Vaginal CO2 Laser for Stress Incontinence: A Randomized Controlled Trial
Phase: NA
Conditions: Stress Incontinence Female, Laser
Sponsor: Hvidovre University Hospital

Vaginal CO2 Laser for Stress Incontinence: A randomized controlled trial (1) 
 
Trial registration: to come at clinical trialgs.gov 
 
 
27.01.2019 
Funding: Hvidovre hospital. The funder has no role in study design, data collection, data analysis, 
data interpretation, or writing the report 
 
Written by: Benny Kirschner, Josephine Obel and Jeppe Bennekou Schroll 
 
 
This protocol has been developed in accordance with the SPIRIT guidelines. Numbers referring to 
requirements from Danish Ethics Committee has been written in parenthesis.  
 
 

 
 
Introduction (2) 
Urinary incontinence (UI) is a common condition affecting nearly 50% of women at some point in their life 
(MinassianVA, Obstet Gynecol. 2008).  The prevalence is increasing with age and is often a great burden for 
the patient with serious implications on the quality of life (Schreiber, ACTA 2017). Studies report that only 
25% of affected women seek help for their incontinence symptoms and of those, less than half receive 
treatment (MinassianVA, Int Urogynecol J. 2012). UI is typically divided into 3 main types, namely (i.) stress 
urinary incontinence (SUI), which affects up to 30% of women (Ogah, Neurol. and uro., 2011) and is 
characterized by involuntary loss of urine with increases in intra-abdominal pressure such as exercise and 
coughing, (ii.) urgency incontinence, which is characterized by a sudden compelling desire to pass urine that 
is difficult to defer (Abrams, Neurolourol. Urodyn, 2010) and (iii.) mixed urinary incontinence, where 
symptoms of both stress and urgency incontinence are found. SUI is caused by poorly functioning urethral 
closure and is characterised by loss of anatomic support in the pelvic area. This anatomic defect can be 
caused by multiple pregnancies, vaginal childbirth, obesity and repetitive increase in intra-abdominal 
pressure, such as seen in chronic obstipation or coughing, heavy lifting and high-impact exercise  (HandaVL, 
Obstet Gynecol. 2011//  HandaVL, Am J Obstet Gynecol. 2004 //LawrenceJM, Diabetes Care. 2007// 
Nygaard IE, Am J Obstet Gynecol. 2016). Urgency incontinence is typically idiopathic although it is also seen 
in women with general neurologic disorders, such as Parkinson disease, multiple sclerosis and pelvic or 
spinal nerve injury.  
 
Initial treatment of urinary incontinence typically starts with non-invasive measures, due to the 
fact that related benefits are associated with low risks and limited expenses. These measures include 
lifestyle modifications, such as weight loss, smoking cessation, treatment of obstipation, alcohol- and 
caffeine-restriction, avoidance of excess fluid intake and fluid- and voiding-management. Systematic reviews 
report that pelvic floor exercises in women with IU are beneficial (Hay-Smith EJ Cochrane Database Syst 
Rev. 2011). A systematic review found that 59% of women with stress urinary incontinence were cured after 
12 months of supervised pelvic floor muscle training. (RiemsmaR,HagenS, BMC Med. 2017). 
Treatment of SUI aims at strengthening the pelvic floor and stabilize urethral mobility. Non- 
invasive treatment of SUI includes pelvic floor muscle training and use of vaginal devices. There are studies 
that indicate that bladder control pessaries are effective and may be preferable for women, who have SUI 
during specific situations as for example, during exercise (Lipp A,Cochrane Database Syst Rev 2014.)  
Furthermore, there are over-the-counter vaginal devices, such as Contrelle® or Impressa® that are SUI 
specific, and may be better tolerated as they are easier to self- administer. Women with symptoms of SUI in 
spite of conservative non-invasive treatment may be candidates for surgery. Currently, the most commonly 
performed surgery for SUI is the midurethral sling, a 30-minute outpatient procedure in which a synthetic 
mesh sling is placed through either a retropubic or transobturator approach. (Nager CW. Am J Obstet 
Gynecol. 2016). The midurethral sling is the most extensively studied procedure for SUI, with documented 
short-term efficacy (>5 yrs.) between 43- 92% (Ford AA,RCochrane Database Syst Rev. 2015//  Schimpf 
MO, Am J Obstet Gynecol. 2014). Complication rates of this procedure is low, but includes risk of bladder- or 

urethral lesion, urinary retention, haematoma, pain, worsening of urgency, dyspareunia and sling erosion 
(Ford AA,RCochrane Database Syst Rev. 2015// Morling JR, Lancet. 2017// Anger JT, Urology. 2014)  
  
A novel minimal-invasive method of treating UI, has been introduced in the recent years, namely vaginal 
laser treatment. The use of laser has now been described in pelvic organ prolapse, UI and genito-urinary 
symptoms of menopause. Bhide et al have recently published a review article, where they describe 5 
prospective cohort studies of laser-reatment of SUI (Table 1) (Bhide AA, Int. Urogyn. Journ., 2018). 
Gambacciani et al. published a study of 45 women with IU, of whom 19 had SUI (Gambacciani M, Ital J 
Gynaecol Obstet. 2015). Vaginal treatment included application of YAG laser 3 times with 1 month apart and 
symptoms were evaluated at baseline and at a 3- and 6-month follow-up with ICIQ-UI SF questionnaire. The 
treatment induced a significant decrease in ICIQ-UI at 3 months with decrease of ICIQ scores from 12.0+/-
1.8 to 5.6+/-2.6 and this was still significant at 6 months. Ogrinc et al published a study on the use of YAG 
laser on women with IU, of whom 115 had SUI. Symptoms were evaluated at baseline and at 12-months 
follow-up with Incontinence Severity Index (ISI) and all women showed significantly decreased ISI scores 
(Ogrinc UB, Lasers Surg Med. 2015). Fistonic et al published two studies of the use of a single application of 
YAG laser in the treatment of SUI and evaluated with ICIQ-UI SF. The first study evaluated 31 women with 
SUI and follow-up at 1- 2- and 6- months showed significantly reduced ICIQ-IU SF scores albeit many of 
women were lost to follow-up (Fistonić N., YAG. Lasers Med. Sci. 2016). The next study of 73 women with 
SUI showed 72.3% experiencing improvement of symptoms, 23.4% experiencing no change and 4.3% 
experiencing worsening (Fistonić N, Climacteric. 2015). Pardo et al. evaluated the vaginal erbium:YAG laser 
in a longitudinal prospective study in 42 patients with SUI (Pardo JI, Eur J Obstet Gynecol Reprod Biol. 
2016). Treatment was applied twice with 21- 28 days apart and median ICIQ-IU SF scores, which was 
reported at 3- and 6- months follow-up, was significantly reduced; 78.6% reported improvement of SUI and 
38.1% reported a complete remission of SUI. Gambacciani et al. studied 205 post-menopausal women of 
which 114 were diagnosed with SUI. In this study, three vaginal erbium:YAG laser applications were 
administered at 30-day intervals, and ICIQ-SF was used to evaluate before and after treatment with follow-
up up to 24 months post treatment (Gambacciani M, Climacteric. 2018). The results demonstrated a 
significant decrease in ICIQ-SF scores from baseline to 12 months post treatment. However, at 18 and 24 
months, ICIQ-SF scores were not significantly different from baseline. All 5 studies used a non-randomised 
selection of patients and treatment effect was estimated by using pre-treatment incontinence scores for 
comparison . Only the YAG laser has been evaluated in a randomized trial with 114 women which found 
significant improvement in the ICIQ-SF scores in the treatment arm compared with placebo (Bleganje 2018). 
None of the mentioned studies showed any serious complications or side effects of the laser treatment.  
 
The FDA has recently pointed out that there is a lack of evidence of efficacy and safety of 
vaginal laser in the treatment of urogenital symptoms in women   
(https://www.fda.gov/medicaldevices/safety/alertsandnotices/ucm615013.htm). Of this reason, it is important 
to investigate this type of treatment in controlled, protocol-based studies, before general use is disseminated.  
Vaginal laser is a relatively new approach in the treatment of women with SUI. The treatment has shown 
promising results, and only the YAG laser has been evaluated in a randomized trial (Blaganje 2018).  

Furthermore, many of the earlier studies have been supported by the private sector and so sceptics will 
claim that there is a potential of biased results (Conte C, Journal de l'Association francaise d'urologie et de la 
Societe francaise d'urologie. 2017). It is important that all new treatment-regimes in the public health care 
are tested and compared to existing regimes and placebo, not only medical drugs.  
 
Transvaginal treatment with the MonaLisa Touch laser system has been shown to be safe and without major 
complications or side effects, when used in women with vaginal atrophy. The system is thought to work by 
stimulating growth and remodelling of collagens in the vaginal support tissue. Furthermore, it is assumed, 
that intravaginal laser treatment can stimulate the growth of urethral collagen, thereby reducing urethral 
mobility and increasing intraurethral pressure, and so should potentially reduce symptoms of SUI. 
 
Our aim with this study is to determine if transvaginal CO2 laser- treatment (DEKA SmartXide2 Laser 
System, MonaLisa Touch), renders significant effect in women with SUI. To best test this hypothesis, the 
study will be performed in a prospective, randomised controlled fashion in our institution. We will measure 
the effect as patient reported improvement using a validated scale as well as an objective measurement.  
 
 
Methods (3) 
Study setting 
Patient will be included from our hospital (a Danish academic hospital) among women referred with 
incontinence. Eligible patients will be randomized to either laser treatment or “sham” laser treatment. 
 
Eligibility criteria (5) 
The study will take place in the department of Gynecology and Obstetrics of Hvidovre University Hospital, 
Copenhagen Denmark in the period of May 2019 to May 2020. Inclusion criteria for the study cohort and 
controls will be patients i. referred from specialist gynecologists or GPs with SUI; ii. speak and understand 
Danish; iii. has a voiding diary that indicates stress incontinence; iv. older than 18 years of age; vii. with BMI 
under 35; viii. and present with mild to severe SUI evaluated after ICIQ-SF (slight (1-5), moderate (6-12), 
severe (13-18) and very severe (19-21), Klovning 2009). Exclusion criteria presence of pelvic organ prolapse 
greater than stage II by the POP-Q system, previous pelvic surgery, current infections, keloid formation, 
vaginal pain, dyspareunia and ongoing pregnancy. 
 
Interventions 
In this study, women will receive a series of three treatments using a fractional (pulsed) CO2 laser system 
(SmartXide2 MonaLisa Touch, DEKA M.E.L.A Srl, Florence, Italy), each performed in an outpatient setting 
without analgesia. A tubular laser-probe is inserted in the vaginal canal until reaching the vaginal vault.  A 
burst of laser pulses is transmitted through the probe and deflected at 90° in four directions towards the 
vaginal wall, then rotated 45° for a second burst of pulses. Guided by markings on the probe, it is withdrawn 

4mm and the procedure is repeated until reaching the introitus. Treatment parameters include power 30W, 
dwell time 1000µs, 1000µm spacing, using normal scan mode, with Smartstack setting for 1 at first 
application and 3 for the next two applications.  
Both study- and placebo- treatments will be performed by specialist gynecologists employed in the 
department. Patients, who meet inclusion criteria and consent to study participation, will be randomized by 
computer service [REF] to conservative treatment, which encompass local estrogens (Vagifem 10µg twice 
weekly) if relevant (postmenopausal women) and pelvic floor training supervised by specialised 
physiotherapists in our own institution, whilst the study cohort will receive the same treatment with the 
addition of transvaginal laser applied thrice with 25- 45 days apart (CO2 laser- treatment (DEKA SmartXide2 
Laser System, MonaLisa Touch). The controls will receive placebo treatment, with the use of the inactive 
laser, but relevant sound effects. 
 
Outcomes 
Primary outcome of the study is patient experienced improvement of SUI evaluated by standardized ICIQ-SF 
questionnaire.  
Our secondary outcome is objective improvement as measured by standardized stress test performed by 
specialist nurse before treatment and 1-2 month after last laser or placebo treatment. The bladder is emptied 
with a catheter and 300ml of saline is inserted. The patient is then stood up wearing a pad with legs slightly 
apart and asked to forcefully cough 3 timers. The examiner registers whether there is incontinence as either 
yes or no as well as grams of urin leakage in the pad. Furthermore, side- effects both positive and negative 
as well as patient satisfaction will be registered by the use of patient questionnaires at 1-2 months post 
treatment.  
 
Participant timeline 
Timeline after inclusion 
• 
1st visit in outpatient clinic: evaluation by nurse or physician; instruction in minimal care treatment, 
pelvic examination, evaluation of bladder diary, evaluation of study eligibility and randomization. 
Baseline information registered in case report form and referral to physiotherapy. 
• 
2nd visit. 1st Laser/placebo treatment  
• 
3rd visit 2nd Laser/placebo treatment (between 20 and 40 days after previous treatment) 
• 
4th visit 3rd Laser/placebo treatment (between 20 and 40 days after previous treatment) 
• 
5th visit. Follow up 1-2 months after last treatment. ICIQ-SF questionnaires, clinical examination and 
standardized stress test. Information registered in case report form. 
Both study-cohort and controls will receive pelvic floor training supervised by specialised physiotherapists. If 
the treatment is evaluated as unsuccessful, next treatment option will be considered. 
 
4. Sample size 

Based on variation and observed effect of more than 2 points from other studies (Blaganja 2018) on the 
ICIQ-UI SF scale we have calculated that 20 patients in each group would be sufficient even with 20% 
dropout to show a difference. The assumptions are significance level of 0,05 and a risk of type 2 error set to 
20%. 
 
Recruitment 
All urogynecologist and specialised urogynecological nurses at the department will be actively involved in the 
study and will be actively including patients. 
 
Methods: Assignment of interventions (for controlled trials) 
Sequence generation 
A computer till generate the numbers using blocks of 6. 
 
Allocation concealment mechanism 
Allocation will be hidden in a computer program. 
 
Implementation 
The data manager will do the sequence generation. Doctors at the urogynecological clinical will enroll 
patients and assignment will occur when patient data is submitted in the electronical case report form. 
 
Blinding (masking)  
The patient and the outcome assessor (nurse) will be blinded. However, the doctor performing the laser 
treatment cannot be blinded. 
Unblinding will occur if a patient suffers adverse events that requires treatment or exclusion of the trial. 
 
Methods: Data collection, management, and analysis 
Data collection methods 
Baseline data will be recorded: age, BMI, parity, ICIQ-UI SF, standardized stress test, degree of pelvic 
prolapse. All data will be saved in RedCAP, which will provide facilities for randomization as well as ensure 
that data are being stored according to Danish legislation.  
ICIQ-UI SF is a validated scale for measuring degree of stress incontinence and has been used in many 
studies.  
Data collection forms will be constructed in RedCap. 
Both the study cohort and controls will be contacted by telephone, if they do not come for follow-up treatment 
or data-collection.  
Nurses will be instructed in the standardized stress test. 
 
Statistical methods 

The post treatment scores will be compared using Students t-test for the primary outcome and chi square 
test for dichotomous outcomes. Our strategy is an intension to treat analysis when possible.  
Clinically significant differences of our primary outcome is probably at least 2 points. 
 
Methods: Monitoring (6) 
Data monitoring 
All investigators will be part of the monitoring board and will decide whether the trial should be terminated. 
No interim analysis are planned due to the few patients involved.  
 
Harms 
All harms will be reported verbatim. Serious adverse events will be discussed by the monitoring board within 
two work days. 
 
Auditing 
No auditing is planned as the procedures and measurements will be carried out be very few health workers. 
 
Ethics and dissemination 
Research ethics approval 
Relevant approvals from ethics committee and data protection agency will be obtained.  
 
Protocol amendments 
Protocol amendments will be reported to ethics committees and trial registries. 
 
Consent or assent (12) 
Written and oral consent will be obtained and documented recruiting gynaecologist or specialized nurse in 
the outpatient clinic. At the clinic patients are attended individually in a separate room. If they are interested 
they will be scheduled for treatment. In the mean time they can consult with their doctor or family.  
 
Confidentiality 
Data will be collected, stored and reported in accordance with Danish legislation and approval from the data 
protection agency will be obtained. 
 
Declaration of interests 
All investigators will have to provide a declaration of interest before the study begins. Investigators with 
conflicts to the manufacturer of the Laser device will not be able to participate in this study. 
 
Access to data 
Only investigators will have access to data. Data will either be anonymized or destroyed a few years after the 
study finishes.  

 
Ancillary and post-trial care (11, 15) 
As this treatment is already being used in Denmark, patients that suffer damage will be eligible to 
compensation through the ‘Patienterstatningen’. 
No participation fee for participant will be given. 
 
Dissemination policy (13) 
Results will be reported in peer reviews journals and the study results will be registered at clinicaltrials.gov. 
Professional writes will not be used. We will share our data to the extent it does not interfere with privcacy 
and Danish legislation.  
 
Economy (10) 
Hvidovre hospital has so far funded the project with 60.000. The project has been initiated by the authors of 
the protocol. Additional funding will be sought to employ a PhD student for managing data, doing analyses 
and writing the paper. The department will pay for salary of the nurses and treating physicians and the Laser 
is already at our institution. 
 
Additional information to Danish ethics committee 
 
7. Biological material 
No biological material will be collected 
8. Information from patient charts 
We will ask patients permission to look up weight, height, medicine and prior illnesses from their chart. We 
will also ask permission to look up admission 12 months following last treatment. This is required to monitor 
adverse events. 
9. Handling of patient information 
All patient data will be safely stored in accordance with Danish legislation. Approval from the data protection 
agency will be obtained. 
14. Research ethics 
The treatment has already been introduced at several hospitals and private clinics and the risk is considered 
acceptable. Future patients could potentially avoid a surgical procedure that is associated with 
complications.  
 
References 
MinassianVA,StewartWF,WoodGC.Urinary incontinence in women: variation in prevalence estimates and risk factors. Obstet Gynecol. 
2008;111 (2 pt 1):324-331.  
 
MinassianVA,YanX,LichtenfeldMJ,SunH, Stewart WF. The iceberg of health care utilization in women with urinary incontinence. Int 
Urogynecol J. 2012;23(8):1087-1093.  
 

AbramsP,AnderssonKE,BirderL,etal; Members of Committees; Fourth International Consultation on Incontinence. Fourth International 
Consultation on Incontinence recommendations of the International Scientific Committee: evaluation and treatment of urinary 
incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol Urodyn. 2010;29(1):213-240.  
 
HandaVL,BlomquistJL,KnoeppLR,Hoskey KA, McDermott KC, Muñoz A. Pelvic floor disorders 5-10 years after vaginal or cesarean 
childbirth. Obstet Gynecol. 2011;118(4):777-784.  
 
HandaVL,HarveyL,FoxHE,KjerulffKH.Parity and route of delivery: does cesarean delivery reduce bladder symptoms later in life? Am J 
Obstet Gynecol. 2004;191(2):463-469.  
 
LawrenceJM,LukaczES,LiuIL,NagerCW, Luber KM. Pelvic floor disorders, diabetes, and obesity in women: findings from the Kaiser 
Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007;30(10): 2536-2541.  
 
NygaardIE,ShawJM.Physicalactivityandthe pelvic floor. Am J Obstet Gynecol. 2016;214(2):164- 171.  
 
Hay-Smith EJ, Herderschee R, Dumoulin C, Herbison GP. Comparisons of approaches to pelvic floor muscle training for urinary 
incontinence in women. Cochrane Database Syst Rev. 2011;(12): CD009508.  
 
 
RiemsmaR,HagenS,Kirschner-HermannsR, et al. Can incontinence be cured? a systematic review of cure rates. BMC Med. 
2017;15(1):63.  
 
LippA,ShawC,GlavindK.Mechanicaldevices for urinary incontinence in women. Cochrane Database Syst Rev. 2014;12(12):CD001756.  
 
NagerCW.Midurethralslings:evidence-based medicine vs the medicolegal system. Am J Obstet Gynecol. 2016;214(6):708.e1-708.e5.  
 
FordAA,RogersonL,CodyJD,OgahJ. Mid-urethral sling operations for stress urinary incontinence in women. Cochrane Database Syst 
Rev. 2015;(7):CD006375.  
 
SchimpfMO,RahnDD,WheelerTL,etal; Society of Gynecologic Surgeons Systematic Review Group. Sling surgery for stress urinary 
incontinence in women: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014;211(1):71.e1-71.e27.  
 
Morling JR, McAllister DA, Agur W, Fischbacher CM, Glazener CM, Guerrero K, et al. Adverse events after first, single, mesh and non-
mesh surgical procedures for stress urinary incontinence and pelvic organ prolapse in Scotland, 1997-2016: a population-based cohort 
study. Lancet. 2017;389(10069):629-40.  
 
Anger JT, Khan AA, Eilber KS, Chong E, Histed S, Wu N, et al. Short-term outcomes of vaginal mesh placement among female 
Medicare beneficiaries. Urology. 2014;83(4):768-73.  
 
 
Alka A. Bhide , Vik Khullar, Stephen Swift & Giuseppe A. Digesu. The use of laser in urogynaecology. Internat. Urogyn. Journ., dec. 
2018.  
 
Gambacciani M, Levancini M. Vaginal erbium laser: the second generation thermotherapy for the genitourinary syndrome of menopause 
(GSM) in breast cancer survivors. A preliminary report of a pilot study. Ital J Gynaecol Obstet. 2015;27:N;1. 
 
Ogrinc UB, Senčar S, Lenasi H. Novel minimally invasive lasertreatment of urinary incontinence in women. Lasers Surg Med. 
2015;47(9):689–97. 

 
Fistonić N, Fistonić I, Guštek ŠF, Turina ISB, Marton I, Vižintin Z, et al. Minimally invasive, non-ablative Er:YAG laser treatment of 
stress urinary urinary incontinence in women—a pilot study. Lasers Med Sci. 2016;31(4):635–43. 
 
Fistonić N, Fistonić I, Lukanovič A, Findri G, Sorta Bilajac Turina I, Franić D. First assessment of short-term efficacy of Er:YAG laser 
treatment on stress urinary incontinence in women: prospective cohort study. Climacteric. 2015;18:37–42 
 
Pardo JI, Solà VR, Morales AA. Treatment of female stress urinary incontinence with erbium-YAG laser in non-ablative mode. Eur J 
Obstet Gynecol Reprod Biol. 2016;204:1–4. 
 
 Gambacciani M, Levancini M, Russo E, Vacca L, Simoncini T, Cervigni M. Long-term effects of vaginal erbium laser in the treat- ment 
of genitourinary syndrome of menopause. Climacteric. 2018;21(2):148–52.  
 
Conte C, Jauffret T, Vieillefosse S, Hermieu JF, Deffieux X. Laser procedure for female urinary stress incontinence: A review of the 
literature. Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie. 2017;27(17):1076-83. 
 
FDA. DEKA SmartTide Laser (MonaLisa Touch) approval letter FDA 2014. 2014.  
 
Klovning A, Avery K, Sandvik H, Hunskaar S. Comparison of two questionnaires for assessing the severity of urinary incontinence: The ICIQ-
UI SF versus the incontinence severity index. Neurourol Urodyn. 2009;28(5):411-5. doi: 10.1002/nau.20674. 
 
Blaganje M, Šćepanović D, Žgur L, Verdenik I, Pajk F, Lukanović A.  Non-ablative Er:YAG laser therapy effect on stress urinary 
incontinence related to quality of life and sexual function: A randomized controlled trial.  Eur J Obstet Gynecol Reprod Biol. 2018 
May;224:153-158. doi: 10.1016/j.ejogrb.2018.03.038. Epub 2018 Mar 22.  
 

 
 
 
Table 1.