The principle of participant distribution into groups is the type of surgical
intervention and preoperative preparation. Total up to 135 participants with pelvic
organs prolapse I-II degree of severity, or any other pathology of pelvic organs, which
require surgical intervention will be involved in the study. Participants will be divided
into three groups: group with anterior and/or posterior (A/P) colporrhaphy and laser
preoperative treatment (laser treatment group), group with A/P colporrhaphy only (control
group 1), and group with any other surgical intervention of pelvic area with obtaining a
biopsy of the vaginal wall (control group 2), by 45 participants in each group.
The types of examination of each group are the same and include:
General methods: physical examination, clinical blood analysis including glucose
determination, clinical urine test, vaginal smear for flora and oncocytology, pelvic
ultrasound, tests for hepatitis B, C viruses, human immunodeficiency viruses and
syphilis, blood clotting tests, blood type and rhesus factor determination,
electrocardiography, colposcopy, consultation of a therapist about the absence of
contraindications for surgical treatment.
Special methods: filling out the questionnaire (Pelvic Floor Distress Inventory
Questionnaire, The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire,
International Consultation on Incontinence Questionnaire - Short Form, Pelvic Floor
Impact Questionnaire), Vaginal Health Index determination, Doppler ultrasonography of
vagina, histological examination, immunohistochemical examination, optical coherence
tomography (OCT) (elastography).
The treatment procedure of this study is the laser treatment of the vagina and vulva with
a "Magic Max" laser ("Magic Gyno" from August 2024) with subsequent monitoring.
Genetic testing: genetic testing for the following markers will be carried out:
ESR1 rs2234693 (estrogen receptor 1), ESR1 rs2228480 (estrogen receptor 1), COL3A1
rs1800255 (collagen type III alpha 1 chain), COL14A1 rs4870723 (collagen type XIV alpha 1
chain), MMP9 rs3918253 (matrix metallopeptidase 9), MMP10 rs17435959 (matrix
metallopeptidase 10), LOXL1 rs2304719 (lysyl oxidase like 1), WNT4 rs3820282 (Wnt family
member 4), MMP2 rs243865 (matrix metalloproteinase type 2), TIMP2 rs2277698 (tissue
inhibitor of metalloproteinase-2), CD31 / PECAM1 rs1131012 (platelet-endothelial cell
adhesion molecule 1), Ki67 rs11016076 (proliferation marker Ki67).
Treatment Technique:
Laser treatment procedure will be carried out in three stages. In total, three procedures
will be performed with an interval of 4 weeks. Colporrhaphy will be carried out 1 month
after last treatment. Three follow-up visits will follow: 1, 6 and 12 months after
colporrhaphy.
During the procedure, the following sequence of actions will be performed:
st Stage - vaginal processing with a conical mirror handpiece,
nd Stage - vaginal processing with a corner mirror handpiece,
rd Stage - external vulva and paraurethral region processing with a switched beam
diameter handpiece.
Laser radiation is emitted by a series of pulses following each other through a pause.
The duration of one pulse is 20-200 nanoseconds (ns), the pause between pulses is 30
microseconds (us). The energy of one pulse is about 1.5 millijoule (mJ). The procedure is
performed without anesthesia. The doctor always focuses on the participant's feeling of
warmth.
Participants of all groups will be tested with the general methods necessary to include
the participant in the study at the first visit.
Control Technique:
In the control groups general surgery preparation protocol (sanitation of vagina) will be
used as a therapeutic tool. After completing of preparation course, the operation will be
performed.
Operation technique:
A part of the stretched vaginal wall in the posterior fornix area including the mucous
membrane and muscle layer will be excised with its further suturing during colporrhaphy
surgery (the excised material will be examined). This will allow comparing the vaginal
walls state at the time of surgery after laser treatment and without it, and with the age
norm.
Participants of all groups will be tested with the general methods necessary to include
the patient in the study at the first visit.
For the laser treatment group: Studies will be carried out using filling out the
questionnaires, Vaginal Health Index determination, and Doppler ultrasonography, and then
laser treatment of the vagina, vulva and paraurethral region will be performed during the
2nd, 3d, and 4th visits. Filling out the questionnaires, Vaginal Health Index
determination, and Doppler ultrasonography will be repeated during the 5th visit (1 month
after last laser treatment and 1 day before colporrhaphy). Vaginal biopsy for
histological examination, immunohistochemical examination, and optical coherence
tomography (elastography) will be carried out during A/P colporrhaphy in the 6th visit.
Physical examination only will be carried out during the 7th (follow-up) visit - 1 month
after colporrhaphy. Filling out the questionnaires, Vaginal Health Index determination,
and Doppler ultrasonography will be carried out during 8th and 9th (follow-up) visits - 6
and 12 months after colporrhaphy.
For control group 1: Studies will be carried out using filling out the questionnaires,
Vaginal Health Index determination, and Doppler ultrasonography during the 1st visit
after including patient. Vaginal biopsy for histological examination, immunohistochemical
examination, and optical coherence tomography (elastography) will be carried out during
A/P colporrhaphy in the 2nd visit. Physical examination only will be carried out during
the 3th (follow-up) visit - 1 month after colporrhaphy. Filling out the questionnaire,
Vaginal Health Index determination, and Doppler ultrasonography will be carried out
during 4th and 5th (follow-up) visits - 6 and 12 months after colporrhaphy. Buccal smear
collection will be carried out during 4th follow up visit (6 months after colporrhaphy).
Thus, a direct comparison between laser preoperational treatment and lack of
preoperational treatment will be made during the investigation, 6 and 12 months after the
end of each type of treatment.
For control group 2: Studies will be carried out using filling out the questionnaires,
Vaginal Health Index determination, and Doppler ultrasonography during the 1st visit
after including participant. Vaginal biopsy for histological examination,
immunohistochemical examination, and optical coherence tomography (elastography) will be
carried out during A/P colporrhaphy in the 2nd visit (no more than 1 month after 1st
visit). The obtained data will allow to study the tissues of the vaginal wall in normal
conditions.
The study will be carried out with the participation of several clinics:
(recruting, filling out IRC - Individual Registration Cards, buccal smear collection)
(colporrhaphy and biopsy)
Privolzhsky Research Medical University (main scientific coordinator, histological
examination, immunohistochemical examination, and optical coherence tomography
(elastography)), genetic examination,
LLC "Medical Center" AIST "" (location of laser equipment, recruiting, filling out
IRC - Individual Registration Cards laser treatment, special tests, buccal smear
collection),
State Budgetary Institution of Health Care of the Nizhny Novgorod Region "Nizhny
Novgorod Regional Clinical Oncological Dispensary" (colporrhaphy and biopsy, buccal
smear collection),
Clinic "Preventamed", LLC "Aesthetic Medicine" (recruting, filling out IRC -
Individual Registration Cards, buccal smear collection),
State-Funded Healthcare Institution of the Nizhny Novgorod region "Nizhny Novgorod
Regional Clinical Hospital named after N.A. Semashko" (recruting, filling out IRC -
Individual Registration Cards, buccal smear collection),
Birth house №4 of the Leninskiy District of Nizhny Novgorod named after A.F.
Dobrotina (colporrhaphy and biopsy) All data obtained during the study will be
transferred to the manufacturer of laser equipment "MeLSyTech" Ltd.
The study will be monitored by "MeLSyTech" Ltd as follows:
Once a month, monitoring of provided documents (copies of individual registration
records of participants, informed consent, test results) for the complete filling of
the forms; the clarity of filling out forms, the possibility of systematizing
information from the forms of their assessment;
Once every six months, monitoring will be conducted with a coordinator visit of the
research center and analysis activities, such as participants recruitment, data
collection, data management, data analysis, reporting for adverse events, and change
management;
Once a year, the investigator submits a clinical evaluation report to the sponsor.
Statistics
The analysis will be carried out both between groups of participants receiving different
types of therapy (analysis of independent groups) and within groups at different time
intervals (analysis of matched groups).
Before performing statistical analysis of the data, the distribution type of the
variables will be assessed. To assess the normality of distribution for each variable,
histograms of frequency distributions will be visually evaluated, indicators of skewness,
kurtosis, and the D'Agostino-Pearson normality test will be used.
In addition to checking the type of distribution of variables, the equality of variances
of the studied groups will be assessed using the methods of analysis of variance, in
particular the Brown-Forsythe test.
Methods of descriptive analysis will be used depending on the type of distribution of the
variable. With a normal distribution, the mean (M) and standard deviation (SD) will be
calculated. In case of an nongaussian distribution, the median (Me) and interquartile
range will be calculated. Different algorithms of statistical analysis will be applied
depending on the type of distribution of variables.
Comparison of the paired and unpaired groups with a normal distribution, in case of the
equality of the variances, will be carried out by the methods of analysis of variance
ANOVA. Comparison of groups in pairs will be performed using the post-hoc method of
posterior multiple comparisons (Tukey test).
Comparison of groups in which variables do not follow the normal distribution will be
carried out using the methods of nonparametric analysis of variations: the Kruskal-Wallis
test (ANOVA tests) for independent groups and the Friedman test for matched groups.
Dunn's multiple comparison test will be used to assess intergroup differences.
Before assessing intergroup differences, the initial samples (1 visit) will be analyzed
for identity using ANOVA or nonparametric Kruskal-Wallis tests (depending on the type of
data). In case of significant differences in the samples, the search and removal of
extremely deviating values (outliers) will be carried out.
Differences will be considered statistically significant if the significance P values are
<0.05.