Understanding Ultrasound Features that Predict Symptom Severity in Patients with Adenomyosis: a Systematic Review

Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear which criteria reflect the severity of symptoms. The aim of this review is to summarize the ultrasound features that correlate with clinical manifestations of adenomyosis and to discuss diagnostic methods for predicting disease severity. A literature search of PubMed and Google Scholar published up to March 2022 was performed. A consensus-based classification was determined primarily by defining the mapping or topography of the lesion. Ultrasound features can be classified into direct (i.e., the presence of ectopic endometrial tissue within the myometrium) and indirect findings (i.e., changes in the myometrial structure and translesional vascularity secondary to myometrial invasion). There are some reports that symptoms are positively correlated with the location and spread of the disease. Indeed, the lesion thickness, diffuse or internal adenomyosis, and focal adenomyosis may be associated with increased risks of dysmenorrhea, abnormal uterine bleeding, and infertility, respectively. Two ultrasound markers (i.e., the presence of heterogeneous myometrium and myometrial cysts) appear to be the criteria most clinicians focus on. However, decision-making on treatment necessity is determined by symptom severity rather than the topography of the lesions. There is currently no consensus that symptom severity can be predicted based on ultrasound features, but the ultrasound-based criteria may be helpful in diagnosing adenomyosis. Similar content being viewed by others Data Availability No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998;4:312–22. Protopapas A, Grimbizis G, Athanasiou S, Loutradis D. Adenomyosis: disease, uterine aging process leading to symptoms, or both? Facts Views Vis Obgyn. 2020;12(2):91–104. Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, et al. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol. 2022;60(1):118–31. Van den Bosch T, Dueholm M, Leone FP, Valentin L, Rasmussen CK, Votino A, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015;46(3):284–98. Van den Bosch T, de Bruijn AM, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, et al. Sonographic classification and reporting system for diagnosing adenomyosis. Ultrasound Obstet Gynecol. 2019;53(5):576–82. Van den Bosch T, Van Schoubroeck D. Ultrasound diagnosis of endometriosis and adenomyosis: state of the art. Best Pract Res Clin Obstet Gynaecol. 2018;51:16–24. Champaneria R, Abedin P, Daniels J, Balogun M, Khan KS. Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy. Acta Obstet Gynecol Scand. 2010;89(11):1374–84. Kobayashi H. Molecular targets for nonhormonal treatment based on a multistep process of adenomyosis development. Reprod Sci. 2023;30(3):743–60. Kobayashi H. Possible association between adenomyosis and disseminated intravascular coagulation and thromboembolism: a systematic review. World Acad Sci J. 2022;4(4). https://doi.org/10.3892/wasj.2022.162. Matsubara S, Kawaguchi R, Akinishi M, Nagayasu M, Iwai K, Niiro E, et al. Subtype I (intrinsic) adenomyosis is an independent risk factor for dienogest-related serious unpredictable bleeding in patients with symptomatic adenomyosis. Sci Rep. 2019;9(1):17654. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. Bazot M, Daraï E, Rouger J, Detchev R, Cortez A, Uzan S. Limitations of transvaginal sonography for the diagnosis of adenomyosis, with histopathological correlation. Ultrasound Obstet Gynecol. 2002;20(6):605–11. Dueholm M, Lundorf E. Transvaginal ultrasound or MRI for diagnosis of adenomyosis. Curr Opin Obstet Gynecol. 2007;19(6):505–12. Costello MF, Lindsay K, McNally G. The effect of adenomyosis on in vitro fertilisation and intra-cytoplasmic sperm injection treatment outcome. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):229–34. Kepkep K, Tuncay YA, Göynümer G, Tutal E. Transvaginal sonography in the diagnosis of adenomyosis: which findings are most accurate? Ultrasound Obstet Gynecol. 2007;30(3):341–5. Exacoustos C, Brienza L, Di Giovanni A, Szabolcs B, Romanini ME, Zupi E, et al. Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology. Ultrasound Obstet Gynecol. 2011;37(4):471–9. Kobayashi H, Matsubara S. A classification proposal for adenomyosis based on magnetic resonance imaging. Gynecol Obstet Investig. 2020;85(2):118–26. Celli V, Dolciami M, Ninkova R, Ercolani G, Rizzo S, Porpora MG, et al. MRI and adenomyosis: what can radiologists evaluate? Int J Environ Res Public Health. 2022;19(10):5840. Kishi Y, Suginami H, Kuramori R, Yabuta M, Suginami R, Taniguchi F. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. Am J Obstet Gynecol. 2012;207(2):114.e1–7. Rees CO, Nederend J, Mischi M, van Vliet HAAM, Schoot BC. Objective measures of adenomyosis on MRI and their diagnostic accuracy-a systematic review & meta-analysis. Acta Obstet Gynecol Scand. 2021;100(8):1377–91. Bourdon M, Oliveira J, Marcellin L, Santulli P, Bordonne C, Maitrot Mantelet L, et al. Adenomyosis of the inner and outer myometrium are associated with different clinical profiles. Hum Reprod. 2021;36(2):349–57. Gunther R, Walker C. Adenomyosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. 2022 Jan–. PMID: 30969690. Di Donato N, Montanari G, Benfenati A, Leonardi D, Bertoldo V, Monti G, Raimondo D, Seracchioli R. Prevalence of adenomyosis in women undergoing surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2014;181:289–93. Di Donato N, Bertoldo V, Montanari G, Zannoni L, Caprara G, Seracchioli R. Question mark form of uterus: a simple sonographic sign associated with the presence of adenomyosis. Ultrasound Obstet Gynecol. 2015;46(1):126–7. Xholli A, Scovazzi U, Londero AP, Evangelisti G, Cavalli E, Schiaffino MG, et al. Angle of uterine flexion and adenomyosis. J Clin Med. 2022;11(11):3214. Zhu J, Liu S, Gao D. Application of color Doppler ultrasound in microscopic imaging diagnosis of adenomyosis. Scanning. 2022;2022:2366871. Habiba M, Benagiano G. Classifying adenomyosis: progress and challenges. Int J Environ Res Public Health. 2021;18(23):12386. Gracia M, de Guirior C, Valdés-Bango M, Rius M, Ros C, Matas I, Tortajada M, et al. Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery. Sci Rep. 2022;12(1):7086. Bazot M, Cortez A, Darai E, Rouger JE, Chopier J, Antoine J-M, et al. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Hum Reprod. 2001;16:2427–33. Sun YL, Wang CB, Lee CY, Wun TH, Lin P, Lin YH, et al. Transvaginal sonographic criteria for the diagnosis of adenomyosis based on histopathologic correlation. Taiwan J Obstet Gynecol. 2010;49(1):40–4. Neal S, Morin S, Werner M, Gueye NA, Pirtea P, Patounakis G, et al. Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study. Ultrasound Obstet Gynecol. 2020;56(4):611–7. Levgur M, Abadi MA, Tucker A. Adenomyosis: symptoms, histology, and pregnancy terminations. Obstet Gynecol. 2000;95(5):688–91. Sammour A, Pirwany I, Usubutun A, Arseneau J, Tulandi T. Correlations between extent and spread of adenomyosis and clinical symptoms. Gynecol Obstet Investig. 2002;54(4):213–6. Pinzauti S, Lazzeri L, Tosti C, Centini G, Orlandini C, Luisi S, et al. Transvaginal sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis: association with symptoms. Ultrasound Obstet Gynecol. 2015;46(6):730–6. Naftalin J, Hoo W, Nunes N, Holland T, Mavrelos D, Jurkovic D. Association between ultrasound features of adenomyosis and severity of menstrual pain. Ultrasound Obstet Gynecol. 2016;47:779–83. Imanaka S, Shigetomi H, Kawahara N, Kobayashi H. Clinicopathological characteristics and imaging findings to identify adenomyosis-related symptoms. Reprod Med Biol. 2021;20(4):435–43. Kobayashi H, Matsubara S, Imanaka S. Clinicopathological features of different subtypes in adenomyosis: focus on early lesions. PLoS One. 2021;16(7):e0254147. Exacoustos C, Lazzeri L, Martire FG, Russo C, Martone S, Centini G, et al. Ultrasound findings of adenomyosis in adolescents: type and grade of the disease. J Minim Invasive Gynecol. 2022;29(2):291–299.e1. Exacoustos C, Morosetti G, Conway F, Camilli S, Martire FG, Lazzeri L, et al. New sonographic classification of adenomyosis: do type and degree of adenomyosis correlate to severity of symptoms? J Minim Invasive Gynecol. 2020;27(6):1308–15. Pistofidis G, Makrakis E, Koukoura O, Bardis N, Balinakos P, Anaf V. Distinct types of uterine adenomyosis based on laparoscopic and histopathologic criteria. Clin Exp Obstet Gynecol. 2014;41(2):113–8. Naftalin J, Hoo W, Pateman K, Mavrelos D, Foo X, Jurkovic D. Is adenomyosis associated with menorrhagia? Hum Reprod. 2014;29:473–9. Turner BM, Cramer SF, Heller DS. The pathogenesis of abnormal uterine bleeding in myopathic uteri. Ann Diagn Pathol. 2021;52:151726. Iwasawa T, Takahashi T, Maeda E, Ishiyama K, Takahashi S, Suganuma R, et al. Effects of localisation of uterine adenomyosis on outcome of in vitro fertilisation/intracytoplasmic sperm injection fresh and frozen-thawed embryo transfer cycles: a multicentre retrospective cohort study. Reprod Biol Endocrinol. 2021;19(1):84. Stanekova V, Woodman RJ, Tremellen K. The rate of euploid miscarriage is increased in the setting of adenomyosis. Hum Reprod Open. 2018;2018(3):hoy011. Cozzolino M, Tartaglia S, Pellegrini L, Troiano G, Rizzo G, Petraglia F. The effect of uterine adenomyosis on IVF outcomes: a systematic review and meta-analysis. Reprod Sci. 2022;29(11):3177–93. Mavrelos D, Holland TK, O’Donovan O, Khalil M, Ploumpidis G, Jurkovic D, et al. The impact of adenomyosis on the outcome of IVF-embryo transfer. Reprod BioMed Online. 2017;35:549–54. Yan L, Ding L, Tang R, Chen ZJ. Effect of adenomyosis on in vitro fertilization/intracytoplasmic sperm injection outcomes in infertile women: a retrospective cohort study. Gynecol Obstet Investig. 2014;77(1):14–8. Bourdon M, Santulli P, Oliveira J, Marcellin L, Maignien C, Melka L, et al. Focal adenomyosis is associated with primary infertility. Fertil Steril. 2020;114(6):1271–7. Marques ALS, Andres MP, Mattos LA, Gonçalves MO, Baracat EC, Abrão MS. Association of 2D and 3D transvaginal ultrasound findings with adenomyosis in symptomatic women of reproductive age: a prospective study. Clinics (Sao Paulo). 2021;76:e2981. Benaglia L, Cardellicchio L, Leonardi M, Faulisi S, Vercellini P, Paffoni A, et al. Asymptomatic adenomyosis and embryo implantation in IVF cycles. Reprod BioMed Online. 2014;29(5):606–11. Dueholm M, Lundorf E, Sørensen JS, Ledertoug S, Olesen F, Laursen H. Reproducibility of evaluation of the uterus by transvaginal sonography, hysterosonographic examination, hysteroscopy and magnetic resonance imaging. Hum Reprod. 2002;17(1):195–200. Author information Authors and Affiliations Contributions Conception and design: H. K. Acquisition of data: H. K. and S. I. Analysis and interpretation of data: H. K. and S. I. Writing the manuscript: H. K. and S. I. The final version of the manuscript has been read and approved by the authors: H. K. and S. I. Corresponding author Ethics declarations Ethics Approval and Consent to Participate Not applicable. Patient Consent for Publication Not applicable. Competing Interests The authors declare no competing interests. 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