Vaginal Gel Research Articles

Support of the luteal phase in programs for transferring thawed embryos into the uterine cavity in patients with overweight and obesity

Introduction. Progesterone levels are a critical factor for embryo implantation in in vitro fertilization (IVF) programs, including thawed embryo transfer programs. Overweight/obese patients often have lower blood progesterone concentrations in the luteal phase during IVF cycles, which requires an individual approach to planning luteal support in this category of patients.Aim. To compare the pregnancy ratе and miscarriage rates up to 12 weeks of pregnancy in overweight/obese patients who underwent a program of transfer of thawed embryos into the uterine cavity, depending on the type and route of administration of gestagens.Materials and methods. The study included 76 overweight or obese patients. All patients were treated for infertility using a program for transferring a thawed embryo into the uterine cavity; luteal phase support was carried out either using micronized progesterone, identical to natural, – the drug Utrogestan in a daily dose of 800 mg intravaginally (40 patients), or combination therapy was prescribed – vaginal gel with progesterone 90 mg in combination with the synthetic progestin dydrogesterone in a daily dose of 30 mg, taken orally (36 patients).Results. The rates of pregnancy and miscarriage in the first trimester were comparable in both groups and did not depend on differences in luteal support.Conclusions. The formation of the luteal phase of the cycle in patients with overweight/obesity is equally effective using various forms of gestagens. The use of micronized progesterone may be preferable in patients with overweight/obesity in terms of the ability to monitor blood progesterone levels, a more favorable metabolic profile when used vaginally, and the possibility of switching to oral administration of the drug in the event of the development of adverse local events.

Effects of intravaginal curcumin gels combined with electroporation on vulvovaginal candidiasis

ObjectiveTo provide a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans. MethodsTemperature-sensitive in situ gels (ISG) were prepared using poloxamers 407 and 188 as matrices. The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29°C and gelation time of 2.5 min. ResultsElectroporation increased the transmucosal permeability of the model drug, doxorubicin and improved the antifungal effects of curcumin. In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG. In vivo pharmacodynamic experiments showed that, compared to the model group, curcumin ISG with electroporation inhibited the growth of Candida albicans, alleviated vaginal mucosal edema, and reduced the inflammatory response. ConclusionCurcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.

Additional Daily Intramuscular Progesterone for Luteal Phase Support does not Improve Live Birth Rates of Programmed Frozen-Thawed Embryo Transfer Cycles

This retrospective cohort study aims to investigate whether additional daily intramuscular progesterone (IMP) for luteal phase support improves live birth rates of programmed frozen-thawed embryo transfer (FET) cycles. The study was conducted at a tertiary level university hospital assisted reproductive technology (ART) center between January 2014 and Jan 2021. Six hundred four infertile patients with single-day 5-6 frozen-thawed blastocyst embryo transfer were enrolled in the study. All patients received either 8% micronized vaginal gel or vaginal progesterone capsules for luteal phase support. Intramuscular progesterone was added to vaginal progesterone depending on the in vitro fertilization (IVF) specialist’s choice. Luteal phase support (LPS) was started 6 days before transfer in frozen-thawed cycles and continued until the end of the first trimester. Cycles were compared depending on vaginal progesterone types (8% gel vs. capsule) and the presence of intramuscular progesterone. The primary outcome was the live birth rate. A total of 604 FET cycles were enrolled. Using 8% micronized progesterone or progesterone capsules did not change the live birth rates (24% vs. 25.9%). As the main result, intramuscular progesterone support with vaginal progesterone compared with only vaginal progesterone did not improve the live birth results (22% vs. 24%). In conclusion, this study demonstrated that routine IMP progesterone given in combination with vaginal progesterone does not improve ART outcomes. This combination may be beneficial in a selective population with a monitored luteal phase. Using any form of vaginal progesterone alone is adequate for LPS.

Effect of a multi-ingredient coriolus-versicolor-based vaginal gel in women with HPV-dependent cervical lesions: the PAPILOBS real-life prospective study

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women _ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study’s duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild–moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.

Efficacy and safety of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause: A randomized double-blind placebo-controlled trial

ObjectivesThis study evaluated the efficacy of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause. Study designRandomized, double-blind, placebo-controlled, multicenter clinical trial conducted across 28 Spanish sites involving specialists in gynecology, urology, and primary care. A total of 108 postmenopausal women were randomly assigned in a 1:1 ratio to receive 1 g of vaginal gel with 50 micrograms of estriol or an identical moisturizing vaginal gel without estriol. Main outcome measuresThe primary outcome was the number of episodes of urinary tract infection by the end of the 24-week treatment. Secondary measures encompassed percentage of patients without recurrence, time to first recurrence, use of antibiotic treatment, vaginal pH, safety, and tolerability, among others. ResultsThe incidence rate of urinary tract infections (new cases per 100 women-year) was 26 % lower in the group that received estriol vs. the group that received placebo (32.34 vs. 43.76 (RR = 0.74) p < 0.001). The frequency of urinary tract infections fell during treatment in all patients in the estriol group. Favorable pH changes from baseline were observed in the estriol arm at all follow-up visits. ConclusionsUltra-low-dose 0.005 % estriol vaginal gel is safe and effective in preventing recurrent urinary tract infections in postmenopausal women with genitourinary syndrome of menopause, reducing the incidence and potentially decreasing the susceptibility to urogenital infections by improving vaginal pH.Study registration N°: 2018-001481-42. Date of registration: 09-04-2018.

Effects of progesterone administered to maternal rats during the teratogenesis-sensitive period through different routes on neurobehavior and gut microbiota in offspring

Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring. Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group; Group 2, the IG group, in which utrogestan was administered via intragastric gavage; Group 3, the IM group, in which P4 was administered via intramuscular injection; and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis. Results: No significant alterations in fertility outcomes were observed through three P4 administration routes—intragastric gavage, intramuscular injection, and vaginal administration—in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatment via the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereas Olivella appeared exclusively in the control group rather than in the P4 treatment groups. Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.

Formulation Development of Mucoadhesive Vaginal Gel of Secnidazole and Voriconazole.

Purpose: Over the preceding decades, developing conventional drug delivery in to modified form has acquired importance in the pharmaceutical industry. Vaginal drug delivery system offers localized drug administration of drug and also avoids unwanted side effects of oral drug delivery. Vaginal drug delivery system has significant role in medical practice. Even though VDDS has a lot of advantages over the other routes of administration. The goal of developing the Mucoadhesive Vaginal Gel was to achieve the synergistic effect of voriconazole and secnidazole in the treatment of bacterial and fungal vaginal infections. Method: Mucoadhesive antimicrobial vaginal gel was optimised using Design expert software using Carbopol 934, HPMC K4M polymers. Result: Formulation was evaluated for various rheological parameters ,antimicrobial activity, invitro drug release and stability study. The spreadability and pH was found to be 5.5 to 7.4 cm and 4.12. Its compatible with vaginal pH. The selected optimized F8 formulation is the best formulation and the drug ratio is 2:1. and optimum gel viscosity is 1874 cps. antimicrobial study revealed that faster drug release of test formulation was compared to marketed product. It indicates as inhibition zone. Conclusion: The combination of drugs can serves as better option for treating vaginitis, compared to single drug formulation. Mucoadesion increases contact time of drug with affected area which rendered formulation more effective.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p &gt; 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

Biocompatibility of a Novel Prebiotic Vaginal Gel for Treating the Underlying Conditions of Vaginal Dysbiosis and Inflammation That Facilitate Cervical Cancer Formation and Progression

Biocompatibility of a Novel Prebiotic Vaginal Gel for Treating the Underlying Conditions of Vaginal Dysbiosis and Inflammation That Facilitate Cervical Cancer Formation and Progression

Short and long-term effect of polycarbophil vaginal gel on vaginal atrophy of peri- and post-menopausal women. The TRIPLE study

ObjectivesThis TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women. Materials and methodsSexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days. ResultsWomen in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of −24.4 ± 3.6, and −52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of −18.6 ± 4.4 and −47.8 ± 3.2, VAS of pain decreased (p < 0.001) of −26.2 ± 4.3 and −55.6 ± 3.1 and the GSS decreased (p < 0.001) of −3.9 ± 0.3, and −4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of –53.6 ± 1.9 (p < 0.001) VAS of irritation of −42.6 ± 1.4 (p < 0.001) VAS of pain of −46.7 ± 2.3 (p < 0.001) and the GSS of −6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported. ConclusionsIn peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy.

Efficacy of Hormonal and Non-hormonal Vaginal Gel Preparations on Female Sexual Satisfaction Index in Postmenopausal Women with Sexual Dysfunction Syndrome

Efficacy of Hormonal and Non-hormonal Vaginal Gel Preparations on Female Sexual Satisfaction Index in Postmenopausal Women with Sexual Dysfunction Syndrome

Response to Antibiotic Treatment of Bacterial Vaginosis Predicts the Effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the Prevention of Recurrent Disease.

Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment. A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks. At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35-0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47-2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure. LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.

Incorporation of efavirenz inclusion complex In Dissolvable Microneedle for enhanced effectiveness of intravaginal drug delivery: A proof of concept study

Efavirenz (EFV) is one of the first line treatments of HIV infection. EFV is one of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that can inhibit the responsible of reverse transcriptase enzyme for HIV replication. In oral administration, EFV exhibits low bioavailability (30–56 %) problem owing to its poor solubility (0.9 μg/mL). In this research, the poor solubility was overcome by formulating EFV as a complex inclusion (IC)with β-cyclodextrin (β-CD). Furthermore, considering the benefits of vaginal delivery, IC was further incorporated into dissolving microneedle systems (DMN) using polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) as biocompatible and biodegradable polymes. The results showed that EFV successfully formed IC by the change of the molecular shape with β-CD polymer, confirmed by FTIR and XRD. Importantly, the results showed that the formulation did not cause lysis and irritation on erythrocytes and blood vessels, showing the safety of this approach. Following its incorporation into DMN, IC-DMN could permeate the skin ex vivo as 78.70 ± 14.22 μg/cm3, which was about 3-times higher compared to DMN containing pure EFV and patch control. The in vivo pharmacokinetic study showed that the maximum plasma concentration of IC-DMN was 13.74 ± 2.48 μg/cm3, EFV-oral 6.27 ± 1,13 μg/cm3, vaginal gel 14.83 ± 3.65 μg/cm3. AUC values for each treatment was 147.33 ± 26.62 h μg/mL, 22.33 ± 4.03 h μg/mL, 63.33 ± 11.44 h μg/mL, respectively, indicating that the purpose of this study which was to increase the bioavailability of EFV was succefully achieved. Therefore, this combibation approach could be new alternative to HIV treatment using EFV in woman.

Methods of mathematical planning of the experiment and their use in the development of the composition of the ointment with essential oil thymus vulgaris l. For vaginal application

One of the most important pharmaceutical factors is excipients, their nature and quantity, which increase the pharmacological activity and safety of APIs by creating dosage forms that are optimal in composition, properties, and type, and/or by changing the chemical modification of the molecule responsible for the pharmacological effect of the active substance. Variability or variation in the number of excipients and the use of different excipients with the same intended functionality can complicate the release rate and bioavailability of drugs. The use of mathematical methods at the stage of the experiment planning reduces the total number of experiments and at the same time provides reliable results. Aim. To study the most used types of mathematical planning of the experiment, and select the most acceptable model for developing the optimal composition of a vaginal ointment with the thyme (Thymus vulgaris L.) essential oil. Results and discussions. To develop the optimal composition of the ointment, 10 bases containing various excipients (factor A) and 6 excipients as an emulsifier (factor B) were used. The concentration of the thyme essential oil was 5 % in all samples. The degree of thymol release in the in vitro study using the equilibrium dialysis method was chosen as the criterion for choosing the optimal composition. The selection of excipients for the development of a soft dosage form was carried out using the method of the a priori ranking since both bases and emulsifiers were selected as the most widely used in the pharmaceutical technology, with known characteristics, safety profile, application experience. Conclusions. The degree of influence of each factor has been determined, and the series of Duncan’s test have been constructed for each factor – by factor a: а3 &gt; а5 &gt; а4 &gt; а6 &gt; а2 &gt; а8 &gt; а7 &gt; а10 &gt; а9&gt; а1, and by factor b: b2 &gt; b3 &gt; b5 &gt; b4 &gt; b6 &gt; b1. Based on the mathematical planning of the experiment, an ointment base and an emulsifier for developing the composition of a vaginal gel with the thyme oil have been determine.

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180mg/d. The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). 30mg/d oral dydrogesterone and 180mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis

The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2=0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2=0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2=0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. None.

Determination of multipurpose prevention technology choice for contraception and HIV/STI prevention: A survey of sexually active women in Nigeria

Objectives: Interest in human immunodeficiency virus (HIV) prophylaxis in the context of multiple sexual and reproductive health risks women face suggests a place for multipurpose prevention techniques (MPTs), which act by combining contraception and pre-exposure prophylaxis against HIV into one unified delivery method. At present, condoms are a readily available form of MPTs. The study aims to determine the sexual characteristics of women in Nigeria and assess factors associated with MPT acceptance in the identified population. Materials and Methods: An online cross-sectional survey was conducted using the data collection tool Google Forms®. The survey was distributed to the prospective respondents using the snowballing technique through an instant messaging application to ensure proper circulation among the geopolitical zones in Nigeria. Interest in MPT’s was evaluated using descriptive analysis. Specifically, personal and product attributes were evaluated descriptively (frequency and response rating) and with inferential statistics (logistic regression and model validation). Results: More than one-half (57%) of the participants were sexually active in the past three months. Most of the subjects reported at least one HIV risk behavior such as engaging in sexual intercourse with a male partner without a condom (50%). Factors associated with acceptance of MPTs included perceived safety, long-lasting action, and effectiveness of the formulation. Formulation types preferred by respondents include daily pills (21%), vaginal gels (12%), and inserts (8%). Personal characteristics supporting MPT use include age (30–39) and (40–49) years, married, formally educated, being a housewife, and having not had sexual intercourse with an HIV-positive male partner and having had an unintended pregnancy. Conclusion: Most of the respondents were interested in MPTs as a daily pill. Safety, long-lasting activity, and effectiveness are the top three criteria predicting acceptance. A variety of MPTs are required to be developed to suit the varying needs of different populations. The MPT preferences must be considered during product development to promote future acceptance among women in Nigeria.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

Pelvic Floor Therapy and Initial Interventions for Pelvic Floor Dysfunction in Gynecologic Malignancies.

This review provides evidence-based updates for the first-line management approaches for pelvic floor disorders in patients with gynecologic malignancies, as well as important provider considerations when referring for pelvic floor physical therapy. Currently, there is strong evidence to recommend pelvic floor muscle training as initial treatment for urinary incontinence and for pelvic organ prolapse; some evidence to recommend a more targeted pelvic floor muscle training program for fecal incontinence; and mostly expertise-based evidence to recommend vaginal gels or estrogen to aid with dyspareunia causing sexual dysfunction. More research is greatly needed to understand the role of overactive pelvic floor muscles in survivors with chronic pelvic pain and the treatment of post-radiation pelvic complications such as vaginal stenosis and cystitis. While pelvic floor disorders are common concerns in gynecologic cancer survivors, there are evidence-based initial noninvasive treatment approaches that can provide relief for many individuals.

Design and characterization of nano sponges loaded vaginal gels of Voriconazole

Objectives: The current inquiry of this research job is to build and analyze a bio adhesive vaginal gel that is packed with Voriconazole Nano sponge for an extended residence duration at the point of infection, resulting in a positive drug release profile. Methods: Nano sponges were created using a solvent evaporation process in varied Voriconazole to β-cyclodextrin ratios. Zeta possibility, polydispersity, size of particles analysis, capture efficiency, and surface morphology of Nao sponges are all determined using scanning microscopes with electrons (SEM). FTIR and DSC investigations were used to determine drug excipient compatibility. Carbopol/Hypromellose/Sodium Carboxymethyl cellulose/HPC has been used to make the bio adhesive gel, while both propyl paraben and a methyl para were employed as antioxidants. Triethanolamine, also was used to regulate the pH, resulting in a transparent gel. The gel base has been incorporated with the improved Voriconazole Nano sponge mixture. The pH, viscosity, spread ability, extrudability, and medication content of Nano sponge in mixes of gels were all investigated. The gel's in vivo diffusion has been examined on goat vaginal mucosal. Cellophane membranes was used in an artificial drug release examination. Results: The improved generation of IDLNS12 Nano sponge (drug-polymer ratio 1:1) demonstrated 91.56% entrapment efficiency. The average particle diameter of all formulations was less than 310 nm. The SEM photographs revealed smooth and spherical particles. INSG4 (Carpool and HPC) gel formulation had a viscosity value of 4529 cps at 2-10 RPM, a gel strength of 92.65N load, and an expansion speed of 37.24 g.cm/seconds. At 12.0 minutes, INSG4 achieved 99.98% drug release. And a mucous adhesive time of in excess of 12 hours. Conclusion: These results suggest that Voriconazole-loaded β-cyclodextrin Nano sponge in mucous adhesive gel might be used for managing infections of vagina perpetually.