Endometriosis and Adenomyosis Global Perspectives Across the Lifespan Engin Oral Editor 123 Endometriosis and Adenomyosis Engin Oral Editor Endometriosis and Adenomyosis Global Perspectives Across the Lifespan Editor Engin Oral Department of Obstetrics and Gynecology Bezmialem Vakif University Medical Faculty Istanbul, Turkey ISBN 978-3-030-97235-6 ISBN 978-3-030-97236-3 (eBook) https://doi.org/10.1007/978-3-030-97236-3 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022, corrected publication 2022 This work is subject to copyright All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Foreword Every person in the world is likely to have their life touched in some way by endometriosis or adenomyosis, so wide ranging is the suffering of almost 200 million souls on our globe who currently endure the ravages of these diseases, for some, every single day of their lives This wonderful book, Endometriosis & Adenomyosis: Across the Lifespan – Global Aspects, is in every regard global It is a global revelation of all that we know about endometriosis and adenomyosis – and much that we are yet to fully comprehend – and a global journey of an endometriosis/adenomyosis sufferer’s lifespan This book is written by an author group that represents the giants of our globe in this field, and is skilfully crafted and weaved together by gifted editor Engin Oral for us to enjoy and to learn Like you, I cannot wait to dive in Neil Johnson Professor of Reproductive Health, Robinson Research Institute Adelaide, SA, Australia Gynaecologist and REI Subspecialist, Auckland Gynaecology Group and Repromed, Auckland, New Zealand NZ Representative and Executive Board Member, ASPIRE Auckland, New Zealand Past President, World Endometriosis Society Vancouver, Canada The original version of this chapter was revised to reflect a correction to Dr Hanan Alsalem’s name which was misspelled in the initial publication as Hanan Amsalem An erratum to this chapter can be found at https://doi.org/10.1007/978-3-030-97236-3_45 v Foreword Endometriosis as a disease has many faces That might explain why it is called a chameleon And once suspected or diagnosed, it is hard to estimate the extent of the disease; thus, it has been compared with an iceberg as a major part of the tumor is hiding under the surface Endometriosis is benign but infiltrating; even though infiltration rarely turns malignant, it is hormone dependent yet cannot be cured by hormones Hypotheses of its origin are multifold, and treatment options are very limited Unfortunately, the interval from onset of symptoms to diagnosis of endometriosis on average takes years which is by far too long and effectively means suffering of predominantly young women in the prime years of their lives In association with underdiagnosing and under treatment are negative impacts on performance at work, school and university, sexual life, family relationship, and social activities Once diagnosed, the dilemma continues as medical treatment of endometriosis often interferes with family planning for couples because most hormonal therapies exert contraceptive effects, often requiring assisted reproductive technologies This is particularly true as in most developed countries couples desiring a child are beyond their thirties, which adds another fertility-reducing factor to endometriosis Following an often-unsuccessful medical treatment of endometriosis surgery remains the only choice for reducing pain and invasion into other organs However, since the difficulty of surgery exponentially increases with the extent of the disease, severe stages of endometriosis and adenomyosis require experts not only for diagnosis but also for treatment The editor of this textbook, Prof Engin Oral, has dedicated part of his life to increase awareness, understanding, and cognizance of medical specialists as well as the public about problems related to endometriosis He has successfully motivated a group of renowned experts in the field of endometriosis and adenomyosis to compile this up-to-date manual The careful reader will find a comprehensive collection of chapters which in total cover the entire field and allows for a holistic view on endometriosis and adenomyosis vii viii Foreword This book provides valuable information for anyone interested in in-depth knowledge regarding all aspects associated with endometriosis, offering practical application for daily practice Hans-Rudolf Tinneberg, MD, PhD Frauenklinik Nordwest Krankenhaus Frankfurt, Germany Foreword Endometriosis is among the most common gynecologic disorders associated with infertility and pelvic pain; therefore, it represents a major personal and public health concern Pathogenesis of endometriosis and adenomyosis has puzzled researchers for more than a century and still remains one of the most enigmatic disorders in gynecology In the last decade alone more than 5000 articles on endometriosis and adenomyosis appeared in the world scientific literature, many of them contradictory, reflecting our difficulties in deciphering this disorder More recently, the application of cellular and molecular biology techniques to the study of endometriosis allowed us to better understand the pathogenesis and pathophysiology of endometriosis and helped us to develop new therapeutic approaches Major advances in the understanding of endometrial biology and simultaneous advances in surgical instrumentation are critical elements fueling the endometriosis/adenomyosis renaissance This book, edited by Professor Engin Oral, is designed to present both cellular and molecular aspects and clinical management of endometriosis and adenomyosis It represents the culmination of the clinical experiences, basic research, and consensus opinions of experts in the field of endometriosis and adenomyosis A diverse group of internationally recognized experts have come together to provide a detailed discussion of various aspects of endometriosis and adenomyosis I would like to express my gratitude to Professor Oral for asking me to write a foreword to this book Our interaction began in 1994 as a mentor, but he became eventually a very valuable colleague and a friend As one of the international experts in endometriosis and adenomyosis, he has been a leader in the field, bringing awareness of these diseases to the public in general I hope that this book will serve women, their physicians, and investigators well in the ongoing battle against this enigmatic disease Aydin Arici, MD Professor of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine New Haven, CT, USA ix Preface Hello to all readers, I think I was introduced to endometriosis, also known as “chocolate cyst” disease, while I was studying medicine at Istanbul Medical Faculty At that time the name sounded a bit strange to me Later, when I chose obstetrics and gynecology, we came across endometriosis patients at Istanbul University Cerrahpaşa Medical Faculty, but now when I look at it, little did we know about the disease itself Patients were coming, saying “I have pain” or “I can’t get pregnant,” and sometimes we gave medical treatment, but mostly we performed surgery The person who made me realize this disease is my dear mentor from the USA, one of the foreword writers of this book, Prof Dr Aydin Arici When I was accepted as a postdoctoral fellow to Yale University Obstetrics and Gynecology Department of Reproductive Endocrinology and Infertility in 1995, I realized that Prof Arici was dealing mainly with endometriosis patients Thus, I joined his team and became acquainted with this disease I never knew about the research aspect of the disease, but during my time at Yale, as a team, my friends and I, under the leadership of Aydın Arici and now deceased David Olive, conducted both research and clinical studies that had contributed to the literature The first study we did was a clinical study, we looked at the effect of endometriosis on implantation, and when that study was accepted in the F&S journal, the head of the department at that time (Frederick Naftolin) and Aydın Arıcı sent me to the “Endometriosis 2000” meeting in May 1995, where important scientists were found I attended this meeting with Aydın Arıcı At that time, I had the opportunity to meet important people dealing with this issue in the USA, and this motivated me even more For the next 2 years, I dealt almost exclusively with this disease both in the laboratory and clinics I watched surgeries at Yale, had the opportunity to watch in vitro fertilization cases, and in the laboratory, we worked on molecules such as growth factors, cytokines in endometriosis tissue samples, and cell cultures When I returned to Turkey, my goal was to “provide better solutions to people suffering from this disease.” During this period, after becoming associate professor and professor, I had the chance to see many clinical cases at Istanbul University Cerrahpaşa Medical Faculty The years progressed rapidly, and in 2009, I decided to establish an association that provides academic education on this disease as well as increases the awareness of it among the public In retrospect, this was truly one of the best things I’ve ever done The association, which we established with 14 people, has now become a recognized and respected association not xi xii Preface only in Turkey but also throughout Europe and even worldwide This is the 12th year of the association, and if they were asked in these 12 years “What did you work for the most? What did you spend most of your time on? My answer will probably be the Endometriosis and Adenomyosis Society With this association, we primarily aimed to increase the knowledge and training of doctors on this subject In the following years, we tried to increase the public’s knowledge and awareness of the disease In 2012, we held the second meeting of the “Asian Endometriosis and Adenomyosis Association” in Istanbul The first took place in China and the second in Turkey under my presidency Just 2 years later, in 2014, under my chairmanship, we held a meeting on deep endometriosis in Istanbul, where international experts gave lectures on both theoretical and surgical cases In 2016, it was time to open our doors to Europe, and we were invited to Budapest for the meeting of the European Endometriosis Society, with the invitation of Dr Tinneberg and Dr Renner, founders of the “European Endometriosis Society.” There, Dr Taner Usta, who I’ve been always proud of as mentor and who is the current president of the Endometriosis and Adenomyosis Society, Turkey, and has been with me since almost the foundation of the association, and I were elected to the board of directors In 2018, I became the elected president of the European Endometriosis Society, and during this period, we organized the annual meetings of the European Endometriosis Society in Vienna and Prague In 2019, I was selected as a senior ambassador of the World Endometriosis Association In 2020, we faced COVID facts and we still have been struggling to live under pandemic As for the Endometriosis and Adenomyosis Association, we have mostly shifted our meetings online Since the last 2 years, we have been having only online meetings, webinars, etc As for the story of this book (what you have read so far is the story of me and the association), the idea of this book was seeded when my dear friend Prof Dr Orhan Bukulmez introduced me to Kristoffer Springer from Springer Nature during ASRM 2019 meeting After that meeting, Springer Nature officially invited me to edit an endometriosis book, and I gladly accepted this offer Our aim in this book was to create a bedside classic that covers the basics of endometriosis and adenomyosis When you see the chapters and topics, I think you will agree with me This book is the result of the joint effort of 87 authors from 19 diffferent countries who contributed in teams to create the 44 chapters of this book This book has been written by several experts on endometriosis from all over the world, but especially from Europe, who are the founders and/or members of the European Endometriosis Society I thank them all one by one At the beginning of this book, I would like to thank dear Orhan Bukulmez (USA), who helped to determine the topics, and dear Ertan Saridogan (England), one of the most hardworking and reliable people I know, with whom I always work with pleasure During the writing and editing phase, two of my students, who also have chapters in this book, contributed more than me My heartfelt thanks to my dear Nura Fitnat Topbas Selcuki (she has now started her PhD at Oxford University, Department of Women’s and Reproductive Health) and dear Ezgi Darici (she will start the ESHRE Travelling Fellowship Universitair Ziekenhuis Brussels – Reproductive Endocrinology 44 Recent Guidelines on Endometriosis and Adenomyosis 599 pregnancy Turkish guidelines also cover the impact of adenomyosis on fertility and emphasize there is some evidence that adenomyosis may compromise fertility and have a detrimental impact on the outcome of IVF treatment Limited evidence on the potential benefit of uterus-sparing surgery for adenomyosis in women who wish to preserve uterus/fertility has been summarized in the Turkish guidelines 44.8 Conclusion A number of national and international guidelines have been available since the publication of the first ESHRE Guidelines on the Management of Women with Endometriosis in 2005 [2] These have gradually evolved, and revised or updated versions have been published (ESHRE, CNGOF Guidelines) There are significant differences between the scope and focus of these guidelines; whilst some cover all aspects of endometriosis, others solely address endometriosis-associated infertility The majority of recommendations are in agreement with each other, although there are subtle differences between different guidelines References Vermeulen N, Le Clef N, Mcheik S, D’Angelo A, Tilleman K, Veleva Z, Nelen W. Manual for ESHRE guideline development, 2019 https://www.eshre.eu/ /Guidelines/Guidelines/ Manual-guidelines.pdf Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E, ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group ESHRE guideline for the diagnosis and treatment of endometriosis Hum Reprod 2005;20(10):2698–704 https://doi.org/10.1093/humrep/dei135 Epub 2005 Jun 24 PMID: 15980014 RCOG Green-Top Guidelines Endometriosis, Investigation and Management, 2007, Endometriosis, Investigation and Management (Green-top Guideline No 24) (rcog.org.uk) Practice bulletin no 114: management of endometriosis Obstet Gynecol 2010;116(1):223–236 doi: https://doi.org/10.1097/AOG.0b013e3181e8b073 PMID: 20567196 Leyland N, Casper R, Laberge P, Singh SS, SOGC. Endometriosis: diagnosis and management J Obstet Gynaecol Can 2010;32(7 Suppl 2):S1–32 PMID: 21545757 Koch J, Rowan K, Rombauts L, Yazdani A, Chapman M, Johnson N. Endometriosis and infertility – a consensus statement from ACCEPT (Australasian CREI consensus expert panel on trial evidence) Aust N Z J Obstet Gynaecol 2012;52(6):513–22 https://doi.org/10.1111/ j.1479-828X.2012.01480.x Epub 2012 Sep 27 PMID: 23016798 ASRM2012: Practice Committee of the American Society for Reproductive Medicine Endometriosis and infertility: a committee opinion Fertil Steril 2012;98(3):591–8 https:// doi.org/10.1016/j.fertnstert.2012.05.031 Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W, European Society of Human Reproduction and Embryology ESHRE guideline: management of women with endometriosis Hum Reprod 2014;29(3):400–12 https://doi.org/10.1093/humrep/ det457 Epub 2014 Jan 15 PMID: 24435778 College National des Gynecologues et Obstetriciens Francais Management of endometriosis CNGOF/HAS clinical practice guidelines, 2018 http://www.cngof.fr/pratiques-cliniques/ 600 E Sarıdoğan and N F Topbas Selcuki guidelines/apercu?path=RPC_CNGOF-HAS_Endometriose_Recommandations_2017-VA pdf&i=20535 10 Johnson NP, Hummelshoj L, World Endometriosis Society Montpellier Consortium Consensus on current management of endometriosis Hum Reprod 2013;28(6):1552–68 https://doi org/10.1093/humrep/det050 Epub 2013 Mar 25 PMID: 23528916 11 Bazot M, Bharwani N, Huchon C, et al European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis Eur Radiol 2017;27:2765–75 https://doi org/10.1007/s00330-016-4673-z 12 Guerriero S, Condous G, van den Bosch T, Valentin L, Leone FPG, Van Schoubroeck D, Exacoustos C, Installé AJF, Martins WP, Abrao MS, Hudelist G, Bazot M, Alcazar JL, Gonỗalves MO, Pascual MA, Ajossa S, Savelli L, Dunham R, Reid S, Menakaya U, Bourne T, Ferrero S, Leon M, Bignardi T, Holland T, Jurkovic D, Benacerraf B, Osuga Y, Somigliana E, Timmerman D. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group Ultrasound Obstet Gynecol 2016;48:318–32 https://doi.org/10.1002/uog.15955 13 National institute for health and care excellence guideline, endometriosis: diagnosis and management, 2017 Overview | Endometriosis: diagnosis and management | Guidance | NICE 14 Obstetrics and Gynaecological Society of Malaysia, Clinical Guidelines for the Management of Endometriosis, 2016 https://www.ogsm.org.my/docs/Endometriosis-guideline.pdf 15 Turkish Endometriosis and Adenomyosis Society Guidelines, Diagnosis and management of endometriosis, 2014 Microsoft Word - Guideline english final.docx (endometriozisdernegi.org) 16 Ulrich U, Buchweitz O, Greb R, Keckstein J, von Leffern I, Oppelt P, Renner SP, Sillem M, Stummvoll W, De Wilde RL, Schweppe KW, German and Austrian Societies for Obstetrics and Gynecology National German guideline (S2k): guideline for the diagnosis and treatment of endometriosis: long version – AWMF Registry No 015-045 Geburtshilfe Frauenheilkd 2014;74(12):1104–18 https://doi.org/10.1055/s-0034-1383187 PMID: 26157194; PMCID: PMC4470398 17 Federation of Obstetrics & Gynecological Societies of India, Good Clinial Practice Recommendations on Endometriosis, 2016 https://www.fogsi.org/wp-content/ uploads/2017/01/GCRP-2017-final.pdf 18 Björk E, Gustavsson M, Palmstierna M, Valentin A, Olovsson M, Melin AS. Nationellt vårdprogram för bättre och jämlik vård vid endometrios [Endometriosis - new clinical guidelines for better and equal care in Sweden] Lakartidningen 2020;117:19231 Swedish PMID: 32542617 19 Hirata T, Koga K, Kai K, Katabuchi H, Kitade M, Kitawaki J, Kurihara M, Takazawa N, Tanaka T, Taniguchi F, Nakajima J, Narahara H, Harada T, Horie S, Honda R, Murono K, Yoshimura K, Osuga Y. Clinical practice guidelines for the treatment of extragenital endometriosis in Japan, 2018 J Obstet Gynaecol Res 2020;46:2474–87 https://doi.org/10.1111/ jog.14522 20 Hwang H, Chung YJ, Lee SR, Park HT, Song JY, Kim H, Lee DY, Lee EJ, Kim MR, Oh ST. Clinical evaluation and management of endometriosis: guideline for Korean patients from Korean Society of Endometriosis Obstet Gynecol Sci 2018;61(5):553–64 https://doi org/10.5468/ogs.2018.61.5.553 Epub 2018 Sep PMID: 30254991; PMCID: PMC6137012 21 Cooperative Group of Endometriosis, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association [Guideline for the diagnosis and treatment of endometriosis] Zhonghua Fu Chan Ke Za Zhi 2015;50(3):161–169 Chinese PMID: 26268404 22 Federación Mexicana de Colegios de Obstetricia y Ginecología Diagnóstico y trata miento de endometriosis [Diagnosis and treatment of endometriosis] Ginecol Obstet Mex 2011;79(11):697–710 Spanish PMID: 22168117 23 Basta A, Brucka A, Górski J, Kotarski J, Kulig B, Oszukowski P, Poreba R, Radowicki S, Radwan J, Sikora J, Skret A, Skrzypczak J, Szyłło K, Polish Gynocologic Society Experts Group Stanowisko Zespołu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczace 44 Recent Guidelines on Endometriosis and Adenomyosis 601 diagnostyki i metod leczenia endometriozy [The statement of Polish Society’s Experts Group concerning diagnostics and methods of endometriosis treatment] Ginekol Pol 2012;83(11):871–6 Polish PMID: 23379199 24 Ministry of Health Diagnosis and Management of Endometriosis in New Zealand Wellington: Ministry of Health; 2020 25 South African guideline for treatment of endometriosis, 2017 https://sasreg.co.za/downloads/ Treatment-of-Endometriosis.pdf 26 Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, Vist GE, Falck-Ytter Y, Meerpohl J, Norris S, Guyatt GH. GRADE guidelines: Rating the quality of evidence J Clin Epidemiol 2011;64(4):401–6 https://doi.org/10.1016/j.jclinepi.2010.07.015 Correction to: Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan Engin Oral Correction to: Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan https://doi.org/10.1007/978-3-030-97236-3 Chapter in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_5 The ORCID id of the author was missed in the original publication and is provided here Khaleque N Khan: 0000-0002-9493-3340 The updated version of the chapters can be found at https://doi.org/10.1007/978-3-030-97236-3_5 https://doi.org/10.1007/978-3-030-97236-3_8 https://doi.org/10.1007/978-3-030-97236-3_16 https://doi.org/10.1007/978-3-030-97236-3_23 https://doi.org/10.1007/978-3-030-97236-3_26 https://doi.org/10.1007/978-3-030-97236-3_31 https://doi.org/10.1007/978-3-030-97236-3_35 https://doi.org/10.1007/978-3-030-97236-3_36 https://doi.org/10.1007/978-3-030-97236-3_37 https://doi.org/10.1007/978-3-030-97236-3_39 https://doi.org/10.1007/978-3-030-97236-3_40 https://doi.org/10.1007/978-3-030-97236-3_42 https://doi.org/10.1007/978-3-030-97236-3_43 https://doi.org/10.1007/978-3-030-97236-3_44 © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 E Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_45 C1 C2 E Oral Chapter in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_8 The ORCID ids of the authors were missed in the original publication and are provided here Jorg Keckstein: 0000-0002-3943-3300 Peter Oppelt: 0000-0003-3852-5948 Gernot Hudelist: 0000-0002-9424-2208 Chapter 16 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_16 Dr Hanan Alsalem’s name was misspelled in the initial publication as Hanan Amsalem and has been corrected in all further publications Chapter 23 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_23 The ORCID ids of the authors were missed in the original publication and are provided here Marina Kvaskoff: 0000-0002-4557-3772 Stacey A. Missmer: 0000-0003-3147-6768 Chapter 26 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_26 The ORCID ids of the authors were missed in the original publication and are provided here Maurizio N. D'Alterio: 0000-0001-9874-1488 Stefano Angioni: 0000-0002-2314-0028 Fabio Ghezzi: 0000-0003-3949-5410 Antoni Simone Laganà: 0000-0003-1543-2802 Chapter 31 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_31 The ORCID id of the authors was missed in the original publication and is provided here Silvia Vannuccini: 0000-0001-5790-587X Chapter 35 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_35 The ORCID ids of the authors were missed in the original publication and are provided here Harald Krentel: 0000-0002-1238-9207 Maribel Acien: 0000-0002-6536-453X Chapter 36 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_36 The ORCID id of the author was missed in the original publication and is provided here Correction to: Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan C3 Yasushi Hirota: 0000-0003-0241-9780 Chapter 37 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_37 The ORCID ids of the authors were missed in the original publication and are provided here Jwal Banker: 0000-0001-6637-1398 Manish Banker: 0000-0001-9918-1128 Chapter 39 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_39 The ORCID id of the author was missed in the initial publication and is provided here Harald Krentel: 0000-0002-1238-9207 Chapter 40 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_40 The ORCID ids of the authors were missed in the original publication and are provided here Dr Hiroaki Komatsu: 0000-0002-4507-6848 Fuminori Taniguchi: 0000-0001-6922-0632 Tasuku Harada: 0000-0002-1492-7275 Chapter 42 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_42 The ORCID ids of the authors were missed in the original publication and are provided here Simone Ferrero: 0000-0003-2225-5568 Fabio Barra: 0000-0003-4117-6603 Chapter 43 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_43 The ORCID id of the author was missed in the initial publication and is provided here Sanjay Agarwal: 0000-0002-8046-9807 Chapter 44 in: E. Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3_44 The ORCID id of the author was missed in the initial publication and is provided here Nura Fitnat Topbas Selcuki: 0000-0002-5749-9987 Index A Abdominal wall endometriosis (AWE), 244 Abnormal uterine bleeding (AUB), 489–494 Accessory and cavitated uterine masses (ACUM), 474, 483 Activin, 432 Acupuncture, 342 Adenomyoma, 6, See also Adenomyosis Adenomyosis, 60, 111, 145, 146, 149, 218, 400–402, 407 adolescence diagnosis, 482, 483 incidence, 481 juvenile cystic adenomyomas, 483, 484 medical treatment, 485, 486 surgical treatment, 484, 485 aromatase inhibitors, 568, 569 biomarker-based diagnosis, 404 classification and staging, 405, 406 ectopic endometrial glands and stroma, 441 histology and symptoms, 445–447 metaplastic process, 442 MRI and ultrasound, 442–445 prevalence, 442 clinical diagnosis, 402 danazol, 567, 568 definition, 424, 489 endometrial cancer, 517, 519, 520 fertility and ART causing infertility, 501, 502 definition, 499 FAOM, 500 medical management, 505, 506 pregnancy outcomes, 502, 503 surgical management, 507 treatment options, 500 types, 500 fertility outcomes, 512 GnRH agonists, 580 guidelines, 598, 599 heterotopic endometrial glands, 400 history of, 411, 412 classes, 412 comprehensive definition, 414 Cullen, Thomas, 414–417 cullen’s theory, 414 cystic myoma, 412 cystofibroma, 412 Frankl, Otto, 417, 418 glandular structures, 413 glandular tissue, 413 malignant degeneration, 412 mesonephric origin, 413 reluctance, 414 imaging diagnosis, 403, 404 magnetic resonance imaging adenomyoma, 478 diagnosis, 472 direct signs, 474 indirect signs, 475, 477 junctional zone, 477, 478 role of, 471, 472 technical requirements, 478 uterine zonal anatomy, 472, 473 malignant transformation, 518, 519 mapping, 405 neonatal outcomes, 514 obstetrical outcomes, 513, 514 oral contraceptives, 526, 527 pain and AUB at elder reproductive age, 491–494 symptoms, 490 at younger reproductive age, 491 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 E Oral (ed.), Endometriosis and Adenomyosis, https://doi.org/10.1007/978-3-030-97236-3 603 Index 604 Adenomyosis (cont.) pathogenic mechanisms angiogenesis, 434 genetics and epigenetics, 427, 428 immune response, 430, 431 inflammation, 430 migration, invasion and fibrosis, 432, 433 neurogenic factors and neurogenesis, 434, 435 pituitary hormones function, 429 proliferation and cell survival, 431, 432 steroid hormones, 428, 429 pathogenic theories endometrium, 426 metaplasia, 426, 427 pregnancy outcomes, 513 progestins, 547, 548 risk factors, 424–426 stroma embedded, 400 symptomatic adenomyosis, 494, 495 ultrasonography diagnosis, 452, 462–464 endometriosis, 464, 465 evaluation and description, 458, 459 MRI, 464 myometrial layers location, 460, 461 phenotypes, 451 quality of, 452 size and extension, 461, 462 symptoms, 465, 466 TVS uterine wall location, 460 2D TVS features, 452–455 3D TVS features, 456, 457 type of, 460 uterine myometrium, 518 young women, 406 Adnexal assessment, 112–113 α-granules, 44 American college of obstetricians and gynecologists (ACOG), 548, 549 American society for reproductive medicine (ASRM) staging system, 25, 95, 192, 550 Anastomotic leakage (AL), 213 Angiogenesis, 434 Antagonists, 169–170 Antenatal ultrasound, 149 Antral follicle count (AFC), 272 Arachidonic acid (AA), 330 Archimetriosis, 200 Aromatase inhibitors, 560, 565–569 Aromatase P450, 558 Assisted reproductive technology (ART), 381, 493 Asymmetrical myometrium thickening, 111 Atypical endometriosis, 300 Autoimmune thyroid disorder, 160 B B cell lymphoma (Bcl-2) protein, 432 17β-hydroxysteroid-dehydrogenase (17β-HSD-2), 86, 537 Bladder lesions, 230 Bladder pain syndrome (BPS)/interstitial cystitis, 126, 128 Bone marrow-derived stem cells (BMDSCs), 36 Bowel endometriotic nodules, 118 Breast cancer, 289 Bulun’s feed-forward model, 49 C Celiac disease, 160 Chest X-ray (CXR), 247 Chronic inflammation, 200 Chronic pain, 203, 205 Chronic pelvic pain, 126, 310 Clinical stereotypes, 19 Coelomic metaplasia, 32, 35 Combined hormonal contraceptives (COCs), 166, 320 Combined oral contraceptive pill (COCP), 542 Combined oral contraceptives (COCs), 202, 356, 357, 425 Complementary and alternative medicine (CAM), 338 Complementary health approaches (CHAs), 338 Controlled ovarian stimulation (COS), 272 Cost-effectiveness, 376, 378 COX-2, 430 C-reactive protein (CRP), 330 Cross organ sensitization, 127 Cryopreservation, 280 Cryptoxanthin, 332 Cyclical pelvic pain, Cyclic bleeding, 44 Cyproterone acetate (CPA), 540 Cystic adenomyoma, 407 Cystic juvenile adenomyosis, 474 Cystoscopy, 131 D Danazol, 533, 558–565, 567, 568 Deep endometriosis (DE), 48, 208, 236 Deep endometriotic nodules, Index Deep infiltrating endometriosis (DIE), 110, 181, 313, 318 Dense granules, 44 Depot injections, 540, 541 Depot medroxyprogesterone (DMPA), 167, 540, 541 Desogestrel, 167 Dienogest (DNG), 538, 539 Diindolylmethane (DIM), 335 Disc excision, 210 Discoid resection (DR), 212 Downregulation of 17-ßHSD-2, 86 Drospirenone, 167 Dydrogesterone, 540 Dysmenorrhea, 161, 202, 310, 526, 543, 548 Dyspareunia, 208, 310, 313 E Ectopic lesions, 87 Education, 356 Elagolix, 586 Electromyography, 261 Empiric gonadotropin-releasing (GnRH) agonists, 162 Endocervix, 147 Endocoagulation, 165 Endometrial cancer, 289, 519, 520 Endometrial cancer arising in adenomyosis (EC-AIA), 518–520 Endometrial maturation, 148 Endometrial-myometrial interface (EMI), 401 Endometrial-myometrial interface disruption (EMID), 200 Endometrioma, 192, 194, 301, 304 clinical repercussions, 275–278 COS protocol, 278–280 cryopreservation, 280 ovarian reserve, 274, 275 poor oocyte quality, 273, 274 Endometriosis, 60, 75, 85, 180, 187, 199, 218, 271, 286, 309, 310, 362 activation of transformation, 30 adenomyosis, 6–7 in adolescents, 527, 528 clinical presentation, 158–160 combined hormonal contraception, 166 endometriosis lesions, 163, 164 evaluation, 160, 161 exogenous androgens, 168 follow-up, 171 GnRH agonists, 169 GnRH antagonists, 170 laparoscopy, 163 605 multidisciplinary and holistic management, 170 non-hormonal therapies, 170 pathophysiology, 157, 158 postoperative medical therapies, 166 prevalence and epidemiology, 156 progestin-only therapies, 167, 168 risk factors, 156–157 surgical treatment, 164–166 transmasculine adolescents, 168 trial of medical therapy, 162, 163 AFS/rASRM classification, 94 annual incidence rates, 20, 21 aromatase inhibitors, 560, 565–567, 570–572 aromatase P450, 558 asymptomatic patient, 224 biomarkers, 192, 372, 373 cancer, 294, 295 cell of origin acquired Müllerian disease, 36 activation, transition and inactivation, 33 BMDSCs, 36 coelomic metaplasia, 35 extension of tubal epithelium, 33–34 Müllerian and non-Müllerian cells, 31 Müllerian cells of origin, 32 Müllerian cellular rests, 34 Müllerian cellular rests, 34 non-Müllerian cells of origin, 32 ovarian germinal epithelium, 33 simple nodulectomy, 30 tertiary pediatric referral practice, 30 theoretical concerns, 31–32 wolffian (mesonephric) duct remnants, 35 cervical cancer, 290, 291 chocolate cysts, chronic, 188 classification systems, 95, 192 colorectal cancer, 290 concomitant immune dysfunction, 532 confounding, 292 costs, 366 cyclical pelvic pain, danazol, 558–565 deep endometriosis, 207 deep endometriotic nodules, deep infiltrating, 182 definition, 531 diagnosis, 16, 191, 192, 220, 366–372, 596, 597 diagnosis delay, 188 606 Endometriosis (cont.) differential diagnosis, 193, 368 dilemma for epidemiology, 16 disc excision, 210, 211 discovery of adenomyosis, EFI, 97–99 emotional impact, 312, 313 ENZIAN classification, 99–101 epidemiology, 20, 188 epithelial cells, estrogen-dependent disease, 218 estrogenic stimulation, 30 etiology, 532 fertility, 221 fertility index, 183 GnRH agonists, 580, 581 GnRH analogs, 532 GnRH antagonists, 586–588 guidelines, 593–595 gynaecological cancers, 207, 287–289 heterogeneity, 293 hormone replacement therapy, 223 hospital admissions, 380 hysterectomies, 15 identification of, imaging, 373, 374 immune dysfunction, 30 impacts, 364, 365 indirect costs associated, 382–384 individual determinants of diagnosis, 17–18 infertility, 4, 180, 190, 545, 546, 598 in situ development, 30 limitations, 386–388 malignant transformation, 224–226 medical therapies, 375 medical treatment, 534–535, 597 medication, 533 meta-analysis, 291 methodology, 595, 596 methods of dissemination direct extension, 38 embryonic development, 38 hematogenous dissemination, 37 lymphatic dissemination, 37 retrograde menstruation theory, 36, 37 surgical transplantation, 38 microscopic examination, monitoring recommendations, 295, 296 national economic burden, 384, 385 non-ovarian endometriosis, NSAIDs, 532 ovarian endometrioma, 8, 183 pain problems, women, 222 pain symptoms, 532 Index pathogenesis, 189 pathophysiological mechanisms, 189, 219, 220, 293 perforating hemorrhagic cysts, 10 peritoneal, 181 phenotypes, 7, postoperative hormonal suppression, 546 prevalence, 179, 218, 363 classification of, 25 diagnosis, 25 geographical variations in prevalence, 23–24 hospital/clinic samples, 21–22 hospital records/insurance claims databases, 22 population-based australian study, 24, 25 self-reported endometriosis, 22–23 surveillance of, 24 prevention recurrence, 532 primary prevention, 354, 355 progestins, 533 ACOG, 548, 549 ASRM, 550 classification, 535 COCs, 533 CPA, 540 depot injections, 540, 541 dienogest, 538, 539 dydrogesterone, 540 ESHRE, 548, 549 hypoestrogenic status, 533 intrauterine system, 541 mechanism of action, 536 MPA, 540 NETA, 539 NICE, 548 route of administration, 538 side effects, 542 SOGC, 549 subdermal implants, 541 target tissue, 537, 538 tissue remodeling, 533 WES, 549 pseudo-uterus, 10 publication bias, 293 quality of life assessment, 310–312, 317–319 rASRM score, 94–97 rectal endometriosis, 104 rectal shaving, 208–210 rectovaginal endometriosis, 544 rectovaginal nodules, risk factors, 189, 190 secondary prevention, 355, 356 Index sexuality, 313–317, 319–322 signs and symptoms, 363, 364 skin cancer, 290 social and medical constructions, 18–19 socio-economic, cultural and political context, 19–20 study robustness, 292 superficial peritoneal lesions, surgical classification, 103 surgical treatment, 597, 598 symptom of cyclical pain, symptoms, 18 temporality, 291 tertiary prevention, 356 thyroid cancer, 290 treatment, 180, 193–195, 221, 376–379, 525, 526 treatment for pain, 542–544 TVS imaging of adenomyosis, 104 Endometriosis diagnostic modalities adnexal assessment, 112–113 deep endometriosis assessment, 114–119 gel sonovaginography, 119 MRI, 122 ovarian position assessment, 113, 114 pouch of douglas assessment, 113–114 rectal water-contrast transvaginal ultrasonography, 119–121 tenderness-guided transvaginal ultrasonography, 119 three-dimensional ultrasonography, 120–122 uterus assessment, 111–112 Endometriosis fertility index (EFI), 25, 94, 97–99, 382 Endometriosis genetic susceptibility variants, 76 Endometriosis lesions, 163, 164 Endometriosis-associated malignancies (EAMs), 300, 301 Endometriosis-associated ovarian carcinoma (EAOC), 300 Endometriosis-associated pain, 200, 201 Endometriotic foci, 537 Endometriotic nodule of uterosacral ligament, 117 Endomyometriosis, 407 Endosalpinx, 147 Endothelial-mesenchymal transition (EndoMT), 48 End-to-end anastomosis (EEA), 210, 211 Enzian classification, 94, 99–104 Enzian scoring system, 101 Epigallocatechin Gallate (EGCG), 340 Epithelial cells, 607 Epithelial ovarian cysts, 33 Epithelial to mesenchymal transition (EMT), 63, 432, 433 Estrogen-dependent disease, 85 Estrogen threshold hypothesis (ETH), 583, 584 European Endometriosis League (EEL), 355 European society of human reproduction and embryology (ESHRE), 548, 549, 595 Eutopic endometria, 64 Excision, 165 Exogenous androgens, 168 Extrapelvic endometriosis, 243, 244 abdominal wall, 244 abdominal wall endometriosis, 244, 245 thoracic endometriosis syndrome, 246, 247 visceral, 246 F Fan shaped shadowing, 111 Fatty acids, 335 Femoral nerve endometriosis, 259 Fertility preservation (FP), 272, 273 Fibroblast-to-myofibroblast transdifferentiation (FMT), 63 Focal adenomyosis of the outer myometrium (FAOM), 500 Focal adhesion kinase (FAK), 433 Follicle-stimulating hormone (FSH), 169 Follistatin, 432 G Gel sonovaginography, 119 Genome-wide association study (GWAS), 76–78 Gestational hypertension, 231 Glandular glycogen, 147 Gonadotropin-releasing hormone (GnRH), 68, 69 Gonadotrophin-releasing hormone agonists (GnRHa), 169–170, 239, 336, 375, 525 add-back therapy, 581–583 adenomyosis, 580 amino acid substitution, 578–580 bone impact, 581 clinical uses, 578 empiric use of, 584 endometriosis, 580, 581 estrogen threshold hypothesis, 583, 584 physiology, 578 post-operative use, 584–586 therapy, 169 Index 608 GnRH antagonists, 170 endometriosis, 586–588 Goserelin, 568 Guideline development group (GDG), 595 Gycosaminoglycan (GAG) layer, 129 H Hematogenous dissemination, 37 Hemoperitoneum, 230 Hemorrhagic cysts, Hepatocyte growth factor (HGF), 58 Herlyn-Werner-Wünderlich syndrome (HWWS), 150 High antioxidant diet (HAD), 336 High-intensity focused ultrasound (HIFU), 493, 506 Hormonal imbalance, 86 Hormonal therapies, 162 Hormone replacement therapy, 223 Hormone withdrawal symptoms, 526 Hydrodistension, 132 Hyperestrogenism, 301, 354 Hyperperistalsis, 354 Hypersensitive bladder syndrome (HBS), 128 Hypovitaminosis D, 332 Hypoxia-inducible factor alpha (HIF-1A), 434 Hysterectomy, 230, 376, 378 I Immunological processes, 355 Impaired natural killer (NK) activity, 62 Inferior Gluteal nerve, 254 Infertility, 4, 188, 192 Inflammatory bowel disease, 160, 355 Insulin-like growth factor-1 (IGF-1), 334 International Deep Endometriosis Analysis (IDEA), 110 Interstitial cystitis/bladder pain syndrome (BPS), 128–132, 134, 135 Intrauterine insemination (IUI), 194 Intrauterine system, 541 In utero and early-life ectopic endometrial foci, 146–149 endometrial glands development, 147–148 perimenarcheal endometriosis, 150–151 In vitro fertilization (IVF), 195, 364 Irritable bowel syndrome (IBS), 126, 138, 139, 205, 332 J Junctional zone (JZ), 199, 426 Juvenile cystic adenomyomas, 483, 484 K Karnaky’s theory, 31 Kissing ovaries, 114 L Laparoscopy, 110, 163, 192, 363, 379 Laser ablation, 165 Letrozole (LTZ), 560, 565, 566 Leukemia inhibitory factor (LIF), 501 Levonorgestrel-containing intrauterine system, 533 Levonorgestrel intrauterine system (LNG- IUS), 167, 222, 598 Levonorgestrel-releasing intrauterine device (LNG-IUD), 381, 550 Lipopolysaccharide (LPS), 59, 60 Low anterior resection syndrome (LARS), 213 Low-dose estrogen plus progestin (LEP), 526, 527 Luteinizing hormone (LH), 169 Lymphatic dissemination, 37 Lynch syndrome, 304 Lysosomes, 44 M Macrophages (Mφ) early and advanced endometriosis, 63–66 endometrial and peritoneal mesothelial cells, 58 ER/PR expression, 67 eutopic and ectopic endometrium, 64 fibrogenesis in endometriosis, 62–63 functional endometrium, 57 fundamentals of, 58–59 GnRH, 68, 69 HGF expression/MVD, 65–66 infiltration, 65 inflammation and ovarian steroids, 68 innate immune cells, 58, 60–63 mesenchymal cells, 58 NK cells, 61–62 phases of menstrual cycle, 64 regulation of HGF, 66 role of, 61–62 Magnetic resonance imaging (MRI), 122, 208, 236 Index Mφ infiltration, 64, 65 Malignant transformation, 219, 221 Mayer-Rokitansky-Kuster-Hauser syndromes, 426 McKusick-Kaufman syndrome, 150, 158 Medroxyprogesterone acetate (MPA), 540 Menopausal endometriosis, 224 Menstruation stigma, 18 Mesenchymal stem cells, 151 Mesothelial-mesenchymal transition (MMT), 48 Meta-analysis, 291 Metalloproteinases (MMPs), 330 Metaplasia theory, 426, 427 Micro-vessel density (MVD), 65, 434 Microwave endometrial ablation (MEA), 493 Miniature uteri, 200 mRNA expression, 501 Müllerian cells of origin, 32, 34 Müllerian ducts, 146 Multiple sclerosis, 160 Myostatin, 432 N National institute for health and care excellence (NICE), 548 Nearest gene assumptions, 78 Neonatal uterine bleeding (NUB), 148, 150 Nerve growth factor (NGF), 435 Nerve-sparing, 321 Neurogenic inflammation, 203 Neuromuscular electrical stimulation (NMES), 343 NK cell cytotoxicity, 45–47, 62 N-methyl-D-aspartate (NMDA) receptor, 127 Nociceptive pain, 203 Noncyclic pelvic pain, 543 Non-hormonal therapies, 170 Non-Müllerian cells of origin, 32 Non-steroidal anti-inflammatory drugs (NSAIDs), 162, 202, 336 Norethindrone, 167 Norethisterone (norethindrone) acetate (NETA), 539 Nutritional interventions acupuncture, 342, 343 antioxidant diet, 335, 336 CAM, 338 Chinese medicine decoctions, 338, 339 fatty acids, 335 FODMAP, 337 herbal extracts therapies, 340, 341 herbal medicines, 339, 340 osteopathy, 343, 344 vitamin D, 335 609 O Obstetrics, 230 Obturator nerve endometriosis, 254, 259 Oral contraceptives (OC) Adenomyosis, treatment, 526, 527 endometriosis in adolescents, 527, 528 treatment, 525, 526 LEP, 527 Osteopathy, 343 Ovarian cancer, 287 Ovarian cystosarcoma, Ovarian endometriomas (OE), 8, 48, 165 Ovarian endometriosis, 182, 183 Ovarian germinal epithelium, 33 Ovarian hematomas, Ovarian reserve, 194, 195 Oxidative stress, 335 P Painful bladder syndrome (PBS), 128 Pain management, 240, 241 Palmitoylethanolamide (PEA), 341 Parametritis nodosa posterior, Pelvic nerve endometriosis, 252, 267 basic pelvic neuroanatomy, 253 diagnosis, 259, 260 etiology, 253 femoral nerve, 259 imaging, 261, 262 medical treatment, 264 natural course, 263 non-discogenic sciatica, 255 obturator nerve, 259 pathophysiology, 253 sacral plexus endometriosis, 256, 257 sciatic nerve, 257, 258 surgical treatment, 265–267 Pelvic pain, 527 Pelvic symptoms, 191 Pelvis endometriosis, 35 Pentosan polysulfate (PPS), 132 Perforating hemorrhagic cysts, 10 Perimenarcheal endometriosis, 150–151 Peripartum hysterectomy, 231 Peripheral blood mononuclear cells (PBMCs), 60, 63 Peritoneal endometriosis, 181 Peritoneal fluid (PF), 58 Phytoestrogens, 333 Pituitary hormones function, 429 Placenta previa, 231 Plasma energy, 209 610 Platelets angiogenesis, 43 bioactive molecules, 44 cytotoxicity in NK cells, 45–47 epigenetic aberration, 43 estrogen production, 48–49 even cancer-driver mutations, 43 granules, 44 hypercoagulability, 49–50 inflammation, 43 ovarian steroid receptor, 48–49 progression of endometriotic lesions, 47–48 resistance to apoptosis, 43 role of, 44, 45 therapeutic implications, 50 thrombin/thomboxane, 45 Polypoid adenomyoma (PA), 407 Posterior femoral cutaneous nerve, 254 Posterior vaginal fornix endometriotic nodule, 117 Postmenopausal endometriosis, 218 Potassium sensitivity test, 131 P450 (P450arom) protein, 501 Precancerous lesion, 300 Precursor lesion, 300 Pregnancy, 230 Premature placental abruption, 231 Prematurity, 231 Prepubertal menstruation, 148 Primary prevention, 353, 354 Primum movens, 429 Progesterone, 533 Progesterone resistance altered steroid receptor, 87–88 progestin therapy, 88–89 treatment options, 89–91 Progesterone signaling, 86 Progestin-only therapies, 167, 168 Pro-inflammatory cytokines, 59 Prolactin (PRL), 429 Proliferator-activated receptor gamma (PPAR-γ), 333 Prostaglandin (PG), 527 biosynthesis, 355 Psychology, 309 Pudendal nerve, 254 Q Quality of life (QoL), 207, 309–311 Index R rASRM classification, 95, 97 rASRM endometriosis, 95 Rectal shaving, 212 Rectal water-contrast transvaginal ultrasonography, 119–121 Rectovaginal septum nodule, 116 Recurrence and non-responders, 90 Recurrent endometriosis, 236 management, 240 mechanisms, 237 prevention, 238, 239 risk factors, 238, 239 timing, 237, 238 Reproductive age, 21 ReTIAR prism, 48 Retrograde menstruation, 145 model, 37 theory, 36, 37 Rheumatoid arthritis, 159–160 S Sacral nerves, 254 Sacral plexus endometriosis, 256 Sampson’s theories, 37 Sciatic nerve (SN), 255 Secondary prevention, 354 Segmental resection (SR), 212 Self-reported endometriosis, 22–23 Sex steroid hormones function, 428, 429 Single nucleotide polymorphisms (SNPs), 76 Sjögren’s syndrome, 159 Sliding sign, 113 Smooth muscle metaplasia (SMM), 47, 63 Social functioning, 309 Society of obstetricians and gynaecologists of Canada (SOGC), 549 Soft markers, 113 SonoPODography (SPG), 374 Spastic pelvic floor syndrome, 135–138 Spinal hyperalgesia, 204 Spontaneous hemoperitoneum in pregnancy (SHiP), 230 Sporadic ectopic staining, 149 Steroidogenic acute regulatory protein (StAR), 48, 219 Subdermal implants, 541 Sub-phenotype genome-wide association analyses, 78 Superficial peritoneal lesions, Superior gluteal nerve, 254 Index T Tenderness-guided transvaginal ultrasonography, 119 Thoracic endometriosis syndrome (TES), 246 Three-dimensional ultrasonography, 120–122 Tissue injury, 199 Tissue injury and repair (TIAR) theory, 426 Toll-like receptor (TLR4), 70 Toll-like receptors (TLRs), 61 Traditional Chinese medicine (TCM), 342 Transabdominal ultrasonography (TAS), 245 Transcutaneous electrical nerve stimulation (TENS), 343 Transmasculine adolescents, 168 Transvaginal sonography (TVS), 189, 208 Transvaginal ultrasound (TVU), 110, 301, 403 U Ultrasonography, 191, 356 Urogenital ridge, 146 611 Uterine artery embolization (UAE), 493, 506 Uterine gland, 147 Uterine leiomyoma, 60 Uterus like mass (U-LM), 407 V Vaginal bleeding, 148 Vesico-uterine pouch, 114 Video-assisted thoracoscopic surgery (VATS), 247 Visceral endometriosis, 246 Visual-analogue scale (VAS), 318 Vitamin D, 335 von-Willbrand factor (VWF), 66 W Well-being, 310, 316, 318, 319 World endometriosis society (WES), 549 Wound healing, 49