Endometriosis: A Comprehensive Update

122 Pages·2015·2.6 MB·English

by  Sajal Gupta

SPRINGER BRIEFS IN REPRODUCTIVE BIOLOGY
Sajal Gupta
Avi Harlev
Ashok Agarwal
Endometriosis
A Comprehensive
Update
123
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Sajal Gupta • Avi Harlev • Ashok Agarwal
Endometriosis
A Comprehensive Update
Sajal Gupta, MD Avi Harlev, MD
Assistant Professor, Lerner College of American Center for Reproductive
Medicine and Case Western Reserve Medicine
University Cleveland , OH , USA
American Center for Reproductive
Lecturer, Soroka University Medical Center
Medicine
Fertility and IVF Unit
Cleveland Clinic
Ben-Gurion University of the Negev
Cleveland , OH , USA
Beer-Sheva, Israel
Ashok Agarwal, PhD
Professor, Lerner College of Medicine and
Case Western Reserve University
American Center for Reproductive
Medicine
Cleveland Clinic
Cleveland , OH , USA
ISSN 2194-4253 ISSN 2194-4261 (electronic)
SpringerBriefs in Reproductive Biology
ISBN 978-3-319-18307-7 ISBN 978-3-319-18308-4 (eBook)
DOI 10.1007/978-3-319-18308-4
Library of Congress Control Number: 2015944099
Springer Cham Heidelberg New York Dordrecht London
© The Author(s) 2015
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Contents
1 Introduction to Endometriosis ............................................................... 1
Sajal Gupta, Avi Harlev, Ashok Agarwal, Elizabeth Pandithurai,
and Caroline Cirenza
1.1 Defi nition ......................................................................................... 1
1.2 Classifi cation of Endometriosis ....................................................... 1
1.2.1 ASRM Classifi cation (Stage 1 to Stage 4) ........................... 2
1.3 Disease Burden: Prevalence of Endometriosis Worldwide
and in North America ....................................................................... 2
1.4 Symptoms and Signs of Endometriosis ........................................... 3
1.5 Disease Background ......................................................................... 4
1.5.1 Historical Perspectives ......................................................... 4
1.6 Key Points and Summary ................................................................. 4
References ................................................................................................. 4
2 Predisposing and Protective Factors of Endometriosis ....................... 7
Sajal Gupta, Avi Harlev, Ashok Agarwal, and Elizabeth Pandithurai
2.1 Predisposing Factors ........................................................................ 7
2.1.1 Early Menarche, Late Menopause, Low Parity .................... 7
2.1.2 Hormonal Factors: High Estrogen and Low Progesterone ..... 7
2.1.3 Exposure to Environmental Agents Such as Dioxins .......... 8
2.1.4 Immunological Dysregulation ............................................. 9
2.1.5 Genetic Predisposition and Epigenetic Alterations.............. 10
2.1.6 Persistent Infl ammatory Status ............................................ 11
2.2 Protective Factors ............................................................................. 12
2.3 Key Points and Summary ................................................................. 12
References ................................................................................................. 13
v
vi Contents
3 Theories on Endometriosis ..................................................................... 17
Sajal Gupta, Avi Harlev, Ashok Agarwal, and Elizabeth Pandithurai
3.1 Sampson’s Theory ............................................................................ 17
3.2 Coelomic Metaplasia ....................................................................... 18
3.3 Embryonic Rest Theory ................................................................... 18
3.4 Lymphatic and Vascular Metastasis Theory .................................... 19
3.5 TIAR (Tissue Injury and Repair) Theory ........................................ 19
3.6 Quinn’s “Denervation-Reinnervation” Theory ................................ 19
3.7 Stem Cell Theory ............................................................................. 19
3.8 Key Points and Summary ................................................................. 20
References ................................................................................................. 20
4 Oxidative Stress and Endometriosis ...................................................... 23
Sajal Gupta, Avi Harlev, Ashok Agarwal, Alaa Al Safaar,
Akshay Gupta, and Garrett Hack
4.1 What Is Oxidative Stress? ................................................................ 23
4.2 Role of Macrophages, Interleukins in Causing
Oxidative Stress ............................................................................... 23
4.3 Mechanistic Pathway Connecting Oxidative Stress
and Endometriosis ............................................................................ 26
4.4 Nitric Oxide and Endometriosis ....................................................... 26
4.5 Is Oxidative Stress a Cause or Effect of Endometriosis? ................. 26
4.6 Measurement of Oxidative Stress Markers ...................................... 27
4.6.1 The Function of Thioredoxin (TRX)
and Thioredoxin- Binding Protein-2 (TBP-2) ...................... 28
4.7 Role of Antioxidants as a Defense System
Against Oxidative Stress .................................................................. 29
4.7.1 Vitamins E, A, C and Melatonin as Anti-Oxidants .............. 29
4.7.2 Studies on Antioxidant Rich Diet
in Endometriosis Patients..................................................... 31
4.8 Key Points and Summary ................................................................. 33
References ................................................................................................. 33
5 Role of Iron in the Pathogenesis of Endometriosis .............................. 37
Sajal Gupta, Avi Harlev, Ashok Agarwal, Sheila Gokul,
and Deepika Kumaresan
5.1 Iron: Background ............................................................................. 37
5.2 Iron Regulated Genes ....................................................................... 37
5.3 Retrograde Menstruation and Iron Levels in Endometriosis ........... 38
5.4 Iron and Oxidative Stress ................................................................. 42
5.4.1 Fenton Reaction ................................................................... 42
5.5 Mechanistic Pathway of Iron Induced Oxidative Stress
in Endometriosis .............................................................................. 42
5.6 Hemoglobin: Haptoglobin Complex, Hemopexin
and Fenton Reaction ........................................................................ 43
Contents vii
5.7 Ferritin, Transferrin, and Hemosiderin ............................................ 44
5.8 Long-Term Consequences of Iron Overload .................................... 45
5.9 Key Points and Summary ................................................................. 46
References ................................................................................................. 46
6 Role of Environmental Pollutants in Endometriosis ............................ 49
Sajal Gupta, Avi Harlev, Ashok Agarwal, Beena Premkumar,
Cansu Yazar, and Roshni Kakaiya
6.1 Introduction ...................................................................................... 49
6.2 Classifi cation of Environmental Pollutants ...................................... 50
6.3 Toxic Effects of Environmental Pollutants ...................................... 50
6.3.1 Human Studies ..................................................................... 50
6.3.2 Animal Studies ..................................................................... 50
6.4 Mechanism of Toxic Induction ........................................................ 50
6.5 AhR Modulation and Its Impact on Endometriosis
Development .................................................................................. 51
6.6 Activation of Growth Factors ......................................................... 51
6.7 Gene Dys-Regulation ..................................................................... 52
6.8 Immunosuppression ....................................................................... 53
6.9 Altered Hormone Signaling Pathways ........................................... 54
6.10 Prevention and Management .......................................................... 56
6.11 Key Points and Summary ............................................................... 57
References ................................................................................................. 58
7 Endometriosis and Ovarian Cancer ...................................................... 61
Sajal Gupta, Avi Harlev, Ashok Agarwal, Akshay Gupta,
Monica Gray, Kristina Solvik, and Maria DeLeonibus
7.1 Introduction .................................................................................... 61
7.2 Sampson’s Theory of Malignant Transformation .......................... 61
7.3 Ovarian Cancers Associated with Endometriosis .......................... 62
7.4 Genetic Alterations Common in Endometriosis and EAOC .......... 62
7.5 Mechanistic Pathways Underlying Conversion of Ovarian
Endometriosis to EAOC ................................................................. 63
7.5.1 PI3K/AKT-Pathway............................................................ 67
7.6 Preventive Measures and Screening Options ................................. 69
7.6.1 Screening ............................................................................ 71
7.7 Key Points and Summary ............................................................... 72
References ................................................................................................. 73
8 Endometriosis: Impact on Patient Quality of Life ............................... 75
Sajal Gupta, Avi Harlev, Ashok Agarwal, Nathan Reynolds,
Tahir Beydola, and Namariq Haroun
8.1 Introduction .................................................................................... 75
8.2 Measures of Quality of Sexual Life ............................................... 75
8.3 Pain Related Measures ................................................................... 76
8.4 Measures to Assess Depression ..................................................... 76
viii Contents
8.5 Measures to Assess Anxiety .......................................................... 76
8.6 Measures Related to Professional Life .......................................... 77
8.7 Key Points and Summary ............................................................... 77
References ................................................................................................. 77
9 Diagnosis of Endometriosis .................................................................... 79
Sajal Gupta, Avi Harlev, Ashok Agarwal, Julia Ellis-Kahana,
and Caroline Cirenza
9.1 Introduction .................................................................................... 79
9.2 Gold Standard: Invasive Diagnostic Technique ............................. 79
9.3 Existing Diagnostic Techniques ..................................................... 80
9.4 Need for Non-invasive Diagnostic Technique ............................... 80
9.5 Peripheral Biomarkers for Endometriosis ...................................... 81
9.5.1 Biomarkers: Peripheral Blood ............................................ 81
9.6 Potential Biomarker for Non-invasive Diagnosis .......................... 83
9.6.1 Biomarkers: Peritoneal Fluid (Pf) ...................................... 83
9.6.2 Biomarkers: Eutopic Endometrium .................................... 87
9.6.3 Biomarkers: Follicular Fluid (FF) ...................................... 89
9.6.4 Biomarkers: Ectopic Endometrium .................................... 90
9.7 Key Points and Summary ............................................................... 91
References ................................................................................................. 91
10 Management of Endometriosis .............................................................. 95
Sajal Gupta, Avi Harlev, Ashok Agarwal, Mitali Rakhit,
Julia Ellis-Kahana, and Sneha Parikh
10.1 Pharmacological Treatment ........................................................... 95
10.1.1 Hormonal Therapies ........................................................ 96
10.1.2 Analgesics ........................................................................ 98
10.1.3 Melatonin ......................................................................... 98
10.2 Surgical Treatment of Endometriosis............................................. 98
10.2.1 Ovarian Endometriomata Surgical Management ............. 98
10.2.2 Ovarian Endometriomata Aspiration ............................... 99
10.2.3 Deep Endometriosis Surgical Treatment ......................... 99
10.3 Treating Endometriosis to Improve ART Outcomes ..................... 99
10.3.1 Introduction ..................................................................... 99
10.3.2 Endometrioma Aspiration ............................................... 100
10.3.3 Endometrioma Ablation .................................................. 101
10.3.4 Ovarian Cystectomy ........................................................ 101
10.4 Recent Advances in Management of Endometriosis ..................... 103
10.4.1 Introduction ..................................................................... 103
10.4.2 Hormonal Agents ............................................................. 103
10.4.3 Non Hormonal Agents ..................................................... 104
10.4.4 Surgical Techniques Robotic Surgery ............................. 105
Contents ix
10.5 New Frontiers in Management of Endometriosis .......................... 106
10.5.1 Endometriosis Diagnosis ................................................. 106
10.5.2 Endometriosis Treatment ................................................. 106
10.6 Key Points and Summary ............................................................... 107
References ................................................................................................. 107
11 Concluding Remarks .............................................................................. 113
Sajal Gupta, Avi Harlev, Ashok Agarwal