Accepted Manuscript New Technologies and Innovations in Hysteroscopy Mary Connor
PII:
S1521-6934(15)00059-0
DOI:
10.1016/j.bpobgyn.2015.03.012
Reference:
YBEOG 1482
To appear in:
Best Practice & Research Clinical Obstetrics & Gynaecology
Received Date: 3 February 2015 Accepted Date: 18 March 2015
Please cite this article as: Connor M, New Technologies and Innovations in Hysteroscopy, Best Practice & Research Clinical Obstetrics & Gynaecology (2015), doi: 10.1016/j.bpobgyn.2015.03.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
RI PT
New Technologies and Innovations in Hysteroscopy
Mary Connor
EP
TE D
M AN U
SC
Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
AC C
Mary Connor, Department of Obstetrics and Gynaecology, Jessop Wing, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK S10 2SF. [email protected]
ACCEPTED MANUSCRIPT Abstract Ambulatory services, with the performance of diagnostic and operative hysteroscopy as an outpatient or office procedure, are providing much of the stimulus for the development of devices that will offer women a better hysteroscopy experience. For the many women who
RI PT
are readily able to tolerate outpatient hysteroscopy it offers significant advantages, as they can receive safe, efficient and effective assessment and treatment of abnormal uterine bleeding, with avoidance of the disadvantages of general anaesthesia and hospital admission. In
SC
addition, provision of such services is cost effective. Whilst the focus for the development of new devices has been the improvement of ambulatory hysteroscopy services, new
M AN U
instrumentation may be beneficial for hysteroscopy procedures in any setting. For ambulatory services important goals are to reduce pain and the duration of procedures, and to enable the ready delivery of both diagnostic and therapeutic outpatient hysteroscopy.
TE D
This article discusses innovations for both diagnosis and treatment. Much of the information available about these new devices has been obtained from the manufacturers or from published abstracts submitted for presentation at international meetings that have not been
EP
peer reviewed. Some of the reported studies have been randomised controlled trials, others
AC C
the results of early investigations.
Key Words: imaging systems, ambulatory hysteroscopy, hysteroscopy sheath, endometrial ablation devices, hysteroscopic morcellation.
2
ACCEPTED MANUSCRIPT A. New devices for hysteroscopy Imaging systems with readily portable cameras and light sources can be used in examination rooms that are not solely dedicated for hysteroscopy, and enable more flexible use of space
RI PT
and without the storage difficulties of bulky, conventional imaging stacks.
A.1. EndoSee™
The EndoSee™ device (CooperSurgical, Trumbull, CT, USA) is novel (figure 1). It is a
SC
handheld, battery-operated hysteroscopy system that consists of two main parts. The
‘HandTower™’ contains a small (3.5 inch diagonal) touch screen LCD display monitor, with
M AN U
video and control electronics and a rechargeable battery. It weighs 400 g; a charging cradle is provided. The hysteroscopes are single-use semi-rigid curved cannulas with a diameter of 15F (4.5 mm) and length of 287 mm. The lens, camera and light source are placed at the tip, and comprise a digital processing chip with a CMOS (complementary metal–oxide–
TE D
semiconductor) sensor, as used in mobile phone and web cameras, with integrated LED (light emitting diode) dual light sources. The CMOS sensor has low static power consumption. The LED light provides a high intensity light, but without significant heat production, which
EP
is important as it is placed inside the uterine cavity. There is a port at the proximal end of the
AC C
cannula to which can be attached a syringe or inflow tubing for saline irrigation.
Results of observational studies using the device for diagnostic hysteroscopy, primarily in an office setting, were presented as open communications in the new instrumentation section of the AAGL Congress, 2013 [1, 2, 3]. It was reported that good quality hysteroscopic images were obtained with the device and with minimal need for cervical dilatation. Munro et al
3
ACCEPTED MANUSCRIPT collected data for 24 women who underwent office diagnostic hysteroscopy with the device in one of nine medical centres in the USA [2]. Patient discomfort ranged from none to modest, insertion was generally easy, good visualisation was obtained and it was found to be easy to use. The findings of these investigators supports use of the device in a non-specialised
RI PT
examination room, as it has the potential to replace the more usual bulky monitor, camera and light source equipment and without the need for sterilisation facilities.
SC
Other cannulas for use with the HandTower™ may become available for endometrial biopsy and operative procedures, but these require further development [4]. The role of EndoSee™
M AN U
in the United Kingdom has yet to be determined.
A.2. UBIPack GYN
The purpose of the UBIPack GYN (SoproComeg, La Ciotat cedex, France) is to provide a
TE D
portable system for undertaking hysteroscopic procedures (figure 2). It consists of a 1CCD (charge-coupled device) camera that has a lower power consumption that the standard CCD camera, with three metres of cable which can be inserted into a USB port of a laptop or
EP
personal computer (not provided). It can be used with either flexible or rigid endoscopes and
AC C
the software, ICE (Intelligent Control Endoscope) technology provided enables the camera to recognise and adapt to the endoscope in use. Both regular and pendulum heads are available. Light is provided by a compact LED source (UBILIGHT) that has a long duration of use (50,000 hours) and with the equivalent light intensity of a 100W xenon source, but with lower heat emission. The computer software provided, Soproimaging, functions with Windows 7 and provides patient management screens and enables printing of medical reports. Conventional diagnostic and operative rigid hysteroscopes are available too; 30° rod lens, 2.7
4
ACCEPTED MANUSCRIPT mm diameter, 300 mm length hysteroscope with a 10 F (3.3 mm) diagnostic sheath and a 14.9 F (5.0 mm) operative sheath (continuous flow) with 5 F working channel.
RI PT
The CCD camera is typically used for medical and scientific applications and produces a higher quality image than the CMOS sensor previously described, but has higher power
SC
consumption.
M AN U
A.3. Tele Pack X LED
The Tele Pack X LED (Karl Storz, Tuttlingen, Germany) is not an entirely new system, but has been upgraded and now incorporates a new LED light source and 15 inch LED backlight monitor (figure 3). In addition, surgical procedures can now be recorded and downloaded via
TE D
USB ports or an SD card slot. It remains a portable, all-in-one system comprising light source and monitor and can be used with all Karl Storz one-chip camera heads and video endoscopes and with a variety of other endoscopes. It is suitable for use in an office setting or
EP
operating theatre. The LED light source has an average service life of 30,000 hours and is
AC C
more powerful than the halide light source of the previous model, but with lower heat generation.
A4. Endo-shaft® disposable hysteroscopy sheath As an adjunct to the hysteroscopes that are available, an Italian company have developed a disposable sheath, Endo-shaft® (Xmed srl, Medolla, Italy) that provides a barrier between the
5
ACCEPTED MANUSCRIPT patient and the endoscope so that it can be used with another patient without being resterilised (figure 4). A single hysteroscope could be used for all patients. This may reduce preparation time, enabling more patients to be seen on a list and without the same capital expenditure. Irrigation fluid passes down the outer sheath and the view at the hysteroscope tip is through a
RI PT
clear window at the distal tip of the sheath. The sheath is reported by the company as having smooth rounded surfaces to allow it to easily pass through the cervical canal. Endoshaft can
SC
be used with the commonly available hysteroscopes.
B. New endometrial ablation devices
M AN U
As with other hysteroscopic developments, innovations in endometrial ablation devices for the treatment of heavy menstrual bleeding primarily focus on their use in an ambulatory
TE D
setting. The aim is to improve the experience of patients undergoing endometrial ablation when awake, whilst still providing adequate destruction of the endometrium. Besides being safe and effective, the procedures need to be of short duration, with associated minimal
EP
uterine pain and the avoidance of excessive cervical dilatation. A variety of ingenious
AC C
methods for endometrial destruction have recently been developed.
B.1. Minitouch
The Minitouch (MicroCube, Fremont, CA, USA) endometrial ablation device uses microwave energy, delivered from a small intrauterine device, to destroy the endometrium and treat HMB.
6
ACCEPTED MANUSCRIPT The device consists of a narrow (3.6 mm), flexible cannula covering the active element (figure 5a). After establishing the uterine cavity size, the cannula is inserted through the cervical canal to the uterine fundus; as it is so narrow cervical dilatation is unlikely to be necessary. The outer cannula is then withdrawn exposing the active element that self-deploys
RI PT
in the uterine cavity (figure 5b). After ensuring that the active element is firmly placed at the fundus, the cervical guard is advanced and the treatment cycle commences with safety checks before the microwave energy is delivered. Uterine cavities of 4 to 5 cm (internal cervical os
SC
to fundus) require a single instalment of 60 seconds; longer cavities receive a second shorter (30 seconds) exposure of microwave energy after the device has been withdrawn by two
M AN U
centimetres. Once the treatment is completed the device is removed from the cavity, it is recommended that hysteroscopic examination of the cavity be postponed for at least a minute to allow the delivered energy to be fully effective.
TE D
A study examining the tissue effect of Minitouch on 20 freshly excised uteri was presented as
EP
an open communication at the AAGL Congress in 2011 [5]. It was reported that an ablation
AC C
depth of at least 5 mm at the mid-uterus level could be achieved, though with less depth at the cornua and lower cavity, and with serosal surface temperature measurements of 37.9 ± 3.2°C. Mean intracavitary temperatures were measured and were less than 70°C. Uniform endometrial ablation was observed histologically after appropriate tissue staining.
Clinical studies presented at the AAGL Congress in 2013 reported that the procedure is acceptable to women in outpatient settings without resource to anaesthesia [6]. Twenty women with HMB received 400 mg ibuprofen one hour pre-procedure, all treatments were
7
ACCEPTED MANUSCRIPT completed successfully; none required cervical dilatation. Pains scores, as measured on a 10 cm visual analogue scale (VAS), were reported with a mean of 4.8 (range 0 to 10). At a subsequent AAGL Congress in 2014, the outcomes for 37 women, one to 28 months following treatment, were presented during an open communication: 31 (84%) women
RI PT
reported amenorrhoea, 2 (5%) hypomenorrhoea, but 4 women (11%) had undergone hysterectomy [7].
SC
A recent development is that the active element can be removed and replaced from the
introductory cannula. The cannula can accommodate a small 2.9 mm diameter diagnostic
M AN U
hysteroscope and so can be introduced into the uterine cavity under direct vision; after cavity measurements have been made the hysteroscope is withdrawn and the active element introduced. This should provide greater confidence that a false passage has not been created
TE D
and that the device is safely placed in the uterine cavity.
Minitouch is in the midst of the FDA approval process and so is not available in the USA; the
AC C
other countries.
EP
device may be used in all EU countries, including Belgium, the United Kingdom, amongst
B.2. Minerva Endometrial Ablation System The Minerva Endometrial Ablation System (MinervaSurgical, Redwood City, CA. USA) uses heat generated by ionized argon gas particles colliding with a silicone balloon membrane to thermally destroy the adjacent endometrium (figure 6a).
8
ACCEPTED MANUSCRIPT The Minerva device is a bi-polar radio frequency (RF) system that uses electrical current to ionize argon gas that is fully contained within a sealed silicone balloon covering a cavitycompliant expandable frame (figure 6b). When the system is activated with a maximum of 40 watts, the argon gas circulating at low-pressure (25 mmHg) within the membrane is ionized
RI PT
into plasma. The ionized particles collide with the silicone membrane releasing energy and producing heat. The thermal energy is conducted into the adjacent tissue and fluids present within the uterine cavity, with transfer of heat to the endometrial tissue that is not in direct
SC
contact with the membrane. This ensures effective treatment of cavities of varying shapes due to asymmetry or small intrauterine pathology. The combination of direct membrane-to-
M AN U
tissue heat transfer, the ablative effect of heated liquids, and a small amount of bi-polar RF current travelling through the endometrial tissue (and resultant resistive heat), enables uniform, reproducible, and complete ablation of the uterine cavity.
TE D
The control unit generates the RF energy and monitors and manages its delivery to the patient. The power provided varies according to changes in impedance of the endometrial tissue during the ablation process, as well as dimensions of the uterine cavity. Although the
AC C
minutes.
EP
total energy delivered varies from patient to patient, the total ablation time is always two
The device when the balloon is closed has a diameter of 6mm; the silicone membrane is slippery and so should pass smoothly through the cervical canal. Following dilatation of the cervical os, if necessary, the silicone balloon is inserted into the uterine cavity and the array is opened. After deploying the device, a uterine integrity test (UIT) is performed using a flow of carbon dioxide gas into the cavity; a defect in the uterine cavity of 0.3 mm is said to be detectable. Leakage from the cervix during the UIT is prevented by inflation of a small
9
ACCEPTED MANUSCRIPT balloon that sits within the cervical canal. After successful completion of the UIT, the ablation cycle is automatically initiated and plasma energy is delivered. Upon completion of the two-minute ablation cycle, the array is closed, the cervical balloon deflated, and the device removed from the uterine cavity. The silicone surface should prevent adherence of
RI PT
ablated tissue.
All of the hand-piece is disposable. Attachments are placed at the back of the control unit for
SC
the argon and carbon dioxide gas canisters, which are supplied along with a power cord and
M AN U
footswitch.
Validation of the device for endometrial ablation is near completion and FDA approval is expected during the early part of 2015. The results of a single-arm, international, multi-centre study were given in an open presentation at the AAGL Congress, 2014 [8]. Of the 110 pre-
TE D
menopausal women with menorrhagia admitted to the study, 104 were successfully treated, one procedure was unsuccessful and five women failed screening. The primary objective was to evaluate the safety and effectiveness of the device in achieving a reduction to normal
EP
menstrual blood loss, a score of ≤75 as measured by the score on a pictorial blood assessment
AC C
chart (PBAC) at 12 months post-treatment, and to assess the occurrence of adverse events. Secondary objectives included the rate of amenorrhea. At twelve months follow-up 96.2% of women had a PBAC score of < 75 and 69.5% reported amenorrhoea. No patients had required hysterectomy or additional treatment for HMB. The result at twelve months was above the upper limit required by the FDA as determined by comparison with the success rates of other FDA approved ablation devices using the full data-sets given in each FDA study, where the calculated mean success rate is 75.6% (95%CI 65.6% to 83.5%) [9].
10
ACCEPTED MANUSCRIPT A prospective randomized- controlled trial has recently compared the Minerva system with rollerball endometrial ablation in 153 patients. The results are awaited, but preliminary results indicate that the device is shown to be as effective as in the single-arm study [9]. It is
RI PT
expected that both studies will be submitted soon for publication in peer-reviewed journals.
B3. Cerene™ Cryoablation Device
Channel MedSystems (San Francisco, USA) have developed Cerene™, a global endometrial
SC
ablation device that uses cryotherapy to induce destruction of endometrium for the treatment
M AN U
of heavy menstrual bleeding (figure 7). The device consists of a probe with an outer diameter of 5.8 mm and a self-contained, hand-held control system; it is single-use. After dilating the cervix, if necessary, the probe is inserted through the cervix to the uterine fundus and the outer sheath withdrawn, exposing the uterine liner. It is advised that the position of the device inside the uterine cavity is confirmed by ultrasonograpy. Once confirmed, the thin-
TE D
walled liner is filled with filtered-air to enable the liner to conform to the surfaces of the uterine cavity. Nitrous oxide gas, contained in a cylinder within the device handle, is released
EP
into the liner producing a cryogenic effect that is continued for 150 seconds; the gas is then removed by creating a vacuum and the probe is withdrawn. The device software is designed
AC C
to regulate the intrauterine pressure and an algorithm is incorporated into the software to detect uterine perforation.
Histopathological studies on nine women prior to hysterectomy confirmed an appropriate depth of ablation with shallower tissue damage at the cornua and lower uterine segment than the uterine body; the entire cavity surface was treated in all cases. The minimum and
11
ACCEPTED MANUSCRIPT maximum endomyometrial ablation depths were 4.9 ± 0.4 mm and 7.6 ± 0.6 mm respectively, and the closest distance between the cryoablated myometrium and serosal surface was 7.7 ± 2.4 mm, with a minimum of 5.2 mm [10]. No cryothermic injury to the endocervical canal
RI PT
was observed and there was no inadvertent damage of the myometrium or serosal surface.
The software algorithm for detecting uterine perforation was checked by deliberately forming a defect in the serosal surface of a number of uteri after hysterectomy and passing the device
M AN U
placement was detected and the device shutdown [11].
SC
through the hole before attempting to proceed to the cryoablation mode. The extrauterine
As the safety profile of the device appeared satisfactory, and it produced a suitable ablation profile with a single cryothermic episode and within an acceptable time, in vivo studies were subsequently undertaken. The ablation device was used on a small group of ten women who
TE D
then proceeded with a planned hysterectomy. It was reported as “well tolerated” without general anaesthetic or conscious sedation, though no pain scores are reported for the few
EP
women involved in the study [12].
AC C
Further studies are planned to assess its tolerability as an office procedure and outcome at six months following treatment for heavy menstrual bleeding.
B4. Librata
The Librata endometrial ablation system (LiNA Medical, Glostrup, Denmark) is a thermal balloon device than functions independently of a generator as it is battery driven. The whole device is disposable, including the handheld control unit that contains the device software; the battery is attached once the packaging is opened (figure 8).
12
ACCEPTED MANUSCRIPT
Prior to treatment glycerine is heated in insulated chambers inside the hand piece; this takes fix to six minutes. After determining the cavity length (cervix to fundus) the catheter is
RI PT
inserted into the uterine cavity and the silicone balloon inflated with the heated solution. The Librata catheter is 5 mm in diameter, so narrower than many of the other endometrial ablation devices. The software measures the pressure inside the balloon and adjusts the amount of
SC
fluid to maintain a pressure of 175 mmHg (160-187 mmHg). Throughout the two-minute treatment-cycle the fluid is retracted into one of two heating chambers, then returned to the
M AN U
balloon a total of four times. This ensures that the temperature of 150°C (±5°C) is maintained and that all areas of the endometrium are treated.
Safety features are built into the device. The balloon is tested to withstand refilling with
TE D
heated glycerine, the cervical cannula is insulated and there are mechanisms to prevent spillage of hot fluid in the unlikely event of balloon rupture. The handle has a bypass valve to allow emptying of the balloon in case of power loss, a cut-off switch prevents over heating of
EP
the fluid and accurate sensors monitor temperature and pressure. The device automatically
AC C
cuts off if there is a drop in pressure to below 92 mmHg and the system will not start if a pressure of 160 mmHg cannot be obtained. End of procedure notification on the LED display only flashes once extraction of glycerine from the balloon has been confirmed. The device is for single use and can only be activated once.
At this stage in the development of the device there is no published material on clinical outcomes of procedures. However, initial studies are being conducted in the United Kingdom and have proved successful [13]. It is planned for other centres to become involved and a Patient Register to be developed to collect data.
13
ACCEPTED MANUSCRIPT
B5. AEGEA endometrial ablation device The AEGEA Vapor System™ (Aegea Medical, Redwood City, CA, USA) device produces endometrial ablation by another new mechanism. Low-pressure hot water vapour is delivered
RI PT
into the uterine cavity through a 6 mm probe with consequent damage of the endometrium. Various uterine shapes can be accommodated because the vapour is released directly into the
SC
cavity. Treatment is of short duration, lasting only 120 seconds.
Clinical results were reported by Thurkow at the most recent AAGL meeting in 2014 [14].
M AN U
Twenty-two premenopausal women with HMB received endometrial ablation with the device. The main outcome reported for all 22 women was the reduction in menstrual blood loss to less than 80mL, as measured using the alkaline haematin method. The percentage of women achieving this target at three, six and twelve months were 75%, 85% and 95% respectively.
TE D
Other outcomes reported were the reduction in measured blood to less than 50% of the pretreatment level, this was achieved in 90%, 90% and 100% at 3, 6 and 12 months after treatment. Quality of life was also assessed at these times and all patients were reported to
AC C
were reported.
EP
have improved after treatment. No adverse events relating to the device or ablation procedure
The device is only currently available for use in the United States for clinical investigation; clinical studies with a view to obtaining FDA approval are underway.
B.6. NovaSure – next generation The NovaSure endometrial ablation system (Hologic, Inc., Marlborough, MA, USA) is not a new system as it was first introduced in 2001. However, a modified version of the NovaSure
14
ACCEPTED MANUSCRIPT device with a reduced in diameter of 6mm has recently become available (December 2014) and also an upgraded control unit (RFC10) (figure 9). The reduced diameter is as a result of refashioning of the bipolar electrode array so it fits into a narrower diameter delivery cannula. There is said to be no reduction in effectiveness and delivery of the radiofrequency energy,
RI PT
however, this has yet to be confirmed in large-scale studies. The new-generation NovaSure device also includes three previously introduced features, which are available on the current device: the rounded-off tip allows smoother passage through the cervical canal, the thumb-tab
SC
enables the cervical collar to fit more snugly even with a patulous cervical os, with reduced failure of the cavity integrity test due to leakage from the cervix. The control unit has a touch
M AN U
screen interface for recording the uterine cavity parameters and displays progress of the treatment procedure with a timer tracking the duration of the ablation. Studies confirming that the new-generation NovaSure is as effective as the older version are required.
TE D
C. Intrauterine morcellation
EP
Intrauterine morcellation devices, with mechanical removal of pathology under direct vision
AC C
and using normal saline for distension, are no longer so new, but there have been developments in the technology that warrant reporting. Smaller devices are now available and from the results of a trial comparing electroresection with hysteroscopic morcellation it seems that the latter is particularly suitable for endometrial polypectomy in an outpatient setting in both pre and postmenopausal women [15]. Polyp removal with the morcellator was quicker, less painful and more likely to be complete than with electrical resection (table 1.) Complications in the study were confined to self-limiting vasovagal reactions and one episode of endometritis that resolved with oral antibiotics.
15
ACCEPTED MANUSCRIPT
Other pathologies that can be removed with hysteroscopic morcellators include submucosal
RI PT
fibroids and placental remnants, as well as adhesions and uterine septa [16, 17, 18]. Small lesions (
PII:
S1521-6934(15)00059-0
DOI:
10.1016/j.bpobgyn.2015.03.012
Reference:
YBEOG 1482
To appear in:
Best Practice & Research Clinical Obstetrics & Gynaecology
Received Date: 3 February 2015 Accepted Date: 18 March 2015
Please cite this article as: Connor M, New Technologies and Innovations in Hysteroscopy, Best Practice & Research Clinical Obstetrics & Gynaecology (2015), doi: 10.1016/j.bpobgyn.2015.03.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
RI PT
New Technologies and Innovations in Hysteroscopy
Mary Connor
EP
TE D
M AN U
SC
Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
AC C
Mary Connor, Department of Obstetrics and Gynaecology, Jessop Wing, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK S10 2SF. [email protected]
ACCEPTED MANUSCRIPT Abstract Ambulatory services, with the performance of diagnostic and operative hysteroscopy as an outpatient or office procedure, are providing much of the stimulus for the development of devices that will offer women a better hysteroscopy experience. For the many women who
RI PT
are readily able to tolerate outpatient hysteroscopy it offers significant advantages, as they can receive safe, efficient and effective assessment and treatment of abnormal uterine bleeding, with avoidance of the disadvantages of general anaesthesia and hospital admission. In
SC
addition, provision of such services is cost effective. Whilst the focus for the development of new devices has been the improvement of ambulatory hysteroscopy services, new
M AN U
instrumentation may be beneficial for hysteroscopy procedures in any setting. For ambulatory services important goals are to reduce pain and the duration of procedures, and to enable the ready delivery of both diagnostic and therapeutic outpatient hysteroscopy.
TE D
This article discusses innovations for both diagnosis and treatment. Much of the information available about these new devices has been obtained from the manufacturers or from published abstracts submitted for presentation at international meetings that have not been
EP
peer reviewed. Some of the reported studies have been randomised controlled trials, others
AC C
the results of early investigations.
Key Words: imaging systems, ambulatory hysteroscopy, hysteroscopy sheath, endometrial ablation devices, hysteroscopic morcellation.
2
ACCEPTED MANUSCRIPT A. New devices for hysteroscopy Imaging systems with readily portable cameras and light sources can be used in examination rooms that are not solely dedicated for hysteroscopy, and enable more flexible use of space
RI PT
and without the storage difficulties of bulky, conventional imaging stacks.
A.1. EndoSee™
The EndoSee™ device (CooperSurgical, Trumbull, CT, USA) is novel (figure 1). It is a
SC
handheld, battery-operated hysteroscopy system that consists of two main parts. The
‘HandTower™’ contains a small (3.5 inch diagonal) touch screen LCD display monitor, with
M AN U
video and control electronics and a rechargeable battery. It weighs 400 g; a charging cradle is provided. The hysteroscopes are single-use semi-rigid curved cannulas with a diameter of 15F (4.5 mm) and length of 287 mm. The lens, camera and light source are placed at the tip, and comprise a digital processing chip with a CMOS (complementary metal–oxide–
TE D
semiconductor) sensor, as used in mobile phone and web cameras, with integrated LED (light emitting diode) dual light sources. The CMOS sensor has low static power consumption. The LED light provides a high intensity light, but without significant heat production, which
EP
is important as it is placed inside the uterine cavity. There is a port at the proximal end of the
AC C
cannula to which can be attached a syringe or inflow tubing for saline irrigation.
Results of observational studies using the device for diagnostic hysteroscopy, primarily in an office setting, were presented as open communications in the new instrumentation section of the AAGL Congress, 2013 [1, 2, 3]. It was reported that good quality hysteroscopic images were obtained with the device and with minimal need for cervical dilatation. Munro et al
3
ACCEPTED MANUSCRIPT collected data for 24 women who underwent office diagnostic hysteroscopy with the device in one of nine medical centres in the USA [2]. Patient discomfort ranged from none to modest, insertion was generally easy, good visualisation was obtained and it was found to be easy to use. The findings of these investigators supports use of the device in a non-specialised
RI PT
examination room, as it has the potential to replace the more usual bulky monitor, camera and light source equipment and without the need for sterilisation facilities.
SC
Other cannulas for use with the HandTower™ may become available for endometrial biopsy and operative procedures, but these require further development [4]. The role of EndoSee™
M AN U
in the United Kingdom has yet to be determined.
A.2. UBIPack GYN
The purpose of the UBIPack GYN (SoproComeg, La Ciotat cedex, France) is to provide a
TE D
portable system for undertaking hysteroscopic procedures (figure 2). It consists of a 1CCD (charge-coupled device) camera that has a lower power consumption that the standard CCD camera, with three metres of cable which can be inserted into a USB port of a laptop or
EP
personal computer (not provided). It can be used with either flexible or rigid endoscopes and
AC C
the software, ICE (Intelligent Control Endoscope) technology provided enables the camera to recognise and adapt to the endoscope in use. Both regular and pendulum heads are available. Light is provided by a compact LED source (UBILIGHT) that has a long duration of use (50,000 hours) and with the equivalent light intensity of a 100W xenon source, but with lower heat emission. The computer software provided, Soproimaging, functions with Windows 7 and provides patient management screens and enables printing of medical reports. Conventional diagnostic and operative rigid hysteroscopes are available too; 30° rod lens, 2.7
4
ACCEPTED MANUSCRIPT mm diameter, 300 mm length hysteroscope with a 10 F (3.3 mm) diagnostic sheath and a 14.9 F (5.0 mm) operative sheath (continuous flow) with 5 F working channel.
RI PT
The CCD camera is typically used for medical and scientific applications and produces a higher quality image than the CMOS sensor previously described, but has higher power
SC
consumption.
M AN U
A.3. Tele Pack X LED
The Tele Pack X LED (Karl Storz, Tuttlingen, Germany) is not an entirely new system, but has been upgraded and now incorporates a new LED light source and 15 inch LED backlight monitor (figure 3). In addition, surgical procedures can now be recorded and downloaded via
TE D
USB ports or an SD card slot. It remains a portable, all-in-one system comprising light source and monitor and can be used with all Karl Storz one-chip camera heads and video endoscopes and with a variety of other endoscopes. It is suitable for use in an office setting or
EP
operating theatre. The LED light source has an average service life of 30,000 hours and is
AC C
more powerful than the halide light source of the previous model, but with lower heat generation.
A4. Endo-shaft® disposable hysteroscopy sheath As an adjunct to the hysteroscopes that are available, an Italian company have developed a disposable sheath, Endo-shaft® (Xmed srl, Medolla, Italy) that provides a barrier between the
5
ACCEPTED MANUSCRIPT patient and the endoscope so that it can be used with another patient without being resterilised (figure 4). A single hysteroscope could be used for all patients. This may reduce preparation time, enabling more patients to be seen on a list and without the same capital expenditure. Irrigation fluid passes down the outer sheath and the view at the hysteroscope tip is through a
RI PT
clear window at the distal tip of the sheath. The sheath is reported by the company as having smooth rounded surfaces to allow it to easily pass through the cervical canal. Endoshaft can
SC
be used with the commonly available hysteroscopes.
B. New endometrial ablation devices
M AN U
As with other hysteroscopic developments, innovations in endometrial ablation devices for the treatment of heavy menstrual bleeding primarily focus on their use in an ambulatory
TE D
setting. The aim is to improve the experience of patients undergoing endometrial ablation when awake, whilst still providing adequate destruction of the endometrium. Besides being safe and effective, the procedures need to be of short duration, with associated minimal
EP
uterine pain and the avoidance of excessive cervical dilatation. A variety of ingenious
AC C
methods for endometrial destruction have recently been developed.
B.1. Minitouch
The Minitouch (MicroCube, Fremont, CA, USA) endometrial ablation device uses microwave energy, delivered from a small intrauterine device, to destroy the endometrium and treat HMB.
6
ACCEPTED MANUSCRIPT The device consists of a narrow (3.6 mm), flexible cannula covering the active element (figure 5a). After establishing the uterine cavity size, the cannula is inserted through the cervical canal to the uterine fundus; as it is so narrow cervical dilatation is unlikely to be necessary. The outer cannula is then withdrawn exposing the active element that self-deploys
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in the uterine cavity (figure 5b). After ensuring that the active element is firmly placed at the fundus, the cervical guard is advanced and the treatment cycle commences with safety checks before the microwave energy is delivered. Uterine cavities of 4 to 5 cm (internal cervical os
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to fundus) require a single instalment of 60 seconds; longer cavities receive a second shorter (30 seconds) exposure of microwave energy after the device has been withdrawn by two
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centimetres. Once the treatment is completed the device is removed from the cavity, it is recommended that hysteroscopic examination of the cavity be postponed for at least a minute to allow the delivered energy to be fully effective.
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A study examining the tissue effect of Minitouch on 20 freshly excised uteri was presented as
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an open communication at the AAGL Congress in 2011 [5]. It was reported that an ablation
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depth of at least 5 mm at the mid-uterus level could be achieved, though with less depth at the cornua and lower cavity, and with serosal surface temperature measurements of 37.9 ± 3.2°C. Mean intracavitary temperatures were measured and were less than 70°C. Uniform endometrial ablation was observed histologically after appropriate tissue staining.
Clinical studies presented at the AAGL Congress in 2013 reported that the procedure is acceptable to women in outpatient settings without resource to anaesthesia [6]. Twenty women with HMB received 400 mg ibuprofen one hour pre-procedure, all treatments were
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ACCEPTED MANUSCRIPT completed successfully; none required cervical dilatation. Pains scores, as measured on a 10 cm visual analogue scale (VAS), were reported with a mean of 4.8 (range 0 to 10). At a subsequent AAGL Congress in 2014, the outcomes for 37 women, one to 28 months following treatment, were presented during an open communication: 31 (84%) women
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reported amenorrhoea, 2 (5%) hypomenorrhoea, but 4 women (11%) had undergone hysterectomy [7].
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A recent development is that the active element can be removed and replaced from the
introductory cannula. The cannula can accommodate a small 2.9 mm diameter diagnostic
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hysteroscope and so can be introduced into the uterine cavity under direct vision; after cavity measurements have been made the hysteroscope is withdrawn and the active element introduced. This should provide greater confidence that a false passage has not been created
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and that the device is safely placed in the uterine cavity.
Minitouch is in the midst of the FDA approval process and so is not available in the USA; the
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other countries.
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device may be used in all EU countries, including Belgium, the United Kingdom, amongst
B.2. Minerva Endometrial Ablation System The Minerva Endometrial Ablation System (MinervaSurgical, Redwood City, CA. USA) uses heat generated by ionized argon gas particles colliding with a silicone balloon membrane to thermally destroy the adjacent endometrium (figure 6a).
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ACCEPTED MANUSCRIPT The Minerva device is a bi-polar radio frequency (RF) system that uses electrical current to ionize argon gas that is fully contained within a sealed silicone balloon covering a cavitycompliant expandable frame (figure 6b). When the system is activated with a maximum of 40 watts, the argon gas circulating at low-pressure (25 mmHg) within the membrane is ionized
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into plasma. The ionized particles collide with the silicone membrane releasing energy and producing heat. The thermal energy is conducted into the adjacent tissue and fluids present within the uterine cavity, with transfer of heat to the endometrial tissue that is not in direct
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contact with the membrane. This ensures effective treatment of cavities of varying shapes due to asymmetry or small intrauterine pathology. The combination of direct membrane-to-
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tissue heat transfer, the ablative effect of heated liquids, and a small amount of bi-polar RF current travelling through the endometrial tissue (and resultant resistive heat), enables uniform, reproducible, and complete ablation of the uterine cavity.
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The control unit generates the RF energy and monitors and manages its delivery to the patient. The power provided varies according to changes in impedance of the endometrial tissue during the ablation process, as well as dimensions of the uterine cavity. Although the
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minutes.
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total energy delivered varies from patient to patient, the total ablation time is always two
The device when the balloon is closed has a diameter of 6mm; the silicone membrane is slippery and so should pass smoothly through the cervical canal. Following dilatation of the cervical os, if necessary, the silicone balloon is inserted into the uterine cavity and the array is opened. After deploying the device, a uterine integrity test (UIT) is performed using a flow of carbon dioxide gas into the cavity; a defect in the uterine cavity of 0.3 mm is said to be detectable. Leakage from the cervix during the UIT is prevented by inflation of a small
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ACCEPTED MANUSCRIPT balloon that sits within the cervical canal. After successful completion of the UIT, the ablation cycle is automatically initiated and plasma energy is delivered. Upon completion of the two-minute ablation cycle, the array is closed, the cervical balloon deflated, and the device removed from the uterine cavity. The silicone surface should prevent adherence of
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ablated tissue.
All of the hand-piece is disposable. Attachments are placed at the back of the control unit for
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the argon and carbon dioxide gas canisters, which are supplied along with a power cord and
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footswitch.
Validation of the device for endometrial ablation is near completion and FDA approval is expected during the early part of 2015. The results of a single-arm, international, multi-centre study were given in an open presentation at the AAGL Congress, 2014 [8]. Of the 110 pre-
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menopausal women with menorrhagia admitted to the study, 104 were successfully treated, one procedure was unsuccessful and five women failed screening. The primary objective was to evaluate the safety and effectiveness of the device in achieving a reduction to normal
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menstrual blood loss, a score of ≤75 as measured by the score on a pictorial blood assessment
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chart (PBAC) at 12 months post-treatment, and to assess the occurrence of adverse events. Secondary objectives included the rate of amenorrhea. At twelve months follow-up 96.2% of women had a PBAC score of < 75 and 69.5% reported amenorrhoea. No patients had required hysterectomy or additional treatment for HMB. The result at twelve months was above the upper limit required by the FDA as determined by comparison with the success rates of other FDA approved ablation devices using the full data-sets given in each FDA study, where the calculated mean success rate is 75.6% (95%CI 65.6% to 83.5%) [9].
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ACCEPTED MANUSCRIPT A prospective randomized- controlled trial has recently compared the Minerva system with rollerball endometrial ablation in 153 patients. The results are awaited, but preliminary results indicate that the device is shown to be as effective as in the single-arm study [9]. It is
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expected that both studies will be submitted soon for publication in peer-reviewed journals.
B3. Cerene™ Cryoablation Device
Channel MedSystems (San Francisco, USA) have developed Cerene™, a global endometrial
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ablation device that uses cryotherapy to induce destruction of endometrium for the treatment
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of heavy menstrual bleeding (figure 7). The device consists of a probe with an outer diameter of 5.8 mm and a self-contained, hand-held control system; it is single-use. After dilating the cervix, if necessary, the probe is inserted through the cervix to the uterine fundus and the outer sheath withdrawn, exposing the uterine liner. It is advised that the position of the device inside the uterine cavity is confirmed by ultrasonograpy. Once confirmed, the thin-
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walled liner is filled with filtered-air to enable the liner to conform to the surfaces of the uterine cavity. Nitrous oxide gas, contained in a cylinder within the device handle, is released
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into the liner producing a cryogenic effect that is continued for 150 seconds; the gas is then removed by creating a vacuum and the probe is withdrawn. The device software is designed
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to regulate the intrauterine pressure and an algorithm is incorporated into the software to detect uterine perforation.
Histopathological studies on nine women prior to hysterectomy confirmed an appropriate depth of ablation with shallower tissue damage at the cornua and lower uterine segment than the uterine body; the entire cavity surface was treated in all cases. The minimum and
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ACCEPTED MANUSCRIPT maximum endomyometrial ablation depths were 4.9 ± 0.4 mm and 7.6 ± 0.6 mm respectively, and the closest distance between the cryoablated myometrium and serosal surface was 7.7 ± 2.4 mm, with a minimum of 5.2 mm [10]. No cryothermic injury to the endocervical canal
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was observed and there was no inadvertent damage of the myometrium or serosal surface.
The software algorithm for detecting uterine perforation was checked by deliberately forming a defect in the serosal surface of a number of uteri after hysterectomy and passing the device
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placement was detected and the device shutdown [11].
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through the hole before attempting to proceed to the cryoablation mode. The extrauterine
As the safety profile of the device appeared satisfactory, and it produced a suitable ablation profile with a single cryothermic episode and within an acceptable time, in vivo studies were subsequently undertaken. The ablation device was used on a small group of ten women who
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then proceeded with a planned hysterectomy. It was reported as “well tolerated” without general anaesthetic or conscious sedation, though no pain scores are reported for the few
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women involved in the study [12].
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Further studies are planned to assess its tolerability as an office procedure and outcome at six months following treatment for heavy menstrual bleeding.
B4. Librata
The Librata endometrial ablation system (LiNA Medical, Glostrup, Denmark) is a thermal balloon device than functions independently of a generator as it is battery driven. The whole device is disposable, including the handheld control unit that contains the device software; the battery is attached once the packaging is opened (figure 8).
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Prior to treatment glycerine is heated in insulated chambers inside the hand piece; this takes fix to six minutes. After determining the cavity length (cervix to fundus) the catheter is
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inserted into the uterine cavity and the silicone balloon inflated with the heated solution. The Librata catheter is 5 mm in diameter, so narrower than many of the other endometrial ablation devices. The software measures the pressure inside the balloon and adjusts the amount of
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fluid to maintain a pressure of 175 mmHg (160-187 mmHg). Throughout the two-minute treatment-cycle the fluid is retracted into one of two heating chambers, then returned to the
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balloon a total of four times. This ensures that the temperature of 150°C (±5°C) is maintained and that all areas of the endometrium are treated.
Safety features are built into the device. The balloon is tested to withstand refilling with
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heated glycerine, the cervical cannula is insulated and there are mechanisms to prevent spillage of hot fluid in the unlikely event of balloon rupture. The handle has a bypass valve to allow emptying of the balloon in case of power loss, a cut-off switch prevents over heating of
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the fluid and accurate sensors monitor temperature and pressure. The device automatically
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cuts off if there is a drop in pressure to below 92 mmHg and the system will not start if a pressure of 160 mmHg cannot be obtained. End of procedure notification on the LED display only flashes once extraction of glycerine from the balloon has been confirmed. The device is for single use and can only be activated once.
At this stage in the development of the device there is no published material on clinical outcomes of procedures. However, initial studies are being conducted in the United Kingdom and have proved successful [13]. It is planned for other centres to become involved and a Patient Register to be developed to collect data.
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B5. AEGEA endometrial ablation device The AEGEA Vapor System™ (Aegea Medical, Redwood City, CA, USA) device produces endometrial ablation by another new mechanism. Low-pressure hot water vapour is delivered
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into the uterine cavity through a 6 mm probe with consequent damage of the endometrium. Various uterine shapes can be accommodated because the vapour is released directly into the
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cavity. Treatment is of short duration, lasting only 120 seconds.
Clinical results were reported by Thurkow at the most recent AAGL meeting in 2014 [14].
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Twenty-two premenopausal women with HMB received endometrial ablation with the device. The main outcome reported for all 22 women was the reduction in menstrual blood loss to less than 80mL, as measured using the alkaline haematin method. The percentage of women achieving this target at three, six and twelve months were 75%, 85% and 95% respectively.
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Other outcomes reported were the reduction in measured blood to less than 50% of the pretreatment level, this was achieved in 90%, 90% and 100% at 3, 6 and 12 months after treatment. Quality of life was also assessed at these times and all patients were reported to
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were reported.
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have improved after treatment. No adverse events relating to the device or ablation procedure
The device is only currently available for use in the United States for clinical investigation; clinical studies with a view to obtaining FDA approval are underway.
B.6. NovaSure – next generation The NovaSure endometrial ablation system (Hologic, Inc., Marlborough, MA, USA) is not a new system as it was first introduced in 2001. However, a modified version of the NovaSure
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ACCEPTED MANUSCRIPT device with a reduced in diameter of 6mm has recently become available (December 2014) and also an upgraded control unit (RFC10) (figure 9). The reduced diameter is as a result of refashioning of the bipolar electrode array so it fits into a narrower diameter delivery cannula. There is said to be no reduction in effectiveness and delivery of the radiofrequency energy,
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however, this has yet to be confirmed in large-scale studies. The new-generation NovaSure device also includes three previously introduced features, which are available on the current device: the rounded-off tip allows smoother passage through the cervical canal, the thumb-tab
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enables the cervical collar to fit more snugly even with a patulous cervical os, with reduced failure of the cavity integrity test due to leakage from the cervix. The control unit has a touch
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screen interface for recording the uterine cavity parameters and displays progress of the treatment procedure with a timer tracking the duration of the ablation. Studies confirming that the new-generation NovaSure is as effective as the older version are required.
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C. Intrauterine morcellation
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Intrauterine morcellation devices, with mechanical removal of pathology under direct vision
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and using normal saline for distension, are no longer so new, but there have been developments in the technology that warrant reporting. Smaller devices are now available and from the results of a trial comparing electroresection with hysteroscopic morcellation it seems that the latter is particularly suitable for endometrial polypectomy in an outpatient setting in both pre and postmenopausal women [15]. Polyp removal with the morcellator was quicker, less painful and more likely to be complete than with electrical resection (table 1.) Complications in the study were confined to self-limiting vasovagal reactions and one episode of endometritis that resolved with oral antibiotics.
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Other pathologies that can be removed with hysteroscopic morcellators include submucosal
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fibroids and placental remnants, as well as adhesions and uterine septa [16, 17, 18]. Small lesions (
