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19
Non-ablative vaginal erbium YAG laser for the treatment of cystocele
Urska Bizjak Ogrinc1, Sabina Sencar1
1 Juna Clinic, Savska cesta 10, 1000 Ljubljana, Slovenia
ABSTRACT
Purpose: the aim of the study was to evaluate the effects
of Vaginal Erbium Laser (VEL), a non-ablative solid
state erbium-doped yttrium-aluminum-garnet crystal
(Er:YAG) laser treatment for reduction of prolapses.
Methods: in this prospective cohort study, 61 patients
with cystoceles of grades II–IV were submitted to 2-5
treatments with a nonablative VEL laser at 2-month
intervals. At baseline and 2, 6 and 12-month follow-
ups, prolapses were photographed and graded using
the Baden-Walker scale during a physical examination.
Patients were interviewed at each follow-up about
adverse effects and their satisfaction. Pain during
treatment was measured on a 10-point visual analog
scale (VAS).
Results: at baseline 40 patients presented with grade
II cystoceles, 15 with grade III and 6 with grade IV
cystoceles. At the nal follow-up, the grade of prolapse
was reduced by at least one grade in 95% of patients,
with 85% of patients presenting with grade 0 or I
prolapses and the remaining 15% of patients with grade
II prolapses. Most patients were either very satised
(57%) or satised (33%) with the treatment. Treatment
discomfort was low (0.5 VAS). No major adverse effects
were reported.
Conclusions: the results of this pilot study show that
the non-ablative VEL treatment may improve cystoceles
with minimal patient discomfort and no adverse effects.
If these preliminary results will be conrmed in a
properly designed, controlled study, then VEL could
be considered in selected cases as a minimally-invasive
alternative to surgery.
Keywords: pelvic organ prolapse, cystocele, Er:YAG,
non-ablative laser, non-surgical treatment
Corresponding author: Urska.Bizjak-Ogrinc@juna.si
Copyright 2017, Partner-Graf srl, Prato
DOI: 10.14660/2385-0868-59
Gyn ae c o l o g y & Obstetrics
Italian Journal of
March 2017 - Vol. 29 - N. 1 - Quarterly - ISSN 2385 - 0868
SOMMARIO
Scopo dello studio: scopo dello studio è stato quello
di valutare gli effetti del trattamento con laser vaginale
non ablativo Erbium (Vaginal Erbium Laser, VEL) nella
riduzione del prolasso genitale.
Metodi: in questo studio di coorte, prospettico, non
controllato, 61 pazienti con cistocele di II–IV grado sono
state sottoposte a trattamento con VEL, eseguendo da 2
a 5 trattamenti, ad intervalli di 2 mesi. La valutazione
del grado di prolasso è stata eseguita secondo la
classicazione di Baden-Walker, sia in condizioni
basali che dopo 2, 6 e 12 mesi, registrando le immagini
fotograche durante la visita, valutando anche
l’incidenza degli effetti collaterali e la soddisfazione
delle pazienti. Il dolore riferito dalle pazienti durante il
trattamento è stato valutato attraverso una scala visuo-
analogica da 0 a 10 (VAS).
Risultati: in condizioni basali 40 pazienti presentavano
un cistocele di II grado, 15 di III grado e 6 di IV grado.
Al follow-up nale, il 95% delle pazienti presentava
una riduzione del prolasso di almeno 1 grado; l’85%
delle pazienti presentava un prolasso di grado 0 o I,
e il rimanente 15% delle pazienti presentavano un
prolasso di II grado. Il dolore indotto dal trattamento è
stato basso (0.5 VAS). La maggior parte delle pazienti è
risultata molto soddisfatta (57%) o soddisfatta (33%) del
trattamento. Non sono stati riscontrati eventi avversi
durante lo studio.
Conclusioni: i risultati di questo studio pilota
suggeriscono che il trattamento con VEL possa
determinare un miglioramento del grado di cistocele,
inducendo minimi effetti collaterali. Se questi risultati
fossero confermati in studi controllati, il trattamento
laser potrebbe essere considerato in casi selezionati una
valida alternativa non invasiva alla chirurgia.
Parole chiave: prolasso genitale, cistocele, Er:YAG, laser
non-ablativo, trattamento non invasivo
It. J. Gynaecol. Obstet.
2017, 29: N. 1
20
Non-ablative laser treatment of cystocele
INTRODUCTION
Pelvic organ prolapse (POP) affects a large
proportion of middle-aged and older women,
with a prevalence of any degree of POP ranging
in different studies from 32% to 98%(1–3). POP is
a complex condition of pelvic floor dysfunction,
with many contributing factors such as vaginal
childbirth, aging, congenital conditions (e.g.
collagen defects), raised intra-abdominal pressure,
etc.(4). Many women with lower stage POP
are asymptomatic, with only 4-10% of women
reporting POP-related symptoms(5–7). Women with
symptomatic POP experience a sensation of vaginal
bulging or a visible bulge protrusion in higher POP
grades, with difficulties in sitting, walking, sexual
intercourse and many other everyday activities(4).
Although POP is not a life-threatening condition,
its symptoms have a severe impact on patients’
quality of life and wellbeing. POP also represents a
significant public health expense, being a frequent
cause for major gynecological surgery(4). Current
management options for POP include conservative
management, such as physical therapy and vaginal
pessaries, as well as various surgical procedures.
Vaginal pessaries have been in use for a long time
because of their low invasiveness(8,9). However,
their use is characterized by a high discontinuation
rate, mainly due to difficulties with inserting/
removing the pessary and side-effects, such as
infections, bleeding and pain(8,9).
Many patients with POP symptoms ultimately
undergo surgical treatment. The lifetime risk of
having prolapse surgery before the age of 80 is 11%,
with almost a third of patients needing repeated
procedures(10). Different surgical techniques are
currently used to treat POP(11). The methods of
choice depend on the type and the severity of
prolapse. In recent decades, transvaginal insertion
of polypropylene mesh implants has been one
of the most popular options, although they are
associated with a high rate of side effects(12).
Prolapse of the bladder into the anterior
vaginal compartment, or cystocele, is the most
frequent type of POP - roughly one third of POP
patients suffer from cystoceles(3). The anterior wall
of the vagina is a very important structure for
pelvic floor support, which provides a hammock-
like support to the upper-lying urethra and the
bladder(13). According to the integral theory of
Petros and Ulmsten, the connective tissue in the
anterior vaginal wall has an important role in
supporting the bladder. Vaginal laxity resulting
from childbirth trauma and aging-related collagen
degradation can cause the loss of support and
contractile strength of the pelvic floor muscles
that attach to the anterior vaginal wall. As a
consequence, stress urinary incontinence and/or
POP arise as typical symptoms of this pelvic floor
dysfunction(14,15).
Collagen is the connective tissue component
that is most responsible for robustness, stability
and plasticity of the vagina. Pulses of laser energy
that temporarily increase the temperature of
collagen can initiate neocollagenesis and improve
collagen structure(16,17). As a result of the laser-
induced temperature increase, intermolecular
cross-links that stabilize the collagen triple-helix
structure are broken, which leads to the shrinkage
of collagen fibrils and an improvement in tissue
firmness, followed by neocollagenesis. VEL
treatment was recently used in different studies
in order to achieve strengthening of the vaginal
wall for the treatment of SUI(18–21) and vaginal
relaxation(18,22).
In the present pilot study, we evaluated the
effects of VEL as a noninvasive, non-surgical
treatment for cystoceles.
MATERIALS AND METHODS
This was a prospective, single-center,
uncontrolled cohort pilot study. It was conducted
between March 2012 and November 2013 and
included 61 women older than 18 years of age.
The study was approved by the Ethical committee
of the Republic of Slovenia and was conducted
in accordance with the Declaration of Helsinki.
No financial incentives were proposed to the
participants.
During the first visit, the eligibility of the
patient was verified, a written informed consent
was obtained and sociodemographic and clinical
characteristics were collected. Inclusion criteria
for participation in the study were: the presence of
POP symptoms, diagnosis of cystocele of grade II
to IV according to the Baden-Walker scale, normal
PAP smear, negative urine culture and integrity of
the vaginal mucosa (without injuries or bleeding)
and voluntary informed consent. Exclusion criteria
were: previous POP surgery, pregnancy, intake of
photosensitive drugs, vaginal bleeding injuries or
infection in the treated area. All the consecutive
patients who presented at our clinic during the
recruitment period and met the inclusion criteria
(and did not meet the exclusion criteria) were
included in the study.
Laser therapy was performed using a 2940 nm
VEL (SP Spectro, Fotona, Slovenia) with SMOOTH
21
Non-ablative laser treatment of cystocele Urska Bizjak Ogrinc et al.
mode setting, which enables non-ablative,
thermal-only operation(18). The parameters were
selected based on extensive preclinical and clinical
studies(23–26). Briefly, Variable Square Pulse (VSP)
technology controls the energy and time duration
(or pulse width) simultaneously, reducing the
power and increasing the pulse duration. The
SMOOTH™ mode, with its sequence of low-
fluence longer-shaped Erbium pulses, distributes
the heat into the mucosa surface, achieving a
controlled, deep thermal effect without ablation.
Therefore, the Erbium SMOOTH™ mode pulses
allow controlled tissue heating in a safe and
harmless ambulatory procedure without ablation
or carbonization of the tissues, practically
avoiding the risk of perforation with accidental
lesions of the urethra, bladder or rectum. Each
laser treatment session consisted of a full vaginal
canal irradiation (using a 360° circular adapter),
followed by additional irradiation of the prolapsed
anterior wall (using a 90° angular adaptor) and
concluded with irradiation of the vestibule area.
Depending on the prolapse severity, multiple
passes of laser irradiation were applied, with
emphasis on the anterior wall irradiation. On
average, we used a total of 8 passes per session,
delivering in this manner around 1500 J of laser
energy to the vaginal mucosa. The VEL procedures
were performed in an outpatient clinical setting,
without any specific preparation, anesthesia, or
post-treatment medications. The treatment time
was approximately 15 minutes and the procedure
did not require any consumables.
Patients received 2-5 treatment sessions with
intervals of 2 months in between the sessions.
This time interval is sufficient to allow the
neocollagenesis initiated by the previous laser
session to proceed(27), and similar intervals were
used in previous studies using VEL(26). The effect of
the previous session can thus be seen and the need
for additional sessions correctly evaluated. At least
two treatments are deemed necessary to provide
long-term results. The total number of sessions
was dependent on the patients’ satisfaction with
the result (lack of symptoms) and the physical
examination after the 2nd session.
At baseline and at each follow-up visit, a
physical examination was conducted, prolapses
were photographed, and the prolapse stage was
determined in a restful and straining (achieved
by coughing) dorsal lithotomy by 2 physicians
according to the Baden-Walker scale(28). The
Baden-Walker scale is fast, simple, and has been
used widely in recent studies on cystocele repair,
with which we wished to compare our results(29).
Follow-up visits were performed at 2, 6 and 12
months after the last VEL procedure.
At each follow up the patients were interviewed
about post-op adverse effects and their level of
satisfaction. Patient satisfaction with the outcome
of treatment was measured on a 4-point scale:
not satisfied, partially satisfied, satisfied or very
satisfied. Pain during the treatment was measured
for every session with a 10-point VAS pain scale.
All the results are reported as the Mean ±
SD of absolute values. Statistical significance
(α=0.05) was calculated with Crosstabs and
the Chi-square test, as well as with one-way
ANOVA and Bonferroni tests in SPSS 17.0 (SPSS
Science, Chicago, IL, USA) and GraphPad Prism
(GraphPad, La Jolla, CA, USA).
RESULTS
In this study 61 patients suffering from pelvic
organ prolapse were included. Their average age
was 54.9 ± 9.1years (range: 29-78 years). Mean
parity was 2.2 ± 0.8: 42 patients had 2 children
(69%), 8 patients had 1 child (13%), 6 patients 3
children (10%), and 3 patients 4 children (5%).
Only 2 patients (3%) were nulliparous. The average
BMI was 25.5 ± 3.1 (range: 19-32). Distribution of
cystocele stages according to the Baden-Walker
(BW) scale at baseline is reported in Table 1.
Twenty patients (33%) had had a hysterectomy,
40 patients (66%) had a concurrent rectocele and 8
patients (13%) had a concurrent uterine prolapse.
No patient had had previous POP surgery. 7% of
the patients underwent two procedures, 60% three,
26% four and 7% underwent five procedures.
There was a significant improvement in
BW grade already after the first laser treatment
(p<0.001). At the time of first follow-up, 48% of the
patients improved to BW grades 0 or 1 (Table 1).
FU-1
(n=61;
2 months)
7 (12%)
22 (36%)
27 (44%)
5 (8%)
1.5
FU-2
(n=61;
6 months)
21 (35%)
28 (46%)
10 (16%)
2 (3%)
0.9
FU-3
(n=52;
12 months)
20 (39%)
24 (46%)
8 (15%)
0.8
Baseline
(n=61)
40 (66%)
15 (24%)
6 (10%)
2.4
BW Grade
0
I
II
III
IV
Average
grade
Table 1.
Distribution of cystocele stages according to the Baden-Walker scale
(BW Grade) at baseline and at three follow-ups
It. J. Gynaecol. Obstet.
2017, 29: N. 1
22
Non-ablative laser treatment of cystocele
The differences between average prolapse grades
at baseline and at each follow-up were highly
statistically significant (p<0.001, Fig. 1).
Additional laser treatments brought additional
improvement in BW grade. By the second follow-
up, 81% of patients had improved to a grade 0
or 1 cystocele (Table 1). At the third follow-up,
there were no longer any patients with a cystocele
stage above 2 (Table 1). 39% had normal organ
position (grade 0 cystocele) and a further 46% of
the patients were asymptomatic with a grade 1
cystocele (Table 1).
On average, cystoceles improved by 1.6 grades
(Fig. 2) and 95% of cystoceles improved by at
least one grade. After the final treatment 57% of
the patients were very satisfied with the outcome,
33% were satisfied and 8% were partially satisfied.
Only 1 patient was not satisfied with the outcome
(2%).
Treatment discomfort was very low; the
average pain level on a 10-point VAS scale was
0.49 during the first procedure, 0.22 during the
second and 0.17 during the third procedure. There
were no adverse effects reported.
Many of the patients had concurrent rectoceles
or uterine prolapses at baseline. These prolapses
also improved after the laser treatment of
cystoceles, but as the treatment of cystoceles
was the main objective of our study, these
improvements are not described here.
Baseline cystocele grade had a significant
(p=0.007) effect on the reduction in BW grade at
the final follow-up. The majority of patients with
grade 2 cystoceles at baseline improved to grade
0 (50%) or grade 1 (43%) after laser treatment, but
some 7% remained at grade 2. 20% of the patients
with grade 3 cystoceles at baseline improved
to grade 0 after treatment, 40% improved to
grade 1 and the remaining 40% to grade 2. Of
all the patients diagnosed with the severest POP
(grade 4), a full 83% improved to grade 1 and
the remaining 17% to grade 2. All the patients
diagnosed with either grade 3 or 4 cystoceles
therefore showed improvement after treatment.
There were no statistically significant
differences in improvement between patients
with or without a hysterectomy. For patients that
had undergone hysterectomy, the treatment was
a full success (grade 0 cystocele) in 40% of the
cases. The final diagnosis was grade 1 for 35% and
grade 2 for the remaining 25%. Patients without
a hysterectomy procedure were diagnosed at the
end of treatment with grade 1 cystocele in 51% of
the cases, grade 2 in 12%, while 37% were grade 0.
DISCUSSION
The results of this preliminary pilot study
suggest that the nonablative VEL is an effective
and safe tool for the treatment of cystoceles. In
most of the patients the improvement occurred
after the first treatment, with patients reporting
better prolapse containment inside of the vaginal
canal and less frequent occurrence of the prolapse
falling out of vaginal canal. Further treatments
induced additional improvement in up to 85% of
patients to grade 0 or 1 cystocele. In comparison,
3 years after POP surgery 93% of patients had
grade 0 or 1 cystocele(29). However, VEL has none
of the side effects of POP surgery (fever, urinary
retention, de novo urinary incontinence, mesh
extrusion, mesh retraction, dyspareunia, chronic
pelvic pain)(29).
*** -statistical significance, p<0.001
Figure 1.
Average cystocele stages before VEL treatment and at 3 follow-ups.
The bars show mean POP grade value ± SEM
Figure 2.
Cystocele grade reduction after VEL treatment from baseline to the last
follow-up. Bars present mean values. 13% improved by 3 grades, 44% by 2
grades and 38% by one grade. 5% did not improve.
The average improvement was 1.6 grades
Average POP grade
Baseline 6 months2 months 12 months
Change in POP stage
% of patients
23
Non-ablative laser treatment of cystocele Urska Bizjak Ogrinc et al.
A typical example of prolapse improvement
after laser therapy is shown in Fig. 3, while Fig. 4
presents the improvement of a large (grade 4)
prolapse in a 66-year-old patient.
There were no significant differences in
prolapse improvement with respect to the
patients’ ages or with respect to the number
of procedures applied. The decision about the
number of treatments was based on the level
of improvement observed after the second
procedure. The patients with lower rates of
improvement received additional treatments.
The largest group of patients (60%) received
three procedures; the second largest group (26%)
received four procedures.
Twenty patients included in this study
(33%) had previously undergone hysterectomy.
Although hysterectomy is recognized as a risk
factor for POP(30,31) previous hysterectomy did not
significantly affect the outcome of VEL treatment
Figure 3.
Pelvic organ prolapse in a 63 year old woman (a) before and (b) after 3 laser
treatments
Figure 4.
Reduction of grade 4 prolapse in a 66 year old woman with 4 vaginal
deliveries after the laser therapy: (a) before the therapy, (b) one month after
the first session, (c) one month after the second session, (d) one month
after the third session, (e) 3 months and (f) 6 months after the last (fourth)
session.treatments
in this study. The laser treatment was successful
(post-treatment BW grades 0 or 1) in 75% of post-
hysterectomy patients.
There is a well-established connection
between collagen deficiency and the occurrence
of POP. Lammers et al.(32) compared the
incidence of various collagen disorders between
POP patients and a control group and found a
significantly higher prevalence of other collagen-
related disorders, such as varicose veins, joint
hypermobility and rectal prolapse, in the POP
group. Han et al.(33) have observed abnormal
connective tissue architecture, decreased collagen
expression and increased frailness of the tissue
in patients with POP and SUI. Genetic collagen-
associated disorders have also been associated
with an increased incidence of POP(34).
In this pilot study, we report a novel approach
of treating cystocele using a VEL thermal-only
treatment. The idea comes from pilot studies
of a laser therapy designed for the treatment of
vaginal relaxation syndrome and stress urinary
incontinence that reported improvement of
POP as an additional effect(18). The treatment
uses innovative low-fluence pulse sequences
(SMOOTH™ mode) to achieve precise heating
of the tissue up to 65°C without causing ablation
or damage to the epithelium. Pulses of heat
in the range of 60-65°C have been shown to
achieve immediate shrinkage of collagen, while
maintaining its structure without destruction(16,17).
Besides the immediate shrinkage of collagen,
heat pulsing stimulates the synthesis of new
collagen, as the heat induces a heat-shock healing
response(17,27). Stacking of low-fluence pulse
sequences has been shown in numerical models(35),
as well as animal(36,37) and human studies(38), to be
effective in shrinking the collagen in the dermis
up to a depth of several hundred micrometers,
without causing damage to the epidermis.
The above-mentioned principle was applied
in several studies that aimed to treat different
conditions arising from pelvic floor dysfunction,
such as vaginal relaxation and stress urinary
incontinence (SUI)(18,23–26). Recently, Gambacciani
et al.(20,21) have reported a study using the non-
ablative VEL for the treatment of genitourinary
symptom of menopause, with a significant
decrease in symptoms of SUI in a subset of
incontinent women(20,21).
The overall success rate (post-treatment BW
grade 0 or 1) in our study was 85%. Surgical
methods can achieve higher cure rates, but are also
associated with higher costs and a higher rate of
side effects and re-operation(1,10,29).
It. J. Gynaecol. Obstet.
2017, 29: N. 1
24
Non-ablative laser treatment of cystocele
The most popular method for cystocele
treatment in the past decade has been surgical
insertion of polypropylene meshes(11,12,29). There has
been a lot of controversy regarding polypropylene
meshes following their reclassification by the FDA
into high-risk Class III medical devices due to
numerous side effects(39,40). These developments
have emphasized the lack of effective and safe
therapies for POP. We believe that the minimally
invasive VEL treatment could play an important
role in the future as an intermediate step between
currently available conservative therapies and
surgery. Many of the patients in this study enlisted
due to a fear of surgery or because they already had
undergone previous surgery (e.g. hysterectomy)
and were trying to avoid or postpone re-operation.
The large majority of the patients were satisfied
with the procedure and the results of the therapy.
The follow-up in this study showed that the
results of laser treatment could last at least 12
months. Long-term experiences with the same
Er:YAG modality in aesthetics and dermatology
suggest that the procedure could be safely repeated
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