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).