Discussion
vaginal microflora alterations, vaginal infections, vaginal infection, ProVate, infections, vulvar lotions, vaginal complaints
ADVERSE EVENTS, VAGINAL INFECTION, INFECTIONS, GENITAL INFECTIONS, SECONDARY, BACTERIAL VAGINOSIS
This study was intended to confirm that ProVate does not cause meaningful changes in vaginal microflora compared to the control and that microfloral fluctuations were comparable and can be attributed to regular vaginal microflora alterations unrelated to the use of vaginal devices. The primary and the secondary endpoints were successfully met, indicating that ProVate does not alter the vaginal microflora in a clinically significant manner compared with a ring pessary (control). These results are consistent with those of previous studies [Common practices with existing ring pessaries include their 3–12-month use, removal, cleaning, and reinsertion. Previous data support that vaginal devices do not promote vaginal infections and that vaginal microflora is unstable, with marked variability in the identity and abundance of various microorganisms, irrespective of the presence of a device. Increased vaginal infections were found while using vaginal devices, affecting 6%–33% of users [The Nugent semiquantitative scale, originally developed for premenopausal women, is a simple and accessible method for diagnosing bacterial vaginosis, allowing for easy comparison of pre- and post-results and assessment of the balance between beneficial and non-beneficial microorganisms; hence, it is applicable for any age. Although advanced methods for detecting minimal amounts of nonhuman DNA exist, simple, well-established, semiquantitative Gram stain and plate count methods were utilized to avoid test oversensitivity, which may impact the study outcome.This study is the first to compare possible vaginal microflora changes when using a clean disposable device at every insertion (ProVate) and when a reusable device is used for the first of many usages (control), and sheds light on the following two factors not sufficiently addressed in the regular pessary use practice:(a) the reusability of existing pessaries, and the subsequent level of cleanliness upon reinsertion is less than optimal; hence, insertion of a reusable device with possible remaining biofilms [In this study, the influence of device cleanliness (using only a fresh device: either disposable ProVate, or a new unused package of a control device) and use length (up to 7 and 36 days for ProVate and control devices, respectively) in promoting vaginal microflora changes and in the diagnosis of vaginal infection was examined. Although the results obtained using the two devices are comparable, it should be stressed that the control device was a new clean pessary (not used reusable pessary). This may have positively shifted the results, demonstrating fewer infections or vaginal complaints with the control device than would usually be found while using the same reusable pessary over many repeated insertions for long periods, which might be reason for low rate of vaginal infections and complaints in the control group.The other benefits of using ProVate include the ability to perform home self-insertion using an applicator, no clinic dependency, and shift of control over the medical problem into the hands of women. Additionally, ProVate is disposable and has small dimensions during insertion and removal, short use period, and low expected rate of vaginal infections and complaints, which may contribute considerably to treatment compliance and better acceptance.The study strengths were its randomized, controlled, multicenter design, strict supervision (including a daily diary of adverse events and device follow-up), combined objective laboratory results with subjective complaints as endpoints, and use of a central laboratory for all sites. The benefit of ProVate, without any vaginal infections or complaints when participants replaced 6–9 devices during the study period, has been well demonstrated.One limitation of this trial is the use of control devices only during its primary round (using a new clean package), which prevented data collection regarding vaginal infections and complaints over long-term use, when biofilms accumulate and insufficient cleaning is expected. Another limitation was that only a few microorganisms (although they are responsible for the vast majority of genital infections) were examined and that study restrictions (e.g., avoidance of vulvar lotions, antibiotics, steroids, and intercourse before sampling), which differ greatly from typical behaviors, were applied.In conclusion, the study results confirm that, compared with the control device, ProVate does not cause meaningful changes in the vaginal microflora and that microfloral fluctuations can be attributed to regular vaginal microflora alterations unrelated to vaginal device use. Together with its other features, ProVate may increase the acceptance and compliance rates among women with POP receiving nonsurgical management. Further studies without restrictions are needed to validate the results of the use ProVate and reusable ring pessaries, regardless of cleanliness and length of use.