Methods
This study was a prospective, single-blind, randomized, controlled, pilot trial using a within-subject cross-over design. The study was approved by the institutional review board of the Galilee Medical Center of the Israeli Health Ministry, on July 23, 2017; authorization number: 0043-17-NHR. ClinicalTrials.gov Identifier: NCT03197337. Written informed consent was obtained from all subjects.
Participants were women 18 to 35 years of age who met Friedrich’s first two criteria10 for vulvar vestibular syndrome (referred to here as PV): severe pain in the vulvar vestibule on touch or attempted vaginal entry and tenderness to pressure (i.e., with a Q-tip applicator) localized within the vulvar vestibule. We included only women who were diagnosed with either moderate or severe PV (able to have sexual intercourse but with immense pain or unable to have sexual intercourse at all).11 Patients were excluded if they had vulvar pain caused by a specific disorder (such as that defined by the 2015 of the consensus terminology),1 had been diagnosed with generalized vulvodynia, had been previously treated surgically for vulvodynia, had an acute genital infection or inflammation during the trial period or recovered from such an episode within 14 days, had pelvic pain or sensitivity on bimanual examination, were diagnosed with pelvic organ prolapse of any degree, had any significant medical condition, or had a history of abnormal cervix cytology.
Twenty participants were recruited (Figure 1). Each patient was examined by the same vulvar disease specialist who ruled out other causes of dyspareunia and verified the diagnosis of PV by using the Q-tip test and Friedrich’s criteria10 (extreme pain elicited by applying light pressure with a cotton wide swab on seven fixed points at the introitus).
During this test, patients were asked to rank their pain intensity on a scale from 0 to 10 (0, experiencing no pain; 10, experiencing maximum pain) to document their baseline pain level.12
Subsequently, all patients underwent trial manipulation, which involved applying pressure with a device sufficiently wide to stretch the posterior fornix without overstretching it, thereby temporarily providing support to the USL. To identify the posterior fornix, a lubricated narrow speculum was used, and a swab sufficiently wide to support the USLs was inserted through it (Figure S2). After placing the wide swab stick in the posterior fornix, the speculum was immediately removed, leaving the wide swab in its place (Figure S3). Then, we crossed over to perform sham manipulation (insertion of the device to the posterior fornix without applying pressure).
During each manipulation, and while the wide swab stick and supporting device were in the posterior fornix, the Q-tip test was re-performed (Figure 2) and patients were again asked to rank their vestibular foci pain intensity.
To determine if the results were affected by the manipulation order, subjects were computer-randomized into two groups before manipulation. Subjects in the first group (trial first group) underwent trial manipulation first, followed by sham manipulation; however, the second group (sham first group) underwent sham manipulation first, followed by trial manipulation.
After collecting all data, the average pain intensity levels during the different scenarios were calculated for each group. We used a Wilcoxon rank-sum test to determine whether the manipulation order affected the differences in pain intensity compared with the baseline pain level. The average pain levels under the different conditions using a paired sample t-test were determined for the following pairs: baseline pain level and trial manipulation pain level (baseline-trial); baseline pain level and sham manipulation pain level (baseline-sham); and trial manipulation pain level and sham manipulation pain level (trial-sham).