Energy-Based Devices for Vaginal Use

ENERGY-BASED DEVICES FOR VAGINAL USE

• None

• “Instead of the a bladder lift, can I have the new laser procedure.”

• ”I want to avoid surgery, my other doctor told me the laser would fix my prolapse.”

• I charge $2400 for all 3 treatments. Anyone with SUI, POP, atrophy, or dyspareunia I offer as a treatment option. We market on Facebook, local TV, and newspaper.”

• Cost $900/session, $1200, 2100, 2400

• “Treat local docs, NP, wives for free”

• Discuss energy based devices for vaginal use. • Explore the evidence for energy- based devices for vaginal use: – sexual function – prolapse – urinary incontinence – genitourinary syndrome of menopause (GSM) • Review current position statements

• Energy-based devices may induce wound healing, stimulate collagen and elastin fiber formation.

• CO2 – creates microscopic incision in the vaginal tissue, stimulating a healing response -> collagen production and thickened skin, lubrication, elasticity

• Erbium:YAG – using hyperthermia, causes deep tissue remodeling, new collagen formation & contraction of its fibers

• Radiofrequency – vibrates molecules, creates heat, and stimulates collagen (elasticity) production as well as blood flow (more moisture)

• Light Amplification by Stimulated Emission of Radiation

• Two laser devices used for vaginal therapy: – Pulsed CO2 (stimulate collagen) – Er:YAG (cause tissue contraction)

– 2-5 (3) treatments, 6 weeks apart -> last 1 year – Nothing per vagina x ?3 days

© UNIVERSITY OF UTAH HEALTH • Radio-frequency devices – Induce collagen contraction, neocollagenesis, vascularization, and growth factor infiltration – MOA: heat shock protein activation and inflammation

• 3 weekly treatments – $1,000 -1,200 per treatment – Jump right back in

• Atrophy • Urinary incontinence • Prolapse • Vulvar disorders (lichen, vestibulitis) • Vaginal laxity • Recurrent vaginal/urinary infections • Sexual dysfunction

• Mona Lisa Touch • Viveve –THERMIVa • Venus Fiore • FemiLift • Exilis Ultra • IntimaLase Femme • IncontiLase • JOULE • Ultra Femme 360 • FomaV/Fractora V

• Definition??

• Age, culture, societal norms, context

• Rx: physical therapy, surgical procedures

• LASERS????

• 2016 – RCT, prospective, sham-controlled, single blinded (RF) – 9 centers: Canada, Italy, Spain, Japan – Subjects with self-reported vaginal laxity, 1 prior VD, normal Gyn exam

– Active (90 J/cm2) vs. Sham (1 J/cm2)

– Outcome at 6 months: “no vaginal laxity” via VLQ • 43.5% vs. 19.6% (p=.002) • AE: 11.1% vs 12.3%

Krychman et al. J Womens Health 2018.

• FSFI

• Evaluates/domains: Desire, Arousal, Lubrication, Orgasm, Satisfaction, and Pain

• Recall period is past 4 weeks.

• For individual domain scores, the scores of the individual items that comprise the domain are summed, and the sum is multiplied by the domain factor.

• The six domain scores are summed to obtain the full scale score.

• A domain score of zero indicates that the subject reported having no sexual activity during the past month.

• The total score is the sum of the domain scores and ranges from 2-36.

• Dysfunction is noted if score is < 27.

Rosen et al. Journal of Sex & Marital Therapy. 2000 Weigel et al. Journal of Sex & Marital Therapy 2006.

Subanalysis of initial trial, but with baseline FSFI score less than 26.5 (sexual dysfunction)

• 6 mo: greater improvement in active vs. sham - Sexual arousal - Lubrication - Orgasm - Sexual desire

Krychman. Jourrnal of Sexual Medicine. 2018

• FDA approval of its investigational device exemption (IDE) – 3/2018 • RCT, double-blinded, and sham controlled trial • Planned 250 pts, 25 sites • Active vs sham, 1:1 • Change in FSFI at 12 months • Safety/efficacy over 12 mo

• Salvatore et al – 2015 – 77 women with atrophy – Rx with CO2 laser – 12 weeks: • Increased FSFI overall score and in each domain • 85% regained sexual function – No placebo arm or estrogen arm – Selection bias – Short f/u

Salvator et al.. Climacteric 2015.

• ThermiVa (RF): – Multiple, prospective small case series – 3 treatments (interval 4-6 wks)

– Self reported laxity, vaginal atrophy, and sexual function improved – No AE - no placebo or validated outcomes

Alinsod. Lasers Surg Med 2016. Leibaschoff et al. Surg Technol Int 2016. © UNIVERSITY OF UTAH HEALTH Prolapse

• Bizjak-Ogrinc et al – 2013 • 28 pts – grade 2-4 cystocele • Rx with 1- 3 Er:Yag laser

• 6 mo outcomes: – 96.4% reduced POP by 1 grade – 42.9% by 2 grades – 7.1% by 3 grades

Bizjak-Ogrine et al. IUGA Poster 2013.

• Bizjak-Ogrinc et al – 2017 • 83 pts - grade 2–4 cystocele • Rx with 2-7 Er:Yag laser

• 12 mo outcomes: – Grade reduced to 0.86 from 2.36 – No AE, satisfaction high

Bizjak-Ogrine et al. Lasers Surg Med 2017.

• Thickens vaginal collagen to “prop” up the urethra

• ”shrinkage of vaginal canal & thickening of the vaginal wall”

Fotona et al. Climacteric 2015.

• 2015 - 2017 • Prospective cohorts • Indications: SUI, MUI, OAB

• 19 – 175 subjects • Erbium:YAG & CO2

• F/U range: 1 – 24 mo (6 mo)

Bhide et al. International Urogyn Journal. 2018

• Outcomes: – Decreased UI based on questionnaires • 1, 3, 6 mo f/u – High satisfaction rates (66%) – No adverse events reported

– Majority of studies with Er:YAG laser – No placebo/control groups

• Ogrinc – 2015 – 175 women, MUI

– Er:Yag laser • 3 sessions (0, 6 wks, 6 mo) • 3 (device passes) • Improvement in all incontinence severity index at 12 mo

Ogrinc et al. Lasers in Surgery & Medicine. 2015

• Gambacciani – 2018 – 114 subjects, SUI – Er:YAG laser • 3 sessions (30 days apart) • Outcomes: – ICIQ-SF decreased at 12 mo s/p Rx – ICIQ-SF no different than baseline at 18 & 24 mo – 84% requested re-Rx

• Schachar – 2018 – 1 year prospective cohort, 15 pts – No difference in SUI after Rx

Schachar. AAGL plenary presentation. 2018.

• Ex-vivo studies: – Increased storage of glycogen in epithelium – Fibroblast activation – Increased extracellular matrix – Restoration of vaginal ph

Zerbinati et al. Lasers Med Sci. 2015

• Samuels et al – 2018

• 40 postmenopausal pts

– Rx x 3 with CO2 laser intra/extra vaginally

– Vaginal bx: pre, 3 & 6 mo • VHI improved • Histology – Inc collagen & elastin staining, thicker epithelium

Samuels et al. Aesthetic Surgery Journal. 2018.

• Salvatore et al – 2014 – 50 women with atrophy – 3 Rx with fractional CO2 laser – 12 weeks: • Vulvovaginal atrophy symptoms • Vaginal health index (VHI) scores

Salvatore et al. Climacteric 2014.

• Perino et al. – 48 subjects, postmenopausal – 3 Rx fractional CO2

– 30 days: • VHI improved • Vaginal dryness • Burning/itching • Dyspareunia

Perino et al. Maturitas. 2015.

• Perino et al. – 48 subjects, postmenopausal – 3 Rx fractional CO2

– 30 days: • VHI improved • Vaginal dryness • Burning/itching • Dyspareunia

Perino et al. Maturitas. 2015.

• Sokol – 2017 – 30 pts – 3 Rx with fractional CO2

– Outcomes: 12 mo • Improved VAS (dryness, pain, burning, itch, etc) • Improved VHI • Improved FSFI • Improved elasticity via dilator size • 92% satisfied or extremely satisfied

Sokol. Menopause 2017.

• VELVET Study – Comparison of vaginal laser Rx to vaginal E2 in women with GSM – 6 mo data: • VAS vaginal dryness score improved in both groups, no difference • 70-80% patient satisfaction in both groups, no difference • 10 AE – VB, pain, discharge, breast tenderness, UTI, migraine, abd cramping

Paraiso et al. AUGS 39th Annual Meeting, October 2018

• “growing number of manufacturers marketing “vaginal rejuvenation” devices…claiming to treat symptoms related to menopause, urinary incontinence or sexual function.”

• “These products have serious risk and don’t have adequate evidence to support their use”

• “Deeply concerned women are being harmed…deceptive marketing of a dangerous procedure with no proven benefit, including women who’ve been treated for cancer, is egregious.”

• ACOG – May 2016 – CO2 fractionated laser listed no specific indication – Reaffirmed in July 2018

• AUGS – August 2018 – “Not pro-laser, or anti-laser; AUGS is pro- science” – “Not all therapies should be withheld from patients until Level 1 evidence is available; but we need to be honest with out patients”

• SOGC 2018 – No. 358: Intravaginal Laser for GSM & SUI – Histologic evaluation has shown similar short-term improvement in vaginal maturation in post-procedural vaginal biopsies with the use of intravaginal laser as seen with local estrogen (moderate). – Short-term observational studies of small patient number with the use of intravaginal laser have demonstrated reductions in symptoms (dryness, burning, itching, dysuria, and dyspareunia) and improvement in sexual satisfaction indices (low). – Short-term observational studies of small patient number with the use of intravaginal laser have demonstrated improvements in SUI (low).

© UNIVERSITY OF UTAH HEALTH CO2 LASER STUDIES Observational study (N = 50) on After 3 Tx over 12 wk a significant (P < .001) improvement of Mild events vulvovaginal atrophy17 vulvovaginal atrophy symptoms and VHIS scores was noted. Prospective study N = 77 3 Tx at 12 wk vulvovaginal atrophy symptoms and sexual Mild events postmenopausal women.22 function had significantly improved. Clinical evaluation included 48 patients At 30 d follow-up, significant improvements in vaginal No with vulvovaginal atrophy20 dryness, burning, itching, and dyspareunia (P < .0001) were demonstrated Clinical evaluation23 Stress urinary incontinence symptoms improved together No with tissue structure of the anterior vaginal wall under the mid-portion of the urethra. Clinical research study (N = 50)21 Vaginal biopsies on n = 50 with VVA changes and symptoms No at baseline and at 2 mo showing signs of remodeling after treatment. Controlled comparative study.18 N = 40 Fractional laser with local administration of platelets rich No plasma and pelvic floor exercise. The study group underwent PRP, CO2 laser, and pelvic exercise, whereas only PRP and pelvic exercise were applied to the control group. In the study group, histological evidence of vaginal mucus improvement and sexual function was shown.

Comparative study.24 One group was treated with Er:YAG laser at 2.940-nm and More mild events in the the results were compared to a group treated with CO2 laser CO2group. at 10.600 nm. Improvement in vaginal tightening was observed in both groups.

Gold et al. J Cosmet Dermatol. 2018

© UNIVERSITY OF UTAH HEALTH ER:YAG LASER STUDIES Two clinical evaluations (a) N = 135 and (b) (a) At 1 mo after treatment, 90.4% (n = 122/135) scored improved and 9.6% wanted a No N = 27.12 second session. At 3 and 6 mo all scored improved. (b) MFSQ average improvement of 8.5 points (36 point scale), tightening ranging from 3% to 28% and an average shrinkage of 17% (12 mm). Pilot study on N = 1712 Before and after treatment PISQ-12 was scored. Follow-up at 1 and 3 mo showed an Mild l burns (n = 1) average in PISQ-12 of 2.4 points. After 1 mo perineometric measurements were significantly higher (P < .028). N = 7314 Single treatment evaluated (ICIQ) at 1 and 2-6 mo. Significant improvement at 2-6 mo Mild vulvar edema (12 (6-16) vs 7 (0-13); P = <.001). Clinical evaluation on N = 3212 Interviews of both patient and partner at 1, 2, and 4 mo after treatment. At 4 mo, No 96% of partners reported an excellent/good improvement. Pilot study on N = 2111, 12 Two treatments with an interval of 15-30 d. Before and after PISQ-12 and POP-Q No scores at 3 mo. Patients and partners completed LVT questionnaire. 95% of patients and 85% of partners noted a strong/moderate improvement. POP-Q measurements: 5/21 had prolapses (stage 1-3). All had improved after 1 session. Pilot N = 2912 FSFI prior to treatment and after 21 d post-treatment. 16/21 Patients received 2 No treatments. Subjective improvement was noted in 96.6% of cases. IFSF total scores were significant (P < .05). Prospective study (a) N = 45 and (b) N = 1913 Both studies used once per month treatments for 3 mo. (a) Comparing laser with No standard treatment for GSM a significant decrease in vaginal dryness and dyspareunia (P < .01) was observed and a significant (P < .01) increase in VHIS. (b) Significant (P < .01) improvement of ICIQ-SF scores. Comparative study in GSM14 After treatment significant decrease in vaginal dryness and dyspareunia was No observed. Clinical evaluation N = 115 patients with SUI After 1 session, n = 62 (89.6%) had mild SUI and N = 29 (76.3%) of patients with No (n = 77 mild, n = 37 moderate and 1 moderate SUI were healed. At 1 mo after the 2nd session, 6/8 patients with mild SUI severe)12 and 5/9 with moderate SUI were healed. Pilot N = 39 had SUI12, 16treatment. ICQI-UI questionnaire before treatment and at 1 and 3 mo after treatment. Significant No (P < .002) ICQI-UI scores. Clinical evaluation on N = 2812 At 1 mo after treatment, 87% had improved and 17% reported no changes. At 3 mo, No 6% reported no change, all others had improved. Pilot in N = 9 with SUI and 4 requesting Before and after POP-Q, PISQ-12, and ICIQ-UI. The SUI patients all improved after No tightening.12 treatment as well as the patients who were treated for tightening. Clinical evaluation15N = 175 2Tx at 2-months intervals. Evaluations at 2, 6, and 12 mo. Of the patients, 77% had a No significant improvement and 34% exhibited mild urinary incontinence at the 1-year follow-up. © UNIVERSITY OF UTAH HEALTH RF STUDIES Transmucosal controlled Prospective randomized controlled trial 1 Tx every 30 d for 3 mo used for both arms. Evaluations using No radiofrequency heating device (N = 20): vaginal function (n = 10) and VHI, ICIQ-UI SF, UDI-6, IIQ-7, VAS. Punch Biopsies taken at the urethral muscle tone (n = 10)25 urethra- vesical junction in the anterior compartment, before and at the end of the treatment protocol. Basic and histochemical staining was used for analysis. Marked improvements in the treatment groups for all parameters. Prospective study N = 23 with 3 TX with a 4-6 wk interval. Endpoint temperature range of No mild-moderate vaginal laxity and SUI26 40-45°C for 3-5 min per zone during a total of 30 min treatment. Statistically significant improvements based on Vaginal Laxity Questionnaire and Sexual Satisfaction Questionnaire outcomes were shown. Improvements in stress incontinence, atrophic vaginitis, and orgasmic dysfunction were also observed. Single center, prospective study (N = 25)32 The transcutaneous temperature-controlled radiofrequency No device was used for treating orgasmic dysfunction. Twenty-three of 25 patients reported an average reduction in time to orgasm of 50% as well as tightening effects, vaginal moisture improvements, and improved sensitivity of the vulva and clitoris. The clinical data correlates with histopathology data. 2 Cryogen-cooled monopolar Pilot study N = 2427 1 Tx with reverse thermal gradient RF energy (60-90 J/cm ). None radiofrequency Self-reported vaginal tightness improved in 87% at 6 mo. Mean reported sexual function scores improved from 27.6 +/− 8.7 to 32.0 =/− 3.0 at 6 mo. All reported sustained improvements on SSQ at 6 mo after treatment (P = .002) 2 Prospective single-arm study N = 3028 1 TX at 90 J/cm during 30-min. Significant improvement in No sexual function at 6 mo (mean FSFI scores improved from 22.4 +/− 6.7 to 26.0 +/− 5.8 [P = .002]) was observed and was sustained through 12 mo 2 Randomized, placebo-sham-controlled, 1 TX at 90 J/cm during 30-min. Vaginal laxity was improved by Similar blinded, multi-center study N = 17424 43.5% and 19.6% (P = .002) in the active and sham groups, levels respectively. Differences in favor of active treatment vs sham reported in were shown in FSFI and FSDS-R total scores of 1.8 (P = .031) both active and −2.42 (P = .056), respectively and sham © UNIVERSITY OF UTAHtx groups HEALTH CLINICALTRIALS.GOV ClinicalTrials.gov Search Results 01/10/2019

Title Status Study Results Conditions Interventions Locations 1 Vaginal CO2 Laser and the Genitourinary Syndrome of Not yet recruiting No Results Available •Vaginal Atrophy •Device: Microablative Fractional CO2 laser Menopause 2 Vaginal Laser Therapy in Breast Cancer Survivors Recruiting No Results Available •Genitourinary Syndrome of Menopause •Device: Microablative Fractional CO2 Laser •Urogynecological Unit of Alexandra Hospital, Athens, Greece Therapy •Vaginal Atrophy •Breast Cancer •Dyspareunia 3 Laser Therapy in Managing Vaginal Prolapse Recruiting No Results Available •Cystocele •Device: Erbium Yttrium Aluminum Garnet •Urogynecological Unit of Alexandra Hospital, Athens, Greece (Er:YAG) laser •Vaginal Vault Prolapse •Rectocele •Enterocele 4 Laser Therapy Following Radiotherapy for Gynecological Recruiting No Results Available •Pelvic Radiotherapy •Device: Microablative Fractional CO2 Laser •Urogynecological Unit of Alexandra Hospital, Athens, Greece Cancer Therapy •Gynecological Cancer •Dyspareunia •Vaginal Dryness 5 Factors Affecting Therapeutic Efficacy of Vaginal Laser Recruiting No Results Available •Laser Thermotherapy, Stress Urinary •Procedure: Vaginal laser thermotherapy •Department of Obstetrics and Gynecology, Far-Eastern Therapy for Female Stress Urinary Incontinence, and the Incontinence Memorial Hospital, New Taipei, Banqiao, Taiwan Effect of Vaginal Laser Therapy on Overactive Bladder Syndrome and Sexual Function 6 Laser Therapy for Treatment of Urogenital Symptoms in Recruiting No Results Available •Genitourinary System; Disorder, Female •Device: fCO2 Laser Therapy Group •Beaumont Hospital, Royal Oak, Michigan, United States Women •Burning Vagina •Dyspareunia •Irritation; Vagina •Menopause Related Conditions •Urinary Incontinence •Urinary Bladder, Overactive •Urinary Tract Infections •Lichen Sclerosus •Stress Urinary Incontinence 7 Laser Vaginal Treatment for SUI Recruiting No Results Available •Stress Urinary Incontinence •Procedure: Erbium-YAG laser vaginal •Sunnybrook Health Sciences Centre, University of Toronto, treatment Toronto, Ontario, Canada 8 Randomized, Controlled Trial With Hybrid Fractional Laser Recruiting No Results Available •Vaginal Atrophy, Sexual Dysfunction, •Device: Hybrid Fractional Laser •Miamim Dermatology, Miami, Florida, United States Vaginal Dryness, Dyspareunia 9 Vaginal Elasticity Assessment Before and After Vaginal Recruiting No Results Available •Laser Burn •Diagnostic Test: Vaginal Tactile Imaging •Rambam health care campus, Haifa, Israel Carbon Dioxide Laser Treatment. 10 Laser Therapy for Vulvovaginal Symptoms in Breast Cancer Recruiting No Results Available •Vulvovaginal Atrophy •Device: CO2 Fractional Ablative Laser •Royal North Shore Hospital, Saint Leonards, New South Wales, Patients Australia •Genitourinary Symptoms and Ill-Defined •Device: Placebo Conditions •Sydney Adventist Hospital, Wahroonga, New South Wales, Australia

- Page 1 of 2 -

• Energy-based devices are in the early stages of validation/safety monitoring • Well designed studies are needed – Short term, case series, non-validated scales/outcomes – strict inclusion/exclusion criteria, placebo • Standardized training – Who? Cost? What? • Alternatives discussed