Clinical diagnosis of endometriosis: a call to action Sanjay K. Agarwal, MD; Charles Chapron, MD; Linda C. Giudice, MD, PhD; Marc R. Laufer, MD; Nicholas Leyland, MD; Stacey A. Missmer, ScD; Sukhbir S. Singh, MD; Hugh S. Taylor, MD E ndometriosis has such wide- ranging and pervasive sequelae that it has been described as “nothing short of a public health emergency” requiring immediate action. 1 Population-based data suggest that more than 4 million reproductive-age women have diagnosed endometriosis in the United States. 2 As daunting as this number is, it only tells part of the story, as an estimated 6 of 10 endometriosis cases are undiagnosed. 3 Thus more than 6 million American women may expe- rience repercussions of endometriosis without the benefit of understanding the cause of their symptoms or appropriate management. When discussing the patient’ s experi- ence with endometriosis, pain and infertility are usually of greatest concern, as they are 2 of the disease’ s more com- mon symptoms. However, the real toll is even greater: women with endometriosis experience diminished quality of life, increased incidence of depression, adverse effects on intimate relationships, limitations on participation in daily ac- tivities, reduced social activity, loss of productivity and associated income, increased risk of chronic disease, and significant direct and indirect healthcare costs. 4e8 Moreover, emerging data indi- cate that endometriosis is associated with greater risk of obstetric and neonatal complications. 9e12 The challenge of diagnosing endometriosis There are no pathognomonic features or biomarkers necessary and sufficient to define endometriosis. Rather, key symptoms that currently prompt surgi- cal evaluation, such as pain and infer- tility, can have multiple causes. Endometriosis is typically defined by its histology: extrauterine lesions consisting of endometrial glands, endometrial stroma, and/or hemosiderin-laden macrophages. Based on location and depth, lesions are further described as superficial peritoneal lesions, ovarian endometrioma, or deep endometriosis. However, the presence of lesions does not preclude other etiologies for the THE PROBLEM: Endometriosis is undiagnosed in a large proportion of affected women, resulting in ongoing and progressive symptoms with associated negative impacts on health and well-being. Current practice standards, which rely primarily on laparoscopy for a definitive diagnosis before beginning therapy, frequently result in prolonged delay between symptom onset, diagnosis, and subsequent treatment. A SOLUTION: Enhanced use of clinical diagnostic techniques may reduce the delay in time to diagnosis and hence bring more rapid relief to affected patients, limit disease pro- gression, and prevent sequelae. From the Center for Endometriosis Research and Treatment (Dr Agarwal), University of California San Diego, La Jolla, CA; Université Paris Descartes (Dr Chapron), Sorbonne Paris Cité, Faculté de Médecine, Assistance PubliqueHôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France; Department of Obstetrics, Gynecology and Reproductive Sciences (Dr Giudice), University of California, San Francisco, CA; Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital; Department of Obstetrics, Gynecology, and Reproductive Biology (Dr Laufer), Brigham and Women’s Hospital and Harvard Medical School; Division of Gynecology, Boston Children’s Hospital and Harvard Medical School, Boston, MA; Department of Obstetrics and Gynaecology (Dr Leyland), McMaster University, Hamilton, Ontario, Canada; Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital; Department of Epidemiology, Harvard T.H. Chan School of Public Health (Dr Missmer), Boston, MA; and Department of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University, Grand Rapids, MI; Department of Obstetrics and Gynaecology (Dr Singh), University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Obstetrics, Gynecology, and Reproductive Sciences (Dr Taylor), Yale School of Medicine, New Haven, CT. Received Aug. 24, 2018; revised Dec. 21, 2018; accepted Dec. 31, 2018. S.K.A. is a consultant for and has received research support from AbbVie. C.C. is consultant for Ipsen, Bayer, AbbVie, and Gedeon Richter. He is an advisor/consultant for AbbVie, Bayer, Ipsen, and Gedeon Richter Preglem. L.C.G. is a consultant for AbbVie, Myovant Sciences, ForEndo Pharma, NextGen Jane, and Merck. M.R.L. is a consultant for AbbVie and NextGen Jane. N.L. is a consultant for and has received research support from AbbVie, Allergan, and the Canadian Institutes for Health Research. S.A.M. is a consultant for AbbVie, Oratel Diagnostics, and Celmatix, and receives research support from the National Institutes of Health and the Marriott Family Foundations. S.S.S. is a consultant for and has received research support from AbbVie, Bayer, and Allergan. H.S.T. is a consultant for AbbVie, Bayer, Obseva, OvaScience, ForEndo, and DotLab. Support for the development of this manuscript was provided by AbbVie, Inc. AbbVie had the opportunity to review the final manuscript draft, but the manuscript content was solely at the discretion of the authors and reflects the opinions of the authors. The authors received no direct compensation for their efforts. Corresponding author: Hugh S. Taylor, MD. hugh.taylor@yale.edu 0002-9378 ª 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). https://doi.org/10.1016/j.ajog.2018.12.039 354 American Journal of Obstetrics & Gynecology APRIL 2019 Call to Action ajog.org