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The diagnostic role of office hysteroscopy
and three-dimensional endometrial volume
measurement in evaluation of women with
peri menopausal bleeding
Thesis Submitted for Fulfillment of the M.D degree in
Obstetrics & Gynecology
BY
Ayman Hany Ahmed (M.B.B.Ch.,M.Sc)
Assistant lecturer -Faculty of Medicine-Cairo University
Supervised by:
Prof. Ayman Abd El Halim Marzouk Professor of obstetrics and gynecology
Faculty of Medicine-Cairo University
Dr.Hassan Mostafa Gaafar Lecturer of obstetrics and gynecology
Faculty of Medicine-Cairo University
Faculty of medicine
Cairo University
2012
بسم اهلل الرحمن الرحيم
وانحكمة انكتاب عهيك انهه وأوزل ..} فضم وكان تعهم تكه نم ما وعهمك
{ عظيما عهيك انهه 113اآلية - انىساءسورة
Acknowledgement
To the almighty, most gracious and most merciful ALLAH, to
him above all, humbly, I praise and express my utter and
wholehearted thanks.
To Prof. Dr.Ayman Abd El Halim Marzouk , I give tribute of
what words can convey of gratitude for his enthusiastic help,
fatherly guidance, care and encouragement.
To Dr. Hassan Mustafa Gaafar, I express my sincere
gratefulness, for his precious assistance and invaluable practical
guidance and remarks.
I want to express my appreciation to the department of
Obstetrics and Gynecology in Cairo University, and all my
colleagues working in the hospital for the efforts that helped me
to perform this work.
Finally I am expressing my thankfulness and gratitude for
my family that beard me and helped me a lot all through my
life.
List of Contents
List of abbreviations II
List of tables IV
List of figures V
Introduction 1
Aim of the work 4
Review of literature
Chapter 1 A- Endometrium 6
B- perimenopausal bleeding 21
Chapter 2
Endometrial Sampling & Pathology of Some
Uterine Lesions
40
Chapter 3 Hysteroscopy
58
Chapter 4 Ultrasonography 72
Patients and Methods 96
Results 101
Discussion 116
Summary 123
Conclusion 127
References 128
Arabic Summary 151
Abstract
Abnormal uterine bleeding (AUB) is overall the most common
causes of gynecological visits in the perimenopausal age, involving about
15% of women. Endometrial assessment has traditionally been achieved
by obtaining tissue for histological analysis utilizing blind in-patient
dilatation of the cervix and curettage of the endometrium under general
anesthesia Diagnosis and treatment of endometrial pathology can
nowadays benefit from well-established techniques, ranging from clinical
examination to transvaginal ultrasound (TVS), 3D ultrasonography and
hysteroscopy .
Patients and methods:This study included 100 patients complaining of
perimenopausal bleeding. All the selected patient had subjected to
carefull history taking and then underwent general examination, local
pelvic examination, office hysteroscopy transvaginal 2D pelvic
ultrasound, 3D endometrial volume measurement and then dilatation and
curettage (D&C) or hystroscopic guided biopsy for focal endometrial .
Those patients were divided into 2 groups based on the endometrial
histopathology into:
Group A patients with hyperplasia and malignant conditions.
Group B patients with other causes of abnormal uterine bleeding.
Results:The age ranged between 41 and 50 years with a mean of 49.4 ±
1.22 years. They had a mean parity of 3.2 The most common bleeding
pattern was menorrhagia In group 1 the most common endometrial
histopathology was simple endometrial hyperplasia. In group 2 most
common endometrial histopathology was disordered proliferative
endometrium. In our study there was a high statistical significance as
regard endometrial thickness in comparison of both groups; In group 1
endometrial thickness was 15.37 ± 2.27mm , while in group 2 it was
11.90 ± 2.97mm. As regards the measurement of endometrial volume, in
our study there was a high statistical significance in comparison of both
groups; in group 1 endometrial thickness was 14.11 ± 2.1cc, while in
group 2 it was 7.67 ± 1.81cc. Also endometrial volume was significantly
different when used to compare between atrophic endometrium and other
benign endometrial pathology. As regards the results of hysteroscopy, it
showed the highly statistical significance in the ability to differentiate
between group 1 and 2. In group 1 it was able to detect 82% of
hyperplasia cases and 100% of endometrial cancer cases while in group 2
it was able to detect 76% of cases.
Keywords:
Three Dimensional measurement of the endometrial volume, office
hysteroscopy, endometrial biopsy perimenopausal bleeding,
II
List of Abbreviations
ABBREVIATIONS DETAILS
2 D Two-Dimensional.
3D Three-Dimensional
17β-HSD 17 β - hydroxysteroid dehydrogenase
ACOG American College of Obstetricians and Gynecologists
AUB Abnormal Uterine Bleeding
BMI Body Mass Index
CBC Complete Blood Count
CEH Complex Endometrial Hyperplasia
CT Computerized Tomography
D&C Dilatation And Curettage
DHEAS Dehydroepiandrosterone Sulfate
DNA Deoxyribonucleic Acid
DPE Disordered proliferative Endometrium
EC Endometrial Carcinoma
EIC Endometrial Intraepithelial Carcinoma
EIN Endometrial Intraepithelial Neoplasia
EMB Endometrial Biopsy
EMP Endometrial Polyp
FIGO International Federation Of Gynecology And Obstetrics
FSH Follicle-Stimulating Hormone
GNRH Gonadotropin-Releasing Hormone
HCG Human Chorionic Gonadotropin
HNPCC Hereditary Non Polyposis Colorectal Cancer
IGFBPS Insulin-Like Growth Factor Binding Proteins
IGFS Insulin-Like Growth Factors
III
ISGP International Society Of Gynecological Pathologists
IUD Intrauterine Device
NPV Negative Predictive Value
NS Non Significant
PAI-1 Plasminogen Activator Inhibitor-1-
PCOS Polycystic Ovary Syndrome
PG Prostaglandin
PGE2 Prostaglandin E 2
PGF2α Prostaglandin F2 Alpha
PGS Prostaglandins
PID Pelvic Inflammatory Disease
POP Progestin-Only Pill
PPV Positive Predictive Value
PR Progesterone Receptor
RBCS Red Blood Cells
RCOG Royal College Of Obstetricians And Gynecologists
SEER Surveillance, Epidemiology and End Results
(source for cancer statistics in the United States)
SEH Simple Endometrial Hyperplasia
SEM Scanning Electron Microscopy
SHBG Sex Hormone-Binding Globulin
SIS Saline-Infusion Sonography
STRAW Stages Of Reproductive Aging Workshop
TAS Transabdominal Sonography
TNF-Α Tumor Necrosis Factor-Α
TVS Transvaginal Sonography.
VOCAL Virtual Organ Computer-Aided Analysis
WHO World Health Organisation
IV
List of tables
table No. Description Page
No. 1.
Differential diagnosis of Abnormal Uterine Bleeding. 27
2. Terms used to describe patterns of AUB 28
3. Additional Etiology of Menorrhagia 30
4. Differential diagnosis of postmenopausal bleeding 32
5. Age and Parity in both groups. 102
6. Bleeding pattern in both groups 104
7.
Number of different endometrial histopathology In
both groups . 105
8. Endometrial thickness in both groups 106
9. Endometrial thickness in Group1. 107
10. Endometrial thickness in Group2. 108
11. Endometrial volume in both groups 109
12. Endometrial volume in Group1 . 109
13. Endometrial volume in Group2 . 110
14. Office hysteroscopy results in both groups. 112
15. Office hysteroscopy results in correlation with
histopathological results in both groups. 112
V
List of figures
Figure
No. Description Page
No.
1.
Scanning Electron Micrograph of endometrial
epithelium (a) on day 17 and (b) day 20 a natural cycle 8
2. The Uterine Vasculature 10
3. Uterine cycle 11
4.
Relationship between different time periods surrounding the
menopause 24
5. Randall suction curette 39
6. Pipelle suction cannula 39
7. Pipelle suction cannula 39
8. Novak curette 44
9. Randall curette 44
10. Vabra aspirator 44
11. Tis-U-Trap 44
12. Microscopic picture of an EMP 47
13. Microscopic picture of adenomyomatous polyp 48
14. Microscopic picture of simple hyperplasia 50
15. Microscopic picture of complex hyperplasia. 51
16. Microscopic picture of leiomyoma 53
17. Microscopic picture of endometrioid adenocarcinoma 56
18. Microscopic picture of endometrial adenoacanthoma 56
19. Microscopic picture of uterine papillary serous carcinoma 56
20. Microscopic picture of senile atrophic endometrium 57
21. Normal panoramic view of the uterine cavity 66
22. Endometrial polyp 68
23. Cystic glandular hyperplasia 69
24. Focal polypoid endometrial hyperplasia. 70
25. Increased endometrial thickness in endometrial hyperplasia 70
26. Endometrial carcinoma 71
27. Ultrasound of endometrium during menstruation:
Shows a thin endometrial lining 77
VI
28. Ultrasound of late proliferative endometrium:
Shows the endometrium with a trilaminar appearance 77
29. Ultrasound of secretory endometrium:
Shows a thickened echogenic endometrium 77
30. Ultrasound of postmenopausal endometrium:
Shows a thin atrophic endometrium 77
31.
Ultrasound of endometrial polyp:
Shows a thickened endometrium with sonoluscent cystic
spaces
78
32.
Ultrasound of endometrial polyp:
Shows marked endometrial thickening associated with
subendometrial cysts resulting from tamoxifen therapy
78
33. Ultrasound of intramural fibroids 80
34. Ultrasound of submucous fibroid: 81
35. Ultrasound of subserous fibroid 81
36. Ultrasound of adenomyosis: 82
37. Ultrasound of adenomyosis: 82
38. Ultrasound of endometrial hyperplasia 83
39.
Ultrasound of endometrial hyperplasia:
(Above) Transverse US image of the uterus shows a markedly
thickened, heterogeneous endometrial echo complex .
(Below) Transverse image from saline hysterosonography of
the same patient, shows multiple endometrial polyps
84
40.
Ultrasound of endometrial carcinoma:
The endometrium is thickened and irregular.
85
41. Ultrasound of endometrial carcinoma:
TVUS shows marked irregular thickening of the endometrium 85
42.
Ultrasound of endometrial carcinoma:
Transverse ultrasound images showing:
(A) Gray-scale US demonstrate diffuse endometrial
thickening.
(B) Power Doppler US shows multiple vessels within the
86
43. Ultrasound of atrophic endometrium: 87
VII
The endometrial echo is seen as thin echogenic line
44.
Calculation using VOCALTM software of endometrial
volume (a) and power Doppler indices (vascularization index
(VI), flow index
(FI) and vascularization flow index (VFI)) in the
endometrium.
93
45. Mean Age in both groups 103
46. Mean Parity in both groups 104
47. Bleeding pattern in both groups 105
48. Number of different endometrial histopathology In
both groups . 106
49. Endometrial thickness in both groups 107
50. Endometrial thickness in Group1 . 107
51. Endometrial thickness in Group2 .
108
52. Endometrial volume in both groups 109
53. Endometrial volume in Group1 . 110
54. Endometrial volume in Group2 . 110
55. Samples of endometrial volume calculation by VOCAL. 111
56. Office hysteroscopy results in both groups.
112
57. hysteroscopy results in correlation with histopathological
results in group1 113
58. hysteroscopy results in correlation with histopathological
results in group2 113
59.
figure (59) Office hysteroscopy samples of both groups
DPE
secretory endometrium
Complex endometrial hyperplasia
Polypoid endometrium in SEH
114
Introduction
- 2 -
Introduction
Introduction
- 3 -
INTRODUCTION
Abnormal uterine bleeding (AUB) is overall the most common causes of
gynecological visits in the peri- and postmenopausal age, involving about
15% of women. Besides systemic, iatrogenic or hormonal age-related
causes, an endometrial pathology (polyps, sub- mucous myomas,
endometrial hyperplasia, and endometrial carcinoma) should always be
suspected, and evaluation appears to be mandatory (Nicholson W.K.etal.,
2001).Diagnosis and treatment of endometrial pathology can nowadays
benefit from well-established techniques, ranging from clinical
examination to transvaginal ultrasound (TVS), 3D ultrasonography and
hysteroscopy (Epstein E.,et.al.,2001).
The main advantage of hysteroscopy is to detect intracavitary lesions
such as leiomyomas and polyps that might be missed using transvaginal
sonography or endometrial sampling (Tahir et.al., 1999). In fact, some
have advocated hysteroscopy as the primary tool for the diagnosis of
abnormal uterine bleeding. Although it is highly accurate for identifying
endometrial cancer, it is less accurate for endometrial hyperplasia. Thus,
some recommend endometrial biopsy or endometrial curettage in
conjunction with hysteroscopy (Clark, 2002).
Gruboeck et al. reported that the assessment of endometrial volume
in women with postmenopausal bleeding was more accurate than
endometrial thickness measurement for detecting endometrial pathology
(Gruboeck et.al.,1996). Bonilla-Musoles and coworkers reported that 3D
US improved the diagnostic accuracy of ultrasound to determine
myometrial and cervical invasion in endometrial carcinoma (Bonilla M.F.
et.al.,1997 ).
Aim of the work
- - 4
Aim of the work
Aim of the work
- - 5
Aim of the work
This study was undertaken to determine the role of office hysteroscopy and
three-dimensional (3D) ultrasonographic measurement of the endometrial
volume and if those methods could predict malignant conditions and
hyperplasia of the endometrium and if they could exclude serious
intrauterine pathology in perimenopausal women with irregular uterine
bleeding to minimize further operative interventions especially for
surgically high risk patients.
Chapter 1
A-Endometrium
-6-
Chapter 1
Chapter 1
A-Endometrium
-7-
A- Endometrium
Chapter 1
A-Endometrium
-8-
Endometrium
Endometrial histology
Endometrium which is the inner mucous uterine layer is soft, spongy and
composed of tissue resembling embryonic connective tissue. The
endometrial epithelium is columnar and gland forming (tubular glands that
open into the cavity of the uterus) with a specialized spindle shape stromal
cells (Progenitors of decidual cells)(Anderson & Gendadry, 2007).
The endometrial epithelium consists of two types of cells that are easily
distinguishable by scanning electron microscopy (SEM): the secretory and
the ciliated cells (Fig. 1). The morphology of ciliated cells does not change
much during the cycle. In contrast, the secretory cells bear microvilli (MV)
and undergo hormone-dependent changes (Martel, et al, 1981; Nikas, et
al., 2000).
The concentration of these ciliated cells around gland openings and the
ciliary beat pattern influence the mobilization and distribution of
endometrial secretions during the secretory phase. Cell surface MV, also a
response to estradiol, are cytoplasmic extensions and serve to increase the
active surface of cells (Speroff & Fritz, 2005).
(a) (b)
Figure (1) Scanning Electron Micrograph of endometrial epithelium (a) on day
17 and (b) day 20 a natural cycle. (Martel, et al., 1981)
Chapter 1
A-Endometrium
-9-
The endometrium can be divided morphologically into
An upper two-thirds functionalis layer which is composed of:
Superficial compact zone (stratum compactum)
A deeply situated intermediate zone (stratum spongiosum).
The lower one-third basalis layer.
The purpose of the functionalis layer is to prepare for the implantation of
the blastocyst; therefore, it is the site of proliferation, secretion, and
degeneration. The purpose of the basalis layer is to provide the
regenerative endometrium following menstrual loss of the functionalis
(Flowers & Wilborn, 1984).
The Uterine Vasculature
The two uterine arteries that supply the uterus are branches of the internal
iliac arteries. At the lower part of the uterus, the uterine artery separates
into the vaginal artery and an ascending branch that divides into the
arcuate arteries (Fig 2).The arcuate arteries run parallel to the uterine
cavity and anastomoses with each other, forming a vascular ring around the
cavity. Small centrifugal branches (the radial arteries) leave the arcuate
vessels, perpendicular to the endometrial cavity, to supply the
myometrium. When these arteries enter the endometrium, small branches
(the basal arteries) extend laterally to supply the basalis layer. These basal
arteries do not demonstrate a response to hormonal changes. The radial
arteries continue in the direction of the endometrial surface, now assuming
a corkscrew appearance (and now called the spiral arteries), to supply the
functionalis layer of the endometrium. It is the spiral artery (an end artery)
segment that is very sensitive to hormonal changes (Speroff & Fritz,
2005).
One reason that the functionalis layer is more vulnerable to vascular
permutations is that there are no anastomoses among the spiral arteries.