. The ruminoreticular temperature was lower by 0.5° from −24 h to −3 h in parturition compared to 48 h before parturition and then recovered again after parturition. Body activity increased temporarily at the time of parturition and 12 h after parturition. Therefore, the ruminoreticular temperature and body activity before and after parturition was simultaneously confirmed in pregnant cows. Full article

The microencapsulation of the cannabidiol and its integration into the tampon can eliminate vaginal inflammation, which at the same time lead to relaxation of the abdominal muscles. The tampon, which contains the active substance cannabidiol (CBD), was developed as an advanced fibrous composite for sanitary application. The active substances were microencapsulated, and, as a carrier, liposomes micro/nano capsules were used. The CBD liposome formulation was analyzed by particle size, polydispersity index, zeta potential, and encapsulation efficiency. Particle size of the CBD liposome liquid formulation was increased by 19%, compared to the liposome liquid formulation and the encapsulation efficiency of CBD in liposome particles, which was 90%. The CBD liposome formulation was applied to cellulose material. The composition of the fibrous composite material was evaluated by Fourier transform infrared spectroscopy, the fiber morphology was analyzed by scanning electron spectroscopy, while the bioactive properties were assessed by antioxidant efficiency, antimicrobial properties, and desorption kinetics. CBD liposome functionalized tampons have both antioxidant and antimicrobial properties. Antimicrobial properties were more pronounced against Gram-positive bacteria. The desorption kinetics of the CBD liposome immobilized on the surface of the composite material was studied using antioxidant activity in the desorption bath. The prepared CBD liposome functionalized tampon additionally shows higher biodegradability compared to references. This high-quality, biodegradable sanitary material based on microencapsulated CBD components as a functional coating provides a platform for many different applications besides medical textiles, also for packaging, pharmaceuticals, paper and wood-based materials, etc. Full article