.

Sergiu Gladun MD, PhD

USMF N.Testemitanu

Bibliography
Haynes PJ, et al. Measurement of menstrual blood loss in
patients complaining of menorrhagia. Br J Obstet Gynaecol
1977 Oct;84(10):763-8
Cote I, et al. Work loss associated with increased menstrual
loss in the United States. Obstet Gynecol 2002
Oct;100(4):683-7
Higham JM, et al. Assessment of menstrual blood loss using a
pictoral chart. Br J Obstet Gynaecol. 97: 734-9, 1990.
Hallburg I et al. Acta Obstet Gynecol Scand. 1966; 45:320-5
Saidi MA et al. J.Ultrasound Med. 16:587-591, 1997
Grimes DA. Am J. Obstet Gynecol. 142:1-6, 1982
Gimpelson et al. Am J. Obstet Gynecol. 158:489-492, 1988
Farquhar CM et al. Obstet Gynecol. 2002: 99:229-234
Carlson K. et al. Obstet Gynecol. 83:556, 1994
Drvyer N. et al. Br. J. Obstet Gynecol. 100:237, 1993

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Definition of DUB
The widely accepted definition of DUB
is abnormal bleeding, with no definable
organic cause (fibroids, polyps) in
patients in absence of pregnancy.

Differential Diagnosis DUB

Pregnancy Complications
Intra-Uterine Pathology
Fibroids, Polyps
Endometrial Cancer or Hyperplasia

Cervical Pathology
Cancer, Pre-Neoplastic Conditions

Adenomiosis

Diagnostic Techniques

History and Physical exam

(TVS)

Saline infusion sonography (SIS)
- (MRI)

Evaluation / Ultrasound
GYN endovaginal (EVS) ultrasound transvaginal sonography
(TVS) very helpful, measure endometrial lining (stripe), detects
fibroids, etc.
Sensitivity for endometrial abnormalities 41%, , specificity 98%,
positive predictive value 95% and negative predictive value 64%
Saline Infusion Sonography (SIS) or sonohysterography (SHG)
more accurate, higher specificity, 36% of normal TVS found to
have pathology on SIS.

Ko, et al, abstract JOGC, Oct. 2001)

Preferred over office hysteroscopy by patients.

Widrich, et al Am J Obstet Gynecol. 1996

Timmerman, et al Am J Obstet Gynecol. 1998)

May get more definitive diagnosis, ie. Global vs focal problems

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Diagnostic Hysteroscopy
By far the best and most
informative tool in assessing the
uterine cavity.
In office use of hysteroscopy is the
future

ISTORIC
* 1869 - Pentru prima dat Pantaleoni a efectuat
histeroscopia
* 1895 - la Congresul ginecologilor din Viena Bumm a
prezentat rezultatele examinrilor cavitii uterine cu
ajutorul uretroscopului.
* 1914 - Cu scop de nlturare a sngelui din cavitatea
uterului
Heineberg a folosit un sistem de splare.
* 1927 - Miculicz - Radecki i Freund au construit un
chiuretoscop histeroscop ce permitea biopsia sub
control vizual. Grans a creat un dispozitiv dotat cu
sistem de splare.
* mplementarea n practica medical a fibrelor optice i
a sistemelor optice de lentile.
*1976 Neuwirth a utilizat rezectoscopul pentru
nlturarea nodulului submucos - a nceput era

ACTUALITATEA TEMEI
* Actualmente histeroscopia - cea mai larg aplicat
metod pentru diagnosticarea patologiei intrauterine,
dar i pentru intervenii chirurgicale la nivelul cavitii
uterului.
* Depistarea patologiei intrauterine n timpul
histeroscopiilor la paciente cu rezultate normale ale
ecografiei atinge 20-40%.
* Conform datelor lui Makrakis E. et al., care a efectuat
examinri histeroscopice la paciente cu 2 tentative
nereuite de FIV n anamnez, la 36,6% a fost depistat
patologia intrauterin. La femeile crora li s-a efectuat
histeroscopia a fost determinat o frecven statistic
veridic mai nalt fa de pacientele crora nu li s-a

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Aparatajul necesar pentru

histeroscopie

Monitor, surs de
lumin, camer
video

Histeroscop operativ,
optic (unghi de vizualizare 0% si
30%),
foarfec, pens bioptic

Sistem de infuzie

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Rezultatele obinute

Polip endometrial
n cazul depistrii
Polip
polipilor endometriali
polipectomie cu
foarfec i/sau pens
bioptic. n cazul
polipilor cu baz lat
sau polipoz difuz,
s-a recurs la
chiuretajul cavitii
uterine, cu control
histeroscopic ulterior
Polip
a eficienei
procedurii..

Sinehii intrauterine
S-a efectuat adezioliza
folosind foarfeca i/sau
chiureta cu
introducerea ulterioar
de sterilet intrauterin
pentru perioada de 7
zile, antibioticoterapie
timp de 5-7 zile i
hormonoterapie pentru
2-3 luni n perioada
postoperatorie cu scop
de prevenire a
recidivului..

Clasificarea histeroscopic
sinehiilor intrauterine
Minime aderene fine cu obliterare
parial a cavitii
Grad mediu de exprimare
aderene miofibroase cu obliterare
parial a cavitii
Grad avansat de exprimare
aderene conjunctive cu obliterare
masiv.

Miom uterin
Pacientelor
depistate cu noduli
miomatoi
intramuralsubmucoi ce
deformeaz
cavitatea uterin
le-a fost propus
miomectomia
conservativ.

Nodul submucos

Nodul submucos

Nodul miomatos submucos

Adenomioz
Pacientelor
depistate cu
adenomioz
li s-a propus
ulterior
terapia
hormonal

Focar de ad

Medical Management
Currently first line of defense according
to ACOG guidelines

NSAIDs
Birth Control Pills
GnRH Agonists Therapy
Progestins

Medical management of DUB

cost

effectivness

E/P Pills

50%

Progestagens

20%

Danazol
++

100%(dose)

GnRH`
++

100%

NSAID
Antifibronilytic

30%
50%

side effects
+
++
+
++
+
+



17 500 3 3
, 500 2
2 , 250
2 2
5-10 5 25
6-8 , 16 25 ..
3
150 / 2

Medical Management
Multiple Large Scale RCTs conducted
Long-term follow-up suggest:

success rate of ~ 25%

low patient satisfaction rate
Significant Side Effects
Over 50% hysterectomy rate at 5 years

Contraindicated for some patients

Surgical Management
D&C is no longer considered a Standardof-Care in Management of DUB
Can be used for management of profuse
bleeding
Not a viable long-term solution

Endometrial Ablation
Hysterectomy

First Generation
Endometrial Ablation
Systems

Goal of Endometrial
Ablation
Reduce Excessive Bleeding to
Normal Levels
Improve Quality of Life
Serve as a Minimally Invasive
Alternative to Hysterectomy

Goal of Endometrial
Ablation
Destroy the Endometrium
Destroy the Underlying
Basal Layer and
Superficial Myometrium

Nd:YAG Laser
First Attempt to Ablate the
Endometrium using LASER Energy.
First described by Goldrath M (1981)

Requires Very Well Developed

Hand/Eye/Foot Coordination
Did not Find Wide Acceptance due to
Very High Level of Technical Skill
Required and Cost Associated with the
Procedure

Nd: YAG LASER

Performance

Images from the photo library of the WEL Foundation, UK

Hysteroscopic Ablation

Karl Storz
Olympus
ACMI
Wolf

Technology Overview
Considered Gold Standard
Hysteroscopic Skills Required
Continuous Flow Instrumentation
Utilizes a Mono-Polar RF Energy
Non-Conductive Distension Media
Required

Fluid Monitoring Required

Fluid Intravasation

Performed by 15% of Gyns in US

Global Ablation
Technologies Rationale
Inconsistent Results
Complications
Technical Complexity
Time Consuming
High Cost

Second Generation
(Global)
Endometrial Ablation
Technologies

Balloon-Type Technologies

Technology Overview
Ablation Device-Fluid Filled Thermal
Balloon
Circulating Hot Fluid
Operates by Direct Heat Transfer
Procedure Terminates at:
Pressure Excess or Pressure Loss

Treatment Time 8 minutes

Cervical dilation ~ 6 mm
Pre-Treatment Required (i.e. Lupron, D&C)

Advantages
Portability
Short Learning Curve
Ease of Use
Extensive Clinical Experience
Proven to be Safe

Disadvantages
Need for Endometrial Pre-Treatment
Lower Success and Amenorrhea than
Rollerball group in the FDA trial
Low Amenorrhea Rates
12% (FDA Data)

Prolonged Treatment Time

27.4 minutes (FDA Data)

Intra- and Post-Procedure Cramping

Cornuas May be Left Un-, Under-treated

Free Circulating
Hot Saline

Overview

Hysteroscopic Control
Free Circulating Saline at 90C
Pressure Limited to 55mm Hg
Automatic shut-off after 10cc is Lost
Cervical Dilation 8.5 mm
Treatment 10 min + Warm-Up & Cool-Down
Limited Clinical Field Experience

Advantages
Although not FDA approved for, it is
marketed by manufacturer for intra-uterine
pathology and anatomical malformations.
Direct Visualization
FDA Approved

Disadvantages
Double Dose of GnRH Pre-Treatment Required
Lower Success and Amenorrhea than Rollerball
group in the FDA trial
13% Rate of Inadvertent Endocervical Ablation
Need for Hysteroscopic Equipment
Shut-off Occurs After Hot Fluid is Lost
Prolonged Treatment & Procedure Time
Need for Tight Cervical Seal
Second and Third Degree Vaginal Burns Reported

Overview
Uses Super-Low Temperature to Destroy
Tissue
Requires Ultrasonography During the
Procedure
Cervical Dilation 6.5 mm
Treatment Time Varies Depending on Number
of Freezes and Uterine Cavity Size
Limited Clinical Field Experience

Advantages
Physician and Patient Comfort with
the Concept of Cryo-Therapy
Portability
FDA Approved

Disadvantages

Mandated Need for Ultrasound Control

Endometrial Pre-Treatment Required
No Clear Treatment Protocol Developed
Lower Success and Amenorrhea than
Rollerball group in the FDA trial
Low Amenorrhea Rates
FDA Trial - 22%

Low Success Rates

FDA Trial - 68%

Microwave Energy

Overview
Surgical Tool vs. Ablation Device
Treatment time dependent on cavity size
and operator skill

Cervical Dilation 9 mm
Automatic Shut-off if T>95C
Reusable Hand-Held Device
Continuous Temperature Control
Limited Clinical Field Experience
~ 20,000 Patients Treated Worldwide

Advantages

Energy Delivery/Treatment Time Vary

Based on Cavity Size

Disadvantages

Operator Dependent
D&C contraindicated
Pre-treatment of the endometrium required
Mandated Ultrasound Confirming Miometrial
Thickness
To be performed within 24-48 hours before procedure
Minimal Thickness 10-mm

No Perforation Detection

27 Bowel Injuries Reported to FDA before Introduction in USA

Europe, Canada, Australia (before 2004)

9 Bowel Burns Reported Since Introduction in USA (2005 Data)

Expensive Capital Equipment

Large Unwieldy Control Box
Limited Clinical Data

NovaSure System

Overview
Uses Bipolar RF Energy
Treatment Time ~ 90 seconds
Cervical Dilation 7.5 mm
Perforation Detection System
Customized Energy Delivery & Ablation
Depth
No Distension of the Uterine Cavity
Significant Clinical Field Experience
~400,000 Patients Treated Worldwide

Advantages

Requires NO Endometrial Pre-Treatment

High Amenorrhea Rate
Fastest Treatment Time (~90 seconds)
Fastest Procedure Time (~4 minutes)
The Only Proactive Perforation Detection System
Ease of Use, Short Learning Curve
Treatment Possible at Any Time During the
Cycle, Including Active Bleeding
Low Intra- and Post-Operative Pain
Significant Number of Published Papers

Bi-Polar System Safety Features

Device Position Feedback
Cavity Integrity Assessment System
Hysteroflator Technology
Threshold Signal = 50 mm Hg for 4 seconds

Self-Terminating Procedure based on

Tissue Impedance or Time
50 or 2 minutes

FDA Approved Endometrial

Ablation Systems

Global Endometrial
Ablation Technologies
Comparison of Clinical Results

Data Source
Summary of Safety and Effectiveness
Data from the Official FDA website:
ThermaChoice
http://www.fda.gov/cdrh/pdf/p970021.pdf
Her Option http://www.fda.gov/cdrh/pdf/p000032b.pdf
HTA http://www.fda.gov/cdrh/pdf/P000040b.pdf
NovaSure http://www.fda.gov/cdrh/pdf/P010013b.pdf
MEA http://www.fda.gov/cdrh/pdf2/p020031b.pdf

Requirement for
Endometrial Pre-Treatment

Ability to Accommodate for

Intracavitary Pathology

* Endometrial polyps of up to 2-cm

Treatment Time
(Time of Energy Delivery)

min

Procedure Time

(Device Insertion-Device Removal)

min

No data available for Freezing and Microwave

Applicability of
Local IV Sedation

Amenorrhea Rate at 12Months

Study Success Rate

(PBLAC 75)

Reduction to Normal
Bleeding
(PBLAC<100)

No Data For Freezing Technology & Microwave

Patient Satisfaction
(Patients with 12-Months Follow-Up)

No data available for Free Hot Saline

Intra- and Immediate PostOperative

Adverse Events
(First 24 hours)

Adverse Events at 2 Weeks

Follow-Up

Adverse Events Between

2-Weeks and 1-Year Follow-Up

Do they work?
Five year follow-up data suggests
that hysterectomy was avoided in:

70% of patients with ThermaChoice

83% of patients with MEA
97% of patients with NovaSure

Do they work?

Hysterectomy in USA
Chronic Pelvic
pain 10%
(Pr) cancer
10%

Myoma 30%
(180 000/year)

Prolaps 15%

Endomtriosis/Adnomyosis
20%

DUB 20%
(120 000/year)

Hysterectomy Types
Open

Total Hysterectomy
Sub-Total Hysterectomy
Vaginal Hysterectomy

Minimally Invasive
Laparoscopically Assisted Vaginal
Hysterectomy
Vaginal Hysterectomy

Hysterectomy
Benefits
Ultimate solution
High success and patient satisfaction

Detriments

Morbidity
Mortality
Loss of organ
Psychological Problems
Sexual Problems

Conclusions
DUB is a diagnosis of exclusion
Differential diagnosis is critical
Medical therapy has a low effectiveness
Endometrial ablation appears to be most
appropriate treatment solution
Hysterectomy is a solution, but cannot
be justified without first attempting the
use of a minimally invasive alternative

Thank You