Histological Modifications of Postmenopausal Vaginal Mucosa After Repeated Carbon Dioxide (CO2) Laser Treatment

Study Overview
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Brief Summary
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To assess the long-term histological and clinical efficacy of MonaLisa Touch procedure for the management of the Genitourinary Syndrome of Menopause (GSM) in postmenopausal female patients.

Detailed Description
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The investigator propose a prospective case series of 15 postmenopausal women with bothersome symptoms of GSM treated with MonaLisa Touch CO2 laser. The investigator hypothesize that even in the long term MonaLisa Touch will significantly improve GSM histologically and clinically from baseline. The primary outcome objective of the study is to evaluate the histological modifications of the vaginal mucosa after repeated CO2 Monalisa Touch laser treatment. The investigator shall evaluate the role of this treatment by calculating the difference in vaginal epithelial thickness between the biopsy obtained before the start of laser treatment and the biopsy obtained after treatment. In addition, the study will analyze the safety of repeated laser treatments verifying the absence of fibrosis formation in the vaginal mucosa. Secondary objectives of the study will include an evaluation of the clinical effects associated with repeated Monalisa Touch CO2 laser treatments using validated questionnaires. All participants will be screened to ensure inclusion/exclusion criteria are met. A biopsy will be taken from each patient one month before the first laser treatment and one month after the last laser treatment. The MonaLisa treatment will be performed monthly for 3 months. MonaLisa treatment with fractional microablative laser system. For subjects with concomitant vulvar symptoms, vulvar treatment will be done. Biopsy samples will be analyzed with Hematoxylin- Eosin and Trichrome staining, Periodic acid-Schiff (PAS) reaction for glycogen and immunohistochemistry for CD34, a vessel marker. All clinical questionnaires will be assessed at baseline and at one month after the last session.

Official Title
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Histological Modifications of Postmenopausal Vaginal Mucosa After Repeated CO2 Laser

Conditions
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Vaginal Atrophy, Breast Cancer Female, Dyspareunia

Intervention / Treatment
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* Device: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Italian speaking and able to give informed consent. Menopausal females with absence of menstruation for at least 12 months. Presence of GSM symptoms. Completion of at least two cycles of three laser treatments sessions in previous years. Prolapse stage < II, according to the pelvic organ prolapse quantification (POP-Q) system. No pelvic surgery within 6 months prior to treatment. Understanding and acceptance to the obligation to return to all scheduled visits and follow-ups. Exclusion Criteria: Inability of give informed consent History of vulvovaginal condyloma, vaginal intraepithelial neoplasia (VAIN), vaginal carcinoma, lichen sclerosis, lichen planus. History of cancers of the lower genital tract (cervix, uterus, vagina). History of pelvic radiotherapy. Personal history of genital fistula, a thin recto-vaginal septum as determined by the investigator or personal history of a fourth degree laceration during screening physical exam. Any other medical condition that the investigators feel would compromise the study. Acute or recurrent urinary tract infection (UTI), or genital infection (e.g. bacterial vaginosis, herpes genitalis, candida). Stage III or IV pelvic organ prolapse. History of any female sexual disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient<br>All participants will be screened to ensure inclusion/exclusion criteria are met. A biopsy will be taken from each patient one month before the first laser treatment and one month after the last laser treatment. The MonaLisa treatment will be performed monthly for 3 months. A clinical evaluation will be recorded for each patient using validated questionnaires at baseline and one month after the last procedure. | Device: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy<br>* SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy; MonaLisa Touch CO2 fractionated laser<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microscopic evaluation for vaginal epithelial thickness | The vaginal epithelial thickness will be measured in micrometers. Then the difference in vaginal epithelial thickness between the biopsy obtained before and after the start of laser treatment will be calculated, considering a 20% increase as significant. | 4-5 weeks after the last treatment | 
| Microscopic evaluation of number of papillae | The number of papillae in bioptic samples will be analyzed with Hematoxylin- Eosin and Trichrome staining. | 4-5 weeks after the last treatment | 
| Microscopic evaluation of glycogen amount | The amount of glycogen present at the epithelial level and the ratio between the number of type I collagen fibers and type III will be evaluated with PAS reaction for glycogen. | 4-5 weeks after the last treatment | 
| Microscopic evaluation of number and size of the vessels | The number and size of the vessels present in the subepithelial layer will be evaluated using immunohistochemistry for CD34, a vessel marker. | 4-5 weeks after the last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validated questionnaires VHI | Vaginal Health Index (VHI) for evaluation of vaginal atrophy severity that is composed by the sum of 6 fields (min score 1 max score 5). The least score (6) is the worst; the maximum score (30) is the best. | 4-5 weeks after the last treatment | 
| Validated questionnaires FSFI | Female Sexual Function Index (FSFI) questionnaire which will assess female sexual function that is composed of 19 fields. The minimum score is 2 in the worst situation; maximum score is 36 in the best situation | 4-5 weeks after the last treatment | 
| Validated questionnaires UDI-6 | Urinary Distress Inventory-6 (UDI-6) is a 6 fields questionnaires on voiding function. The minimum score is 0 in absence of symptoms; 18 is the maximum score in the worst situation. | 4-5 weeks after the last treatment | 
| Validated questionnaires ICIQ-UI | International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) which will evaluate the extent of urinary symptoms. It is divided into two parts: questions 1, 2 and 3 are added together and the maximum score is 22, in worst condition; a score of zero is obtained in asymptomatic patients. The last is a describing question. | 4-5 weeks after the last treatment | 
| Validated questionnaires LIKERT | 5-point Likert scale is made to assess the impact of GSM symptoms on quality of life (QoL). It is a descriptive question. | 4-5 weeks after the last treatment |