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.