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Contraception Feb 2022The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for acceptability of the vaginal ring across indications to support dapivirine and multipurpose prevention technology ring introduction and roll out.
STUDY DESIGN
This systematic review and meta-analysis followed PRISMA guidelines. We searched PubMed, Web of Science, Embase, and grey literature for publications reporting favorable ring acceptability and secondary outcomes involving actual ring use (comfort, ease of ring use, ring comfort during sex, expulsions, and vaginal symptoms) or hypothetical acceptability for any indication published January 1, 1970-June 15, 2021. We estimated random-effects pooled prevalence, assessing between-study variation using meta-regression.
RESULTS
Of 2,234 records, we included 123 studies with 40,434 actual and hypothetical ring users. The primary outcome assessment included 50 studies with 60 ring subgroups totaling 19,271 ring users. The favorable acceptability pooled prevalence was 85.6% (95%CI 81.3, 89.0), while hypothetical acceptability among non-ring users was 27.6% (95%CI 17.5, 40.5). In meta-regression, acceptability was higher in menopause (95.4%; 95%CI 88.4, 98.2) compared to contraceptive rings (83.7%; 95%CI 75.6, 89.5). Acceptability was lower in pharmacokinetic studies (50%; 95%CI 22.1, 77.9) compared to RCTs (89.5%; 95%CI 85.8.92.4) and in studies assessing acceptability at ≥12 months (78.5%; 95%CI 66.5, 87.1) versus studies assessing acceptability at <3 months (91.9%; 95%CI 83.7, 96.1). European (90.6%; 95%CI 83.9, 94.7), Asian (97.1%; 95%CI 92.0, 99.0), and multi-region studies (93.5%; 95%CI 84.6, 97.4) reported more favorable acceptability compared to African studies (59.4%; 95%CI 38.3, 77.5). Secondary outcomes were similarly favorable, including ring comfort (92.9%; 95%CI 89.2, 95.4), ease of use (90.9%; 95%CI 86.5, 94.0), and comfort during sex (82.7%; 95%CI 76.4, 87.6). Limitations include inconsistent outcome definitions and unmeasured factors affecting acceptability.
CONCLUSIONS
Women who used vaginal rings reported they were acceptable across indications geographic regions and indications. Policy makers should consider the ring as an important option for pregnancy and HIV prevention drug development.
IMPLICATIONS
This review found favorable acceptability among vaginal ring users across indications and geographic areas, in contrast to low hypothetical acceptability among non-users. Vaginal rings are an important drug delivery system for pregnancy and HIV preventions, and scale-up should plan to address initial hesitancy among new users.
Topics: Contraceptive Devices, Female; Female; Humans; Pregnancy; Vagina
PubMed: 34644609
DOI: 10.1016/j.contraception.2021.10.001 -
Clinical Hematology International Sep 2019Female recipients of hematopoietic cell transplant (HCT) may develop lower genital tract (LGT) dysplasia or new malignancies. A comprehensive systematic review to... (Review)
Review
Female recipients of hematopoietic cell transplant (HCT) may develop lower genital tract (LGT) dysplasia or new malignancies. A comprehensive systematic review to delineate the occurrence and risk factors for post-HCT LGT precancer and cancer in women was conducted via electronic search of the Cochrane Library, PubMed, Embase, Wiley Online Library, from 1990 to 2018. All studies on the risk, presentation, or incidence of LGT (cervix, vulva, vagina) precancer or cancer post-HCT were included. Reviews, case reports, meta-analysis, book chapters, and studies without the relevant clinical outcomes were excluded. Post-HCT incidence and risk factors for developing LGT precancer or cancer were assessed and determined. Twenty-two out of the original 344 studies met the selection criteria. The risk of LGT cancers in allo-HCT recipients was found to be significantly higher than in the general population, with the standardized incidence ratios of 1.5-48 for cervical cancer and from 19 to 287 for dysplasia. Our review portrays an increased risk of premalignant and malignant neoplasms of female LGT, which have an incompletely described epidemiology and outcomes. Similar to other immunocompromised states, HCT recipients require specific cervical screening guidelines and can greatly benefit from HPV vaccinations. However, there is a lack of prospective data regarding optimum cervical screening in HCT recipients and limited programs offer HPV vaccinations worldwide.
PubMed: 34595424
DOI: 10.2991/chi.d.190519.001 -
Journal of Epidemiology and Global... Jun 2024Latina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial-ethnic...
BACKGROUND
Latina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial-ethnic groups. This systematic review explores the relationship between the cervicovaginal microbiome and human papillomavirus infection, cervical dysplasia, and cervical cancer in Latinas.
METHODS
The review abides by the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, EMBASE, and Scopus databases were searched from January 2000 through November 11, 2022. The review included observational studies reporting on the cervicovaginal microbiota in premenopausal Latina women with human papillomavirus infection, cervical dysplasia, and cervical cancer.
RESULTS
Twenty-five articles were eligible for final inclusion (N = 131,183). Forty-two unique bacteria were reported in the cervicovaginal microbiome of Latinas. Seven bacteria: Lactobacillus crispatus, Lactobacillus iners, Chlamydia trachomatis, Prevotella spp., Prevotella amnii, Fusobacterium spp. and Sneathia spp. were enriched across multiple stages of cervical carcinogenesis in Latinas. Therefore, the total number of reported bacteria includes four bacteria associated with the healthy state, 16 bacteria enriched in human papillomavirus outcomes, 24 unique bacteria associated with abnormal cytology/dysplasia, and five bacteria associated with cervical cancer. Furthermore, three studies reported significantly higher alpha and beta diversity in Latinas with cervical dysplasia and cancer compared to controls. Lactobacillus depletion and an increased abundance of L. iners in Latinas compared to non-Latinas, regardless of human papillomavirus status or lesions, were observed.
CONCLUSIONS
The identification of 42 unique bacteria and their enrichment in cervical carcinogenesis can guide future cervicovaginal microbiome research to better inform cervical cancer prevention strategies in Latinas.
Topics: Humans; Female; Papillomavirus Infections; Uterine Cervical Neoplasms; Hispanic or Latino; Vagina; Microbiota; Uterine Cervical Dysplasia; Carcinogenesis
PubMed: 38407720
DOI: 10.1007/s44197-024-00201-z -
Neurourology and Urodynamics Jan 2022To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of... (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes.
METHODS
A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated.
RESULTS
Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-β1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant.
CONCLUSIONS
Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.
Topics: Animals; Estrogens; Female; Humans; Vagina; Wound Healing
PubMed: 34643282
DOI: 10.1002/nau.24819 -
Journal of Personalized Medicine Feb 2022(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected... (Review)
Review
(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected in <1%. The objective of the study was to provide a systematic review of the literature of GPA patients with gynecological involvement. (2) Methods: PubMed and Embase were searched from inception to July 2021 for GPA patients with gynecological involvement Medical Subject Headings (MeSH) and free-text terms. Exclusion criteria were other language, review articles, pregnancy, fertility, or male patients. Data were extracted on clinical evolution, symptoms, examinations findings, diagnosis delay, treatment, outcome, patient status, and follow-up. (3) Results: Seventeen studies included data from patients with GPA and primary or relapsed gynecological involvement. 68% of the authors of this review thought the patient had cancer. The main gynecological symptom is bleeding, but exclusive gynecologic symptomatology is rare (ENT: 63%, lungs: 44%, kidneys-urinary tract: 53%). GPA could affect all areas of the genital tract, but the most frequent location is the uterine cervix. Medical treatment for GPA is effective. (4) Conclusions: GPA of the female genital tract must be considered when biopsies of an ulcerated malignant-appearing cervical or vaginal mass are negative for malignancy even when they are unspecific. Rheumatology consultation is indicated.
PubMed: 35207776
DOI: 10.3390/jpm12020289 -
Revista Da Associacao Medica Brasileira... Feb 2022
Meta-Analysis
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Vulvovaginal; Female; Humans; Recurrence; Vagina
PubMed: 35239893
DOI: 10.1590/1806-9282.20210916 -
Scientific Reports Aug 2023Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18%... (Meta-Analysis)
Meta-Analysis
Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.
Topics: Infant, Newborn; Pregnancy; Child; Humans; Female; Vaginosis, Bacterial; Birth Weight; Premature Birth; Vagina; Blood Coagulation Tests
PubMed: 37626108
DOI: 10.1038/s41598-023-40993-x -
Experimental and Therapeutic Medicine Oct 2020Vaginitis, also known as vulvovaginitis, is an inflammation of the vagina and vulva and a common disease in females. It is thought to be caused by vaginal dysbiosis and...
Vaginitis, also known as vulvovaginitis, is an inflammation of the vagina and vulva and a common disease in females. It is thought to be caused by vaginal dysbiosis and improved by probiotics. Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) are the major types of vaginal infections. The present systematic review and meta-analysis aimed to clarify the efficacy of probiotics in the treatment of common vaginal infections in non-pregnant females. Literature on randomized controlled trials and two-armed prospective studies on any intervention with probiotics published until December 24th, 2018 was searched in the PubMed, Cochrane and EMBASE databases. The outcomes of interest were recurrence rate, cure rate, remission rate and normal vaginal flora restoration. Finally, a total of 30 studies on bacterial vaginosis (BV) and/or VVC were included and stratified into 3 study types based on treatment design as follows: Type I, antibiotic/probiotics vs. antibiotics/antifungals (22 studies); Type II, probiotics vs. placebo (5 studies); Type III, probiotics vs. antibiotics (3 studies). The type I studies comprised 1,788 non-pregnant females and had the highest inter-study comparability in post-treatment follow-up design and meta-analysis outcome data. Probiotics interventions were significantly associated with a lower recurrence rate of vaginitis [pooled odds ratio (OR)=0.27, 95% CI: 0.18-0.41, P<0.001] and higher cure/remission rate (pooled OR=2.28, 95% CI: 1.20-4.32, P=0.011). However, a significant increase in normal vaginal flora after probiotic treatment was observed only in BV (pooled OR=4.55, 95% CI: 1.44-14.35, P=0.01). In addition, supportive but heterogeneous results were obtained from the 6-month follow-up data of Type-I studies, different infection types and supplementary analysis of Type-II studies. In conclusion, probiotics have a significant short-term effect in the treatment of common vaginal infections in non-pregnant females. In order to evaluate the long-term effects of probiotics in common vaginal infections, it is worthwhile to perform higher-quality clinical trials in the future.
PubMed: 32855726
DOI: 10.3892/etm.2020.9090 -
Human Reproduction Open 2021Is there an ideal imaging modality for the detection of uterosacral ligaments/torus uterinus (USL), rectovaginal septum (RVS) and vaginal deep endometriosis (DE) in...
Meta-analysis and systematic review to determine the optimal imaging modality for the detection of uterosacral ligaments/torus uterinus, rectovaginal septum and vaginal deep endometriosis.
STUDY QUESTION
Is there an ideal imaging modality for the detection of uterosacral ligaments/torus uterinus (USL), rectovaginal septum (RVS) and vaginal deep endometriosis (DE) in women with a clinical history of endometriosis?
SUMMARY ANSWER
The sensitivity for the detection of USL, RVS and vaginal DE using MRI seems to be better than transvaginal ultrasonography (TVS), whilst the specificity of both were excellent.
WHAT IS KNOWN ALREADY
The surgical management of women with DE can be complex and requires advanced laparoscopic skills with maximal cytoreduction being vital at the first procedure to provide the greatest symptomatic benefit. Owing to a correlation of TVS findings with surgical findings, preoperative imaging has been used to adequately consent women and plan the appropriate surgery. However, until publication of the consensus statement by the International Deep Endometriosis Analysis Group in 2016, there were significant variations within the terms and definitions used to describe DE in the pelvis.
STUDY DESIGN SIZE DURATION
A systematic review and meta-analysis was conducted using Embase, Google Scholar, Medline, PubMed and Scopus to identify studies published from inception to May 2020, of which only those from 2010 were included owing to the increased proficiency of the sonographers and advancements in technology.
PARTICIPANTS/MATERIALS SETTING METHODS
All prospective studies that preoperatively assessed any imaging modality for the detection of DE in the USL, RVS and vagina and correlated with the reference standard of surgical data were considered eligible. Study eligibility was restricted to those including a minimum of 10 unaffected and 10 affected participants.
MAIN RESULTS AND THE ROLE OF CHANCE
There were 1977 references identified from which 10 studies (n = 1188) were included in the final analysis. For the detection of USL DE, the overall pooled sensitivity and specificity for all TVS techniques were 60% (95% CI 32-82%) and 95% (95% CI 90-98%), respectively, and for all MRI techniques were 81% (95% CI 66-90%) and 83% (95% CI 62-94%), respectively. For the detection of RVS DE, the overall pooled sensitivity and specificity for all TVS techniques were 57% (95% CI 30-80%) and 100% (95% CI 92-100%), respectively. For the detection of vaginal DE, the overall pooled sensitivity and specificity for all TVS techniques were 52% (95% CI 29-74%) and 98% (95% CI 95-99%), respectively, and for all MRI techniques were 64% (95% CI 40-83%) and 98% (96% CI 93-99%). Pooled analyses were not possible for other imaging modalities.
LIMITATIONS REASONS FOR CAUTION
There was a low quality of evidence given the high risk of bias and heterogeneity in the included studies. There are also potential biases secondary to the risk of misdiagnosis at surgery owing to a lack of either histopathological findings or expertise, coupled with the surgeons not being blinded. Furthermore, the varying surgical experience and the lack of clarity regarding complete surgical clearance, thereby also contributing to the lack of histopathology, could also explain the wide range of pre-test probability of disease.
WIDER IMPLICATIONS OF THE FINDINGS
MRI outperformed TVS for the per-operative diagnosis of USL, RVS and vaginal DE with higher sensitivities, although the specificities for both were excellent. There were improved results with other imaging modalities, such as rectal endoscopy-sonography, as well as the addition of bowel preparation or ultrasound gel to either TVS or MRI, although these are based on individual studies.
STUDY FUNDING/COMPETING INTERESTS
No funding was received for this study. M.L. reports personal fees from GE Healthcare, grants from the Australian Women's and Children's Foundation, outside the submitted work. B.W.M. reports grants from NHMRC, outside the submitted work. G.C. reports personal fees from GE Healthcare, outside the submitted work; and is on the Endometriosis Advisory Board for Roche Diagnostics.
REGISTRATION NUMBER
Prospective registration with PROSPERO (CRD42017059872) was obtained.
PubMed: 34869918
DOI: 10.1093/hropen/hoab041 -
International Journal of Radiation... May 2024Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue... (Review)
Review
PURPOSE
Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue complication probability (NTCP) models quantify toxicity risk and aid in optimizing radiation therapy to minimize side effects. However, it is unclear which predictors to include in an NTCP model. The aim of this systematic review was to provide an overview of the identified predictors contributing to gastrointestinal (GI), genitourinary (GU), and vaginal toxicities and insufficiency fractures for LACC.
METHODS AND MATERIALS
A systematic search was performed and articles evaluating the relationship between predictors and toxicities in women with LACC treated with primary chemoradiation were included. The Quality In Prognosis Studies tool was used to assess risk of bias, with high-risk studies being excluded from further analysis. Relationships between dose-volume parameters, patient and treatment characteristics, and toxicity endpoints were analyzed.
RESULTS
Seventy-three studies were identified. Twenty-six had a low or moderate risk of bias and were therefore included. Brachytherapy-related dose-volume parameters of the GI tract, including rectum and bowel equivalent dose in 2 Gy fractions (EQD2) D2 cm, were frequently related to toxicities, unlike GU dose-volume parameters. Furthermore, (recto)vaginal point doses predicted toxicities. Few studies evaluated external beam radiation therapy dose-volume parameters and identified rectum EQD2 V30 Gy, V40 Gy, and V55 Gy, bowel and bladder EQD2 V40 Gy as toxicity predictors. Also, total reference air kerma and vaginal reference length were associated with toxicities. Relationships between patient characteristics and GI toxicity were inconsistent. The extent of vaginal involvement at diagnosis, baseline symptoms, and obesity predicted GU or vaginal toxicities. Only 1 study evaluated insufficiency fractures and demonstrated lower pretreatment bone densities to be associated.
CONCLUSIONS
This review detected multiple candidate predictors of toxicity. Larger studies should consider insufficiency fractures, assess dose levels from external beam radiation therapy, and quantify the relationship between the predictors and treatment-related toxicities in women with LACC to further facilitate NTCP model development for clinical use.
Topics: Humans; Female; Uterine Cervical Neoplasms; Fractures, Stress; Urinary Bladder; Chemoradiotherapy; Brachytherapy; Rectum; Vagina; Radiotherapy Dosage
PubMed: 37979708
DOI: 10.1016/j.ijrobp.2023.11.010