Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery

Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery Meritxell Gracia, Cristian de Guirior, Marta Valdés-Bango, Mariona Rius, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-893239/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Deep endometriosis (DE) occurs in 15–30% of patients with endometriosis and is associated with concomitant adenomyosis in around 49% of cases. There are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications. Thus, the aim of the present study was to evaluate the impact of adenomyosis on surgical complications in women with deep endometriosis undergoing laparoscopic surgery. Methods A retrospective cohort study including women referred to the endometriosis unit of a referral teaching hospital. Two expert sonographers preoperatively diagnosed DE and adenomyosis. DE was defined according to the criteria of the International Deep Endometriosis Analysis group. Adenomyosis was considered when 3 or more ultrasound criteria of the Morphological Uterus Sonographic Assessment group were present. Demographical variables, current medical treatment, symptoms, DE location, surgical time, hospital stay and difference in pre and post hemoglobin levels were collected. The Clavien-Dindo classification was used to assess surgical complications, and multivariate analysis was performed to compare patients with and without adenomyosis. Results 157 DE patients were included into the study; 77 (49.05%) had adenomyosis according to transvaginal ultrasound (TVS) and were classified in the A group, and 80 (50.95%) had no adenomyosis and were classified in the noA group. Adenomyosis was associated with a higher rate of surgical complications: 33.76% (A group) vs. 12.5% (noA group) (p < 0.001). Multivariate analysis showed a 4.56-fold increased risk of presenting complications in women with adenomyosis (CI: 1.9–11.3; p = 0.001) independently of undergoing hysterectomy. There was a statistically significant association between the number of criteria of adenomyosis present in each patient and the proportion of patients presenting surgical complications (p < 0.001). Conclusions Adenomyosis increases the risk of presenting complications in DE surgery after controlling for demographic, clinical and surgical factors and should be considered an independent preoperative risk factor of surgical complications. Surgery Endocrinology & Metabolism Clavien-Dindo laparoscopy complications outcome surgery adenomyosis Figures Figure 1 Introduction For years endometriosis and adenomyosis were related, but they are now mainly considered as separate entities [ 1 , 2 ]. Deep endometriosis (DE) occurs in 15–30% of patients with endometriosis and is associated with concomitant adenomyosis in around 49% of cases [ 3 , 4 ]. Advances in pelvic ultrasound provide a high accuracy in the diagnosis of the different forms of endometriosis [ 5 , 6 ] and adenomyosis [ 7 – 9 ] and allow topographical planning prior to surgery [ 10 , 11 ]. Hormone therapy is the first line treatment for DE and adenomyosis in patients not seeking pregnancy. When severe pain persists following medical treatment, or in cases of intestinal or ureteral obstruction, conservative or radical surgical approaches may be necessary depending on the need for fertility preservation [ 12 , 13 ]. Surgery has been widely demonstrated to improve endometriosis-related symptoms [ 14 ]. However, resection of endometriotic lesions is often challenging. Most of DE interventions are highly complex and are associated with a significant risk of complications that must be preoperatively taken into account [ 15 ]. Moreover, there is no a reliable preoperative marker to determine the severity of endometriosis for extrapolation to surgical difficulty [ 16 ]. To the best of our knowledge, there are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications. Thus, the aim of the present study was to assess the impact of adenomyosis on the presentation of surgical complications in patients with DE undergoing laparoscopic surgery. Materials And Methods A retrospective cohort study including women referred to the Endometriosis Unit of the Hospital Clinic of Barcelona, who underwent DE surgery from July 2018 to December 2019 was designed. The study was approved by the Ethical Committee of the Hospital Clinic (Reg: HCB/2019/1152), all research was performed in accordance with relevant guidelines and regulations and informed consent was obtained from all patients. A preoperative diagnosis of DE and adenomyosis was made by two experts sonographers within 6 months prior to surgery. DE was described according to the fourth step method suggested by the International Deep Endometriosis Analysis (IDEA) group [ 6 ] with a 2-dimensional and 3-dimensional transvaginal sonography (TVS) using an endovaginal probe (type RIC5-9, Voluson V730 Expert; GE Healthcare, Milwaukee, WI) with previous bowel preparation [ 5 ]. The location and extent of DE was described within the pelvis: rectovaginal septum, torus uterinus, uterosacral ligaments, vaginal fornix, bladder, ureteral and bowel involvement. Adenomyosis ultrasound features according to the criteria of the Morphological Uterus Sonographic Assessment (MUSA) group [ 7 ], were: asymmetrical thickening, cysts, hyperechoic islands, fan-shaped shadowing, echogenic subendometrial lines and buds, translesional vascularity, irregular junctional zone and interrupted junctional zone. Adenomyosis was diagnosed when at least 3 of the above-mentioned ultrasound features were present according to our hospital protocol. DE surgery was always performed by the same team of skilled endometriosis surgeons and a colorectal surgeon or urologist when needed. In order to standardize all the surgical procedures, they were classified into: adnexal (including salpingectomy, ovarian cystectomy or CO2 laser vaporization and adnexectomy), pelvic (vagina, uterosacral ligaments, torus uterinus and rectovaginal septum), bowel (shaving, discoid or segmental resection), urinary (ureterolysis, bladder nodule excision, nephrectomy) and hysterectomy. Some patients underwent more than one of these procedures. In addition, endometriosis was staged according to the revised-American Society of Reproductive Medicine (r-ASRM) classification score [ 17 ]. The following demographic data were collected: age, body mass index (BMI), previous endometriosis surgery, infertility, parity, preoperative hormonal treatment and surgical indication. The endometriosis-related symptoms considered were: dysmenorrhea, dyspareunia, dyschezia, dysuria and non-cyclic pelvic pain, using a numerical rating scale (NRS) in which 0 was no pain and 10 unbearable pain. Abnormal uterine bleeding (AUB) was also registered. Patients were divided into two groups according to the preoperative TVS features: with adenomyosis (A) or without adenomyosis (noA). The main goal of the study was to compare postoperative complications in the two groups according to the Clavien-Dindo (CD) classification [ 18 ]. Differences in demographic characteristics, medical treatment, symptoms, DE location, types of DE surgery, surgical time (minutes), hospital stay (days) and pre and post hemoglobin levels (gr/dl) were also assessed. Statistical analysis Statistical analysis was performed using SPSS v 21.0 software (IBM, Armonk, NY, USA). Patient characteristics were described using frequency tables for nominal variables and measures of central tendency and dispersion for continuous variables. To compare outcomes between the two groups, the Chi-squared or Fisher exact tests was used for categorical data, and continuous variables were compared using independent t-tests or the Mann-Whitney test as appropriate. Bivariate logistic regression analysis was used to determine the factors related to the incidence of surgical complications. All bivariate statistical tests were performed at a significance level of p < 0.05 (two-sided). Independent variables that were related to complications in the bivariate analysis with a p < 0.15 were candidates for inclusion in the multivariate logistic regression model. This model explained the probability of the presentation of surgical complications with respect to non-presentation of complications as a function of the variables included. For the multivariate analysis, up to p < 0.10 was illustrated. Furthermore, we also conducted a subanalysis of the complications between groups considering patients without hysterectomy. Results A total of 157 patients undergoing DE surgery were included during the study period. According to TVS, 77 (49.05%) patients had 3 or more adenomyosis criteria and were classified in the A group and 80 (50.95%) patients had less than 3 adenomyosis criteria and were classified in the noA group. No differences were observed between groups regarding age, BMI and parity ( Table 1 ) . A total of 52.86 % of women had one or more previous endometriosis surgeries, with no significant differences between groups. Among the 157 patients studied, 130 (82.81%) received preoperative continuous hormonal medical treatment, mainly with oral combined contraceptives, with no significant differences between groups. Table 1 Demographic characteristics and endometriosis-related symptoms ADENOMYOSIS (A) N = 77 NO ADENOMYOSIS (noA) N = 80 P Value Age, years (mean ± SD) 38.22 ± 6.63 37.64 ± 5.85 NS BMI kg/m 2 (mean ± SD) 24.45 ± 4.98 23.90 ± 5.41 NS Parity (mean ± SD) 0.43 ± 0.81 0.41 ± 0.83 NS Infertility 36 (46.75) 28 (35) NS Hormonal treatment n (%): None Combined contraceptives Progestins LNG-IUD aGnRH 14 (18.18) 32 (41.55) 13 (16.88) 5 (6.49) 13 (16.88) 13 (16.25) 36 (45) 13 (16.25) 3 (3.75) 15 (18.75) NS DE location n (%): Torus uterinus Vaginal fornix Uterosacral ligaments Rectovaginal septum Ureteral + bladder Bowel Ovarian endometrioma 49 (63) 16 (20.77) 44 (57.14) 5 (6.49) 14 (18.18) 35 (45.45) 60 (77.9) 27 (33.75) 10 (12.5) 32 (40) 6 (7.5) 12 (15) 32 (40) 52 (65) NS Previous endometriosis surgery n (%): None 1 procedure ≥ 2 procedures 33 (42.85) 34 (44.15) 10 (12.98) 41 (51.25) 33 (41.25) 6 (7.5) NS AUB n (%): No Yes 48 (62.33) 29 (37.66) 51 (63.75) 29 (36.25) NS Dysmenorrhea* (mean ± SD) 7.20 ± 3.13 6.85 ± 3.03 NS Dyspareunia (mean ± SD) 4.72 ± 4.05 4.61 ± 3.84 NS Dyschezia (mean ± SD) 3.60 ± 3.87 3.88 ± 3.88 NS Non-cyclic pelvic pain (mean ± SD) 4.69 ± 3.50 4.09 ± 3.49 NS Dysuria (mean ± SD) 1.22 ± 2.81 1.02 ± 2.41 NS Data are given as n or %. Symptoms are expressed with Numeric Rating Scale (NRS). LNG-IUD: Levonorgestrel Intra Uterine Device; aGnRH: analog-Gonadotropin-releasing Hormone; SD: standard deviation; n: number; %: percentage; AUB: Abnormal Uterine Bleeding; NS: non-significant; BMI: body mass index *Dysmenorrhea NRS was reported in patients with regular monthly periods: 14 patients in A group (18.18%) and 13 in noA Group (16.25%) Table 1 shows the endometriosis-related symptoms of both study groups. The mean of all NRS scores and the presence of AUB, although not significant, were higher (except for dyschezia) in the group of patients with adenomyosis (group A). The main indication for surgery was pain in both groups (96%) despite receiving medical treatment, with 46.75% (group A) and 35% (group no A) having associated infertility (p 0.495). The different interventions performed in the two groups are shown in Table 2 . All the procedures were performed by laparoscopy with 56 hysterectomies being registered: 38 in the A group and 18 in the noA group (p 0.002). DE was confirmed histologically in all cases as well as the presence of adenomyosis when hysterectomy or uterus-sparing adenomyosis surgery was performed. Table 2 Surgical procedures and r-ASRM classification ADENOMYOSIS (A) N = 77 NO ADENOMYOSIS (noA) N = 80 P Value Type of surgery n (%): Adnexal surgery *: Pelvic DE + : Bowel Surgery: • Shaving • Segmental resection Urinary Surgery: • Bladder nodule excision • Ureterolysis/reimplantation Hysterectomy: 56/157 (35.66) 72 (93.5) 55 (71.42) 22 (28.57) 13 (16.88) 5 (6.49) 9 (11.68) 38 (49.35) 67 (83.75) 45 (56.25) 19 (23.75) 13 (16.25) 6 (7.5) 6 (7.5) 18 (22.5) NS NS NS NS NS NS .002 r-ASRM score n (%): I II III IV 3 (3.89) 4 (5.19) 12 (15.58) 58 (75.32) 1 (1.25) 9 (11.25) 19 (23.75) 51 (63.75) NS * Adnexal surgery: unilateral or bilateral including ovarian endometriomas, salpingectomy, adnexectomy. + Pelvic DE: including vagina, uterosacral ligaments, torus uterinus. Data are given as n or %. r-ASRM score: revised-American Society of Reproductive Medicine; SD: standard deviation; n: number; %: percentage; NS: non-significant The presence of adenomyosis showed significant differences in the CD complications rates: A group 33.76%, noA group 12.5% (p 0.001), mean surgical time: A group 231 ± 101 minutes, noA group 181.08 ± 91.61 minutes (p 0.011) and difference in pre-post hemoglobin levels: A group 2.17 ± 1.89 gr/dl, and noA group 2.05 ± 1.22 gr/dl (p 0,049). There were no significant differences in length of hospital stay: A group 3.32 ± 3.7 days, noA group 2.75 ± 1.85 days (p 0.09). Most of the complications were minor (88.8% CD I and II) ( Table 3 ). Four patients in the A group, presented major complications (CD III): one rectovaginal fistula, two anastomotic leakages and one bowel obstruction. All patients were recovered at 3–6 months of post-operative follow-up. Table 3 Surgical data and complications ADENOMYOSIS (A) N = 77 NO ADENOMYOSIS (noA) N = 80 P Value Surgical time minutes (mean ± SD) 231 ± 101 181.08 ± 91.61 .011 Difference pre-post Hemoglobin levels g/dl (mean ± SD) 2.17 ± 1.89 2.05 ± 1.22 .049 Hospital Stay days (mean ± SD) 3.32 ± 3.7 2.75 ± 1.85 .09 CD Complications n (%) I II III IV 26 (33.76) 12 (15.58) 10 (12.98) 4 (5.19) 0 (0) 10 (12.5) 4 (5) 6 (7.5) 0 (0) 0 (0) .001 Data are given as n or %. SD: standard deviation; CD: Clavien-Dindo; n: number; %:percentage Multiple logistic regression showed the following factors to be independently related to the development of surgical complications: adenomyosis, surgical time, bowel resection and hysterectomy. The attributed risk of each factor is shown in Table 4 . The risk of presenting complications increased 4.56 times in the A group (CI: 1.9–11.3; p = 0.001). Moreover, there was a statistically significant association between the number of criteria of adenomyosis and the proportion of patients presenting a surgical complication (p < 0.001) ( Fig. 1 ). Table 4 Risk factors related to surgical complications: multivariate logistic regression analysis Odds Ratio 95% CI P Value Adenomyosis 4.558 1.845–11.26 .001 Surgical time 1.010 1.004–1.016 .002 Bowel resection 2.558 0.843–7.761 .097 Hysterectomy 3.110 1.293–7.478 .011 CI: confidential interval A higher CD complication rate was also observed in the A group when excluding patients with hysterectomy in both groups ( Table 5 ). Table 5 Surgical data considering patients without hysterectomy ADENOMYOSIS (A) N = 39 NO ADENOMYOSIS (noA) N = 62 P Value Surgical time minutes (mean ± SD) 226.1 ± 105.7 185.52 ± 81.35 .032 Difference pre-post Hemoglobin levels g/dl (mean ± SD) 2.22 ± 1.41 1.85 ± 1.11 .175 Hospital Stay days (mean ± SD) 3.85 ± 4.59 2.58 ± 1.76 .02 CD Complications n (%) I II III IV 13 (33.33) 7(17.94) 5(12.82) 1 (2.56) 0 (0) 5 (8) 3 (4.83) 2 (3.22) 0 (0) 0 (0) .003 Data are given as n or %. SD: standard deviation; CD: Clavien-Dindo; n: number; %:percentage Discussion The possibility of identifying predictable preoperative features that could modify surgical results would be of great interest [ 19 ]. The results of our study suggest that the presence of adenomyosis increases the surgical complication rate in DE patients. Furthermore, this increased risk is related to the number of TVS adenomyosis criteria. While the impact of adenomyosis on surgical results has been assessed in other benign conditions, to our knowledge no previous study has evaluated the impact of adenomyosis on surgical complications in women with DE undergoing laparoscopic surgery [ 20 ]. Previous studies in benign pathology reported an increased rate of bladder and ureteral complications for vaginal hysterectomy in patients with only adenomyosis [ 21 ] but this was not observed with the laparoscopic approach [ 22 ]. Accurate preoperative imaging assessment has been described in cases of bowel DE, and several previous studies have reported a high accuracy of up to 89.9% and 98.1% in correlating TVS findings with surgical difficulties [ 11 , 16 ]. These studies are primarily based on ultrasound findings of ovarian mobility and the presence or not of bowel endometriosis but did not specifically included the presence of adenomyosis. Due to the surgical complexity of DE procedures, even in expert hands, the rate of complications is still considerable especially when colorectal resection is involved, ranging from 3.4–25% [ 19 , 23 , 24 ]. In our study, clinically relevant complications (CD type III) were only recorded in 2.54% of cases. These complications were also related to bowel surgeries, similar to previously published data [ 13 , 23 – 25 ]. Hysterectomy is considered the surgical treatment of choice for most women with adenomyosis who do not wish to preserve fertility after medical treatment has failed [ 26 ]. Concomitant hysterectomy in the A group was performed in 49.35% vs. 22.5% in the noA group (p 0.002). Hysterectomy in the context of DE has been shown to be associated to longer operative time [ 27 ]. The application of a multivariate model demonstrated that hysterectomy was an independent factor with or without adenomyosis. This was also confirmed in the subanalysis of surgical outcomes between groups performed, considering only patients without hysterectomy. In addition, all the factors that may contribute to a higher risk of complications (bowel and urinary surgery, previous endometriosis surgeries and operative time) were adjusted in the multivariate analysis in order to prevent bias. On the other hand, Van den Bosch et al. [ 8 ] proposed a new classification system which includes different adenomyosis subtypes, including intrinsic/extrinsic adenomyosis, adenomyosis externa and focal adenomyosis in the outer myometrium (FAOM) [ 3 , 28 ]. Focal adenomyosis commonly affects the external part of the myometrium and may attach the uterus to other structures, hindering surgery and increasing the risk of presenting surgical complications and impairing other surgical outcomes and may be a possible explanation for our study results although a definite reason is unknown. Moreover, the chronic inflammation, proliferation and fibrosis that supports the pathogenesis of adenomyosis [ 1 ] may be another feasible explanation, creating an inflammatory environment more likely to present an increased risk of surgical complications. Further prospective studies are needed to support this correlation with the type of adenomyosis (since this classification was published after performing the present study) and to find a pathogenic mechanism explaining the clinical presentation of our surgical results. This study has several strengths: it is the first to describe the impact of adenomyosis on surgical outcomes by conditioning the presentation of a surgical complication. Second, the TVS evaluation was performed by two expert sonographers who have previously demonstrated a high diagnostic TVS accuracy for determining the presence of DE (sensitivity 100%, specificity 96%) [ 5 ]. Moreover, all surgeries were performed by the same team of experienced surgeons in advanced laparoscopy surgery focused on endometriosis. However, some limitations need to be acknowledged. This was a retrospective, single-center study. In the absence of previous studies, no formal power calculation was performed for sample size determination. Secondly, a patient selection bias may be present. The patients were probably more complex since they were referred to the Endometriosis Unit of a tertiary university center and were, therefore, associated with a higher degree of surgical difficulty and may not be comparable with the general population. Conclusion According to our findings, adenomyosis is an independent preoperative risk factor for surgical complications after adjustment for known demographic, clinical and surgical risk factors. Thus, patients with a preoperative diagnosis of DE and adenomyosis programmed to undergo surgery should be informed about the possible development of surgical complications and ideally attended in a referral center by an expert multidisciplinary endometriosis team. However, further prospective studies should be carried out in order to confirm these findings taking into account different adenomyosis phenotypes. References Vannuccini, S. et al. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online [Internet] , 35 (5), 592–601 (2017). Maruyama, S., Imanaka, S., Nagayasu, M., Kimura, M. & Kobayashi, H. Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease? Eur J Obstet Gynecol Reprod Biol , 253 , 191–197 (2020). Chapron, C. et al. Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod , 32 (7), 1393–1401 (2017). Lazzeri, L. et al. 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Drs Meritxell Gracia , Cristian de Guirior , Marta Valdés - Bango , Mariona Rius , Cristina Ros , Isabel Matas , Marta Tortajada , María Ángeles Martínez - Zamora , Lara Quintas and Francisco Carmona have no conflicts of interest or financial ties to disclose . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 05 Jan, 2022 Reviews received at journal 15 Nov, 2021 Reviewers agreed at journal 10 Nov, 2021 Reviewers invited by journal 10 Nov, 2021 Editor assigned by journal 10 Nov, 2021 Editor invited by journal 13 Sep, 2021 Submission checks completed at journal 13 Sep, 2021 First submitted to journal 10 Sep, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Barcelona","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"Ángeles","lastName":"Martínez-Zamora","suffix":""},{"id":51724063,"identity":"caa3f8cb-cdbb-4b87-95ce-13d7070f76cb","order_by":8,"name":"Lara Quintas","email":"","orcid":"","institution":"Hospital Clínic de Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Lara","middleName":"","lastName":"Quintas","suffix":""},{"id":51724064,"identity":"afb6544e-70de-4c58-ad39-13ae5cd75205","order_by":9,"name":"Francisco Carmona","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBAC9gYog5+BueEAgwERWngOQBmSDYwwLcxEajE4wAizkJAW9sPPPt2ouCNvfPxg4+GCAjsG/vbzB/Br4Ukznp1z5pnhtjOJDYdnGCQzSJxJxm+LvQSDMXNu22HGbTcYGw7zGIC8Q0ALjwT7Z5AW+80zYFr4HxPSwgO2JXGDBEyLBCFbeHKKmXPOHE6eAfILj0Eyj8SNx/hjh4f9+GbmnIrDtv3thw9/5vljJ8ffn/gAvzUYZpCmfBSMglEwCkYBVgAAqOlDibf2dAcAAAAASUVORK5CYII=","orcid":"","institution":"Hospital Clínic de Barcelona","correspondingAuthor":true,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Carmona","suffix":""}],"badges":[],"createdAt":"2021-09-10 13:59:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-893239/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-893239/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13404538,"identity":"4f445ac2-46f6-4f0a-bf2f-1119dc74332b","added_by":"auto","created_at":"2021-09-15 14:20:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16056,"visible":true,"origin":"","legend":"Association between adenomyosis criteria and surgical complications.","description":"","filename":"FIGURE1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-893239/v1/7fb03116ef866c156aff7bf8.jpg"},{"id":13714888,"identity":"4afe3d41-5e6a-4f4e-af38-f13a1aa33c99","added_by":"auto","created_at":"2021-09-17 14:40:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":390705,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-893239/v1/fac0103a-abda-4903-9ffb-371332c2875e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFor years endometriosis and adenomyosis were related, but they are now mainly considered as separate entities [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Deep endometriosis (DE) occurs in 15\u0026ndash;30% of patients with endometriosis and is associated with concomitant adenomyosis in around 49% of cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdvances in pelvic ultrasound provide a high accuracy in the diagnosis of the different forms of endometriosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and adenomyosis [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and allow topographical planning prior to surgery [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHormone therapy is the first line treatment for DE and adenomyosis in patients not seeking pregnancy. When severe pain persists following medical treatment, or in cases of intestinal or ureteral obstruction, conservative or radical surgical approaches may be necessary depending on the need for fertility preservation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Surgery has been widely demonstrated to improve endometriosis-related symptoms [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, resection of endometriotic lesions is often challenging. Most of DE interventions are highly complex and are associated with a significant risk of complications that must be preoperatively taken into account [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Moreover, there is no a reliable preoperative marker to determine the severity of endometriosis for extrapolation to surgical difficulty [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. To the best of our knowledge, there are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications.\u003c/p\u003e \u003cp\u003eThus, the aim of the present study was to assess the impact of adenomyosis on the presentation of surgical complications in patients with DE undergoing laparoscopic surgery.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eA retrospective cohort study including women referred to the Endometriosis Unit of the Hospital Clinic of Barcelona, who underwent DE surgery from July 2018 to December 2019 was designed.\u003c/p\u003e \u003cp\u003e The study was approved by the Ethical Committee of the Hospital Clinic (Reg: HCB/2019/1152), all research was performed in accordance with relevant guidelines and regulations and informed consent was obtained from all patients.\u003c/p\u003e \u003cp\u003eA preoperative diagnosis of DE and adenomyosis was made by two experts sonographers within 6 months prior to surgery. DE was described according to the fourth step method suggested by the International Deep Endometriosis Analysis (IDEA) group [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] with a 2-dimensional and 3-dimensional transvaginal sonography (TVS) using an endovaginal probe (type RIC5-9, Voluson V730 Expert; GE Healthcare, Milwaukee, WI) with previous bowel preparation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The location and extent of DE was described within the pelvis: rectovaginal septum, torus uterinus, uterosacral ligaments, vaginal fornix, bladder, ureteral and bowel involvement. Adenomyosis ultrasound features according to the criteria of the Morphological Uterus Sonographic Assessment (MUSA) group [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], were: asymmetrical thickening, cysts, hyperechoic islands, fan-shaped shadowing, echogenic subendometrial lines and buds, translesional vascularity, irregular junctional zone and interrupted junctional zone. Adenomyosis was diagnosed when at least 3 of the above-mentioned ultrasound features were present according to our hospital protocol.\u003c/p\u003e \u003cp\u003eDE surgery was always performed by the same team of skilled endometriosis surgeons and a colorectal surgeon or urologist when needed. In order to standardize all the surgical procedures, they were classified into: adnexal (including salpingectomy, ovarian cystectomy or CO2 laser vaporization and adnexectomy), pelvic (vagina, uterosacral ligaments, torus uterinus and rectovaginal septum), bowel (shaving, discoid or segmental resection), urinary (ureterolysis, bladder nodule excision, nephrectomy) and hysterectomy. Some patients underwent more than one of these procedures. In addition, endometriosis was staged according to the revised-American Society of Reproductive Medicine (r-ASRM) classification score [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe following demographic data were collected: age, body mass index (BMI), previous endometriosis surgery, infertility, parity, preoperative hormonal treatment and surgical indication. The endometriosis-related symptoms considered were: dysmenorrhea, dyspareunia, dyschezia, dysuria and non-cyclic pelvic pain, using a numerical rating scale (NRS) in which 0 was no pain and 10 unbearable pain. Abnormal uterine bleeding (AUB) was also registered.\u003c/p\u003e \u003cp\u003ePatients were divided into two groups according to the preoperative TVS features: with adenomyosis (A) or without adenomyosis (noA). The main goal of the study was to compare postoperative complications in the two groups according to the Clavien-Dindo (CD) classification [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Differences in demographic characteristics, medical treatment, symptoms, DE location, types of DE surgery, surgical time (minutes), hospital stay (days) and pre and post hemoglobin levels (gr/dl) were also assessed.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS v 21.0 software (IBM, Armonk, NY, USA). Patient characteristics were described using frequency tables for nominal variables and measures of central tendency and dispersion for continuous variables.\u003c/p\u003e \u003cp\u003eTo compare outcomes between the two groups, the Chi-squared or Fisher exact tests was used for categorical data, and continuous variables were compared using independent t-tests or the Mann-Whitney test as appropriate. Bivariate logistic regression analysis was used to determine the factors related to the incidence of surgical complications. All bivariate statistical tests were performed at a significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (two-sided). Independent variables that were related to complications in the bivariate analysis with a p\u0026thinsp;\u0026lt;\u0026thinsp;0.15 were candidates for inclusion in the multivariate logistic regression model. This model explained the probability of the presentation of surgical complications with respect to non-presentation of complications as a function of the variables included. For the multivariate analysis, up to p\u0026thinsp;\u0026lt;\u0026thinsp;0.10 was illustrated.\u003c/p\u003e \u003cp\u003eFurthermore, we also conducted a subanalysis of the complications between groups considering patients without hysterectomy.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 157 patients undergoing DE surgery were included during the study period. According to TVS, 77 (49.05%) patients had 3 or more adenomyosis criteria and were classified in the A group and 80 (50.95%) patients had less than 3 adenomyosis criteria and were classified in the noA group.\u003c/p\u003e \u003cp\u003eNo differences were observed between groups regarding age, BMI and parity \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. A total of 52.86 % of women had one or more previous endometriosis surgeries, with no significant differences between groups. Among the 157 patients studied, 130 (82.81%) received preoperative continuous hormonal medical treatment, mainly with oral combined contraceptives, with no significant differences between groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics and endometriosis-related symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADENOMYOSIS\u003c/p\u003e \u003cp\u003e(A) N\u0026thinsp;=\u0026thinsp;77\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNO ADENOMYOSIS (noA) N\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.22\u0026thinsp;\u0026plusmn;\u0026thinsp;6.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI kg/m\u003csup\u003e2\u003c/sup\u003e (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.90\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (46.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHormonal treatment n (%):\u003c/p\u003e \u003cp\u003eNone\u003c/p\u003e \u003cp\u003eCombined contraceptives\u003c/p\u003e \u003cp\u003eProgestins\u003c/p\u003e \u003cp\u003eLNG-IUD\u003c/p\u003e \u003cp\u003eaGnRH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (18.18)\u003c/p\u003e \u003cp\u003e32 (41.55)\u003c/p\u003e \u003cp\u003e13 (16.88)\u003c/p\u003e \u003cp\u003e5 (6.49)\u003c/p\u003e \u003cp\u003e13 (16.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (16.25)\u003c/p\u003e \u003cp\u003e36 (45)\u003c/p\u003e \u003cp\u003e13 (16.25)\u003c/p\u003e \u003cp\u003e3 (3.75)\u003c/p\u003e \u003cp\u003e15 (18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDE location n (%):\u003c/p\u003e \u003cp\u003eTorus uterinus\u003c/p\u003e \u003cp\u003eVaginal fornix\u003c/p\u003e \u003cp\u003eUterosacral ligaments\u003c/p\u003e \u003cp\u003eRectovaginal septum\u003c/p\u003e \u003cp\u003eUreteral\u0026thinsp;+\u0026thinsp;bladder\u003c/p\u003e \u003cp\u003eBowel\u003c/p\u003e \u003cp\u003eOvarian endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (63)\u003c/p\u003e \u003cp\u003e16 (20.77)\u003c/p\u003e \u003cp\u003e44 (57.14)\u003c/p\u003e \u003cp\u003e5 (6.49)\u003c/p\u003e \u003cp\u003e14 (18.18)\u003c/p\u003e \u003cp\u003e35 (45.45)\u003c/p\u003e \u003cp\u003e60 (77.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (33.75)\u003c/p\u003e \u003cp\u003e10 (12.5)\u003c/p\u003e \u003cp\u003e32 (40)\u003c/p\u003e \u003cp\u003e6 (7.5)\u003c/p\u003e \u003cp\u003e12 (15)\u003c/p\u003e \u003cp\u003e32 (40)\u003c/p\u003e \u003cp\u003e52 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious endometriosis surgery n (%):\u003c/p\u003e \u003cp\u003eNone\u003c/p\u003e \u003cp\u003e1 procedure\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2 procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (42.85)\u003c/p\u003e \u003cp\u003e34 (44.15)\u003c/p\u003e \u003cp\u003e10 (12.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (51.25)\u003c/p\u003e \u003cp\u003e33 (41.25)\u003c/p\u003e \u003cp\u003e6 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAUB n (%):\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (62.33)\u003c/p\u003e \u003cp\u003e29 (37.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (63.75)\u003c/p\u003e \u003cp\u003e29 (36.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysmenorrhea* (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.20\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.85\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspareunia (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.72\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;4.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.61\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyschezia\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.60\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.88\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-cyclic pelvic pain (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.69\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.09\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysuria (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are given as n or %. Symptoms are expressed with Numeric Rating Scale (NRS). LNG-IUD: Levonorgestrel Intra Uterine Device; aGnRH: analog-Gonadotropin-releasing Hormone; SD: standard deviation; n: number; %: percentage; AUB: Abnormal Uterine Bleeding; NS: non-significant; BMI: body mass index\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Dysmenorrhea NRS was reported in patients with regular monthly periods: 14 patients in A group (18.18%) and 13 in noA Group (16.25%)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the endometriosis-related symptoms of both study groups. The mean of all NRS scores and the presence of AUB, although not significant, were higher (except for dyschezia) in the group of patients with adenomyosis (group A). The main indication for surgery was pain in both groups (96%) despite receiving medical treatment, with 46.75% (group A) and 35% (group no A) having associated infertility (p 0.495).\u003c/p\u003e \u003cp\u003eThe different interventions performed in the two groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. All the procedures were performed by laparoscopy with 56 hysterectomies being registered: 38 in the A group and 18 in the noA group (p 0.002). DE was confirmed histologically in all cases as well as the presence of adenomyosis when hysterectomy or uterus-sparing adenomyosis surgery was performed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical procedures and r-ASRM classification\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADENOMYOSIS\u003c/p\u003e \u003cp\u003e(A) N\u0026thinsp;=\u0026thinsp;77\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNO ADENOMYOSIS (noA) N\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery n (%):\u003c/p\u003e \u003cp\u003eAdnexal surgery *:\u003c/p\u003e \u003cp\u003ePelvic DE \u003csup\u003e+\u003c/sup\u003e:\u003c/p\u003e \u003cp\u003eBowel Surgery:\u003c/p\u003e \u003cp\u003e\u0026bull; Shaving\u003c/p\u003e \u003cp\u003e\u0026bull; Segmental resection\u003c/p\u003e \u003cp\u003eUrinary Surgery:\u003c/p\u003e \u003cp\u003e\u0026bull; Bladder nodule excision\u003c/p\u003e \u003cp\u003e\u0026bull; Ureterolysis/reimplantation\u003c/p\u003e \u003cp\u003eHysterectomy: 56/157 (35.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (93.5)\u003c/p\u003e \u003cp\u003e55 (71.42)\u003c/p\u003e \u003cp\u003e22 (28.57)\u003c/p\u003e \u003cp\u003e13 (16.88)\u003c/p\u003e \u003cp\u003e5 (6.49)\u003c/p\u003e \u003cp\u003e9 (11.68)\u003c/p\u003e \u003cp\u003e38 (49.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (83.75)\u003c/p\u003e \u003cp\u003e45 (56.25)\u003c/p\u003e \u003cp\u003e19 (23.75)\u003c/p\u003e \u003cp\u003e13 (16.25)\u003c/p\u003e \u003cp\u003e6 (7.5)\u003c/p\u003e \u003cp\u003e6 (7.5)\u003c/p\u003e \u003cp\u003e18 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003eNS\u003c/p\u003e \u003cp\u003e\u003cb\u003e.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003er-ASRM score n (%):\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.89)\u003c/p\u003e \u003cp\u003e4 (5.19)\u003c/p\u003e \u003cp\u003e12 (15.58)\u003c/p\u003e \u003cp\u003e58 (75.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.25)\u003c/p\u003e \u003cp\u003e9 (11.25)\u003c/p\u003e \u003cp\u003e19 (23.75)\u003c/p\u003e \u003cp\u003e51 (63.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e*\u003c/b\u003e Adnexal surgery: unilateral or bilateral including ovarian endometriomas, salpingectomy, adnexectomy. \u003csup\u003e+\u003c/sup\u003e Pelvic DE: including vagina, uterosacral ligaments, torus uterinus.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are given as n or %. r-ASRM score: revised-American Society of Reproductive Medicine; SD: standard deviation; n: number; %: percentage; NS: non-significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe presence of adenomyosis showed significant differences in the CD complications rates: A group 33.76%, noA group 12.5% (p 0.001), mean surgical time: A group 231\u0026thinsp;\u0026plusmn;\u0026thinsp;101 minutes, noA group 181.08\u0026thinsp;\u0026plusmn;\u0026thinsp;91.61 minutes (p 0.011) and difference in pre-post hemoglobin levels: A group 2.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89 gr/dl, and noA group 2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22 gr/dl (p 0,049). There were no significant differences in length of hospital stay: A group 3.32\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 days, noA group 2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85 days (p 0.09). Most of the complications were minor (88.8% CD I and II) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Four patients in the A group, presented major complications (CD III): one rectovaginal fistula, two anastomotic leakages and one bowel obstruction. All patients were recovered at 3\u0026ndash;6 months of post-operative follow-up.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical data and complications\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADENOMYOSIS (A) N\u0026thinsp;=\u0026thinsp;77\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNO ADENOMYOSIS (noA) N\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical time minutes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e231\u0026thinsp;\u0026plusmn;\u0026thinsp;101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e181.08\u0026thinsp;\u0026plusmn;\u0026thinsp;91.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifference pre-post Hemoglobin levels g/dl (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital Stay days (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.32\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD Complications\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (33.76)\u003c/p\u003e \u003cp\u003e12 (15.58)\u003c/p\u003e \u003cp\u003e10 (12.98)\u003c/p\u003e \u003cp\u003e4 (5.19)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (12.5)\u003c/p\u003e \u003cp\u003e4 (5)\u003c/p\u003e \u003cp\u003e6 (7.5)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are given as n or %. SD: standard deviation; CD: Clavien-Dindo; n: number; %:percentage\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMultiple logistic regression showed the following factors to be independently related to the development of surgical complications: adenomyosis, surgical time, bowel resection and hysterectomy. The attributed risk of each factor is shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The risk of presenting complications increased 4.56 times in the A group (CI: 1.9\u0026ndash;11.3; p\u0026thinsp;=\u0026thinsp;0.001). Moreover, there was a statistically significant association between the number of criteria of adenomyosis and the proportion of patients presenting a surgical complication (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors related to surgical complications: multivariate logistic regression analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdenomyosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4.558\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.845\u0026ndash;11.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical time\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e1.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.004\u0026ndash;1.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBowel resection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2.558\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.843\u0026ndash;7.761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHysterectomy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3.110\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.293\u0026ndash;7.478\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCI: confidential interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA higher CD complication rate was also observed in the A group when excluding patients with hysterectomy in both groups \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical data considering patients without hysterectomy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADENOMYOSIS (A) N\u0026thinsp;=\u0026thinsp;39\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNO ADENOMYOSIS (noA) N\u0026thinsp;=\u0026thinsp;62\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical time minutes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e226.1\u0026thinsp;\u0026plusmn;\u0026thinsp;105.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e185.52\u0026thinsp;\u0026plusmn;\u0026thinsp;81.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifference pre-post Hemoglobin levels g/dl (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital Stay days (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD Complications\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (33.33)\u003c/p\u003e \u003cp\u003e7(17.94)\u003c/p\u003e \u003cp\u003e5(12.82)\u003c/p\u003e \u003cp\u003e1 (2.56)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8)\u003c/p\u003e \u003cp\u003e3 (4.83)\u003c/p\u003e \u003cp\u003e2 (3.22)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are given as n or %. SD: standard deviation; CD: Clavien-Dindo; n: number; %:percentage\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe possibility of identifying predictable preoperative features that could modify surgical results would be of great interest [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The results of our study suggest that the presence of adenomyosis increases the surgical complication rate in DE patients. Furthermore, this increased risk is related to the number of TVS adenomyosis criteria.\u003c/p\u003e \u003cp\u003eWhile the impact of adenomyosis on surgical results has been assessed in other benign conditions, to our knowledge no previous study has evaluated the impact of adenomyosis on surgical complications in women with DE undergoing laparoscopic surgery [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Previous studies in benign pathology reported an increased rate of bladder and ureteral complications for vaginal hysterectomy in patients with only adenomyosis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] but this was not observed with the laparoscopic approach [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Accurate preoperative imaging assessment has been described in cases of bowel DE, and several previous studies have reported a high accuracy of up to 89.9% and 98.1% in correlating TVS findings with surgical difficulties [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These studies are primarily based on ultrasound findings of ovarian mobility and the presence or not of bowel endometriosis but did not specifically included the presence of adenomyosis.\u003c/p\u003e \u003cp\u003eDue to the surgical complexity of DE procedures, even in expert hands, the rate of complications is still considerable especially when colorectal resection is involved, ranging from 3.4\u0026ndash;25% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In our study, clinically relevant complications (CD type III) were only recorded in 2.54% of cases. These complications were also related to bowel surgeries, similar to previously published data [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHysterectomy is considered the surgical treatment of choice for most women with adenomyosis who do not wish to preserve fertility after medical treatment has failed [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Concomitant hysterectomy in the A group was performed in 49.35% vs. 22.5% in the noA group (p 0.002). Hysterectomy in the context of DE has been shown to be associated to longer operative time [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The application of a multivariate model demonstrated that hysterectomy was an independent factor with or without adenomyosis. This was also confirmed in the subanalysis of surgical outcomes between groups performed, considering only patients without hysterectomy.\u003c/p\u003e \u003cp\u003eIn addition, all the factors that may contribute to a higher risk of complications (bowel and urinary surgery, previous endometriosis surgeries and operative time) were adjusted in the multivariate analysis in order to prevent bias.\u003c/p\u003e \u003cp\u003eOn the other hand, Van den Bosch et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] proposed a new classification system which includes different adenomyosis subtypes, including intrinsic/extrinsic adenomyosis, adenomyosis externa and focal adenomyosis in the outer myometrium (FAOM) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Focal adenomyosis commonly affects the external part of the myometrium and may attach the uterus to other structures, hindering surgery and increasing the risk of presenting surgical complications and impairing other surgical outcomes and may be a possible explanation for our study results although a definite reason is unknown. Moreover, the chronic inflammation, proliferation and fibrosis that supports the pathogenesis of adenomyosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] may be another feasible explanation, creating an inflammatory environment more likely to present an increased risk of surgical complications. Further prospective studies are needed to support this correlation with the type of adenomyosis (since this classification was published after performing the present study) and to find a pathogenic mechanism explaining the clinical presentation of our surgical results.\u003c/p\u003e \u003cp\u003eThis study has several strengths: it is the first to describe the impact of adenomyosis on surgical outcomes by conditioning the presentation of a surgical complication. Second, the TVS evaluation was performed by two expert sonographers who have previously demonstrated a high diagnostic TVS accuracy for determining the presence of DE (sensitivity 100%, specificity 96%) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, all surgeries were performed by the same team of experienced surgeons in advanced laparoscopy surgery focused on endometriosis.\u003c/p\u003e \u003cp\u003eHowever, some limitations need to be acknowledged. This was a retrospective, single-center study. In the absence of previous studies, no formal power calculation was performed for sample size determination. Secondly, a patient selection bias may be present. The patients were probably more complex since they were referred to the Endometriosis Unit of a tertiary university center and were, therefore, associated with a higher degree of surgical difficulty and may not be comparable with the general population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAccording to our findings, adenomyosis is an independent preoperative risk factor for surgical complications after adjustment for known demographic, clinical and surgical risk factors. Thus, patients with a preoperative diagnosis of DE and adenomyosis programmed to undergo surgery should be informed about the possible development of surgical complications and ideally attended in a referral center by an expert multidisciplinary endometriosis team. However, further prospective studies should be carried out in order to confirm these findings taking into account different adenomyosis phenotypes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVannuccini, S. \u003cem\u003eet al.\u003c/em\u003e Pathogenesis of adenomyosis: an update on molecular mechanisms. \u003cem\u003eReprod Biomed Online [Internet]\u003c/em\u003e, \u003cb\u003e35\u003c/b\u003e (5), 592\u0026ndash;601 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaruyama, S., Imanaka, S., Nagayasu, M., Kimura, M. \u0026amp; Kobayashi, H. Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease? \u003cem\u003eEur J Obstet Gynecol Reprod Biol\u003c/em\u003e, \u003cb\u003e253\u003c/b\u003e, 191\u0026ndash;197 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChapron, C. \u003cem\u003eet al.\u003c/em\u003e Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. \u003cem\u003eHum Reprod\u003c/em\u003e, \u003cb\u003e32\u003c/b\u003e (7), 1393\u0026ndash;1401 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLazzeri, L. \u003cem\u003eet al.\u003c/em\u003e Preoperative and postoperative clinical and transvaginal ultrasound findings of adenomyosis in patients with deep infiltrating endometriosis. \u003cem\u003eReprod Sci\u003c/em\u003e, \u003cb\u003e21\u003c/b\u003e (8), 1027\u0026ndash;1033 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRos, C. \u003cem\u003eet al.\u003c/em\u003e Bowel Preparation Improves the Accuracy of Transvaginal Ultrasound in the Diagnosis of Rectosigmoid Deep Infiltrating Endometriosis: A Prospective Study. \u003cem\u003eJ Minim Invasive Gynecol\u003c/em\u003e, \u003cb\u003e24\u003c/b\u003e (7), 1145\u0026ndash;1151 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerriero, S. \u003cem\u003eet al.\u003c/em\u003e 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 Sep 1;48(3):318\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Den Bosch, T. \u003cem\u003eet al.\u003c/em\u003e Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: A consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. 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Rethinking mechanisms, diagnosis and management of endometriosis. \u003cem\u003eNat Rev Endocrinol\u003c/em\u003e, \u003cb\u003e15\u003c/b\u003e (11), 666\u0026ndash;682 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeckstein, J. \u003cem\u003eet al.\u003c/em\u003e Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. \u003cem\u003eHum Reprod Open\u003c/em\u003e, \u003cb\u003e2020\u003c/b\u003e (1), 1\u0026ndash;25 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTompsett, J. \u003cem\u003eet al.\u003c/em\u003e Ultrasound-Based Endometriosis Staging System: Validation Study to Predict Complexity of Laparoscopic Surgery. \u003cem\u003eJ Minim Invasive Gynecol\u003c/em\u003e, \u003cb\u003e26\u003c/b\u003e (3), 477\u0026ndash;483 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRevised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997 May;67(5):817 \u0026ndash; 21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindo, D., Demartines, N. \u0026amp; Clavien, P. A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. \u003cem\u003eAnn Surg\u003c/em\u003e, \u003cb\u003e240\u003c/b\u003e (2), 205\u0026ndash;213 (2004 Aug).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbr\u0026atilde;o, M. S., Andres, M. P., Barbosa, R. N., Bassi, M. A. \u0026amp; Kho, R. M. Optimizing Perioperative Outcomes with Selective Bowel Resection Following an Algorithm Based on Preoperative Imaging for Bowel Endometriosis. \u003cem\u003eJ Minim Invasive Gynecol\u003c/em\u003e, \u003cb\u003e27\u003c/b\u003e (4), 883\u0026ndash;891 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStruble, J., Reid, S., Bedaiwy, M. A. \u0026amp; Adenomyosis A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol [Internet] 2016;23(2):164\u0026ndash;85. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.jmig.2015.09.018\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFuruhashi, M., Miyabe, Y., Katsumata, Y., Oda, H. \u0026amp; Imai, N. Comparison of complications of vaginal hysterectomy in patients with leiomyomas and in patients with adenomyosis. \u003cem\u003eArch Gynecol Obstet\u003c/em\u003e, \u003cb\u003e262\u003c/b\u003e (1\u0026ndash;2), 69\u0026ndash;73 (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeikle, S. F., Nugent, E. W. \u0026amp; Orleans, M. 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O. \u003cem\u003eet al.\u003c/em\u003e Persistence of Symptoms After Total vs Supracervical Hysterectomy in Women with Histopathological Diagnosis of Adenomyosis. \u003cem\u003eJ Minim Invasive Gynecol\u003c/em\u003e, \u003cb\u003e26\u003c/b\u003e (5), 891\u0026ndash;896 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUccella, S. \u003cem\u003eet al.\u003c/em\u003e Impact of endometriosis on surgical outcomes and complications of total laparoscopic hysterectomy. \u003cem\u003eArch Gynecol Obstet\u003c/em\u003e, \u003cb\u003e294\u003c/b\u003e (4), 771\u0026ndash;778 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo, S. W. The Pathogenesis of Adenomyosis vis-\u0026agrave;-vis Endometriosis. \u003cem\u003eJ Clin Med\u003c/em\u003e, \u003cb\u003e9\u003c/b\u003e (2), 485 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrs \u003cb\u003eMeritxell Gracia\u003c/b\u003e, \u003cb\u003eCristian de Guirior\u003c/b\u003e, \u003cb\u003eMarta Vald\u0026eacute;s\u003c/b\u003e-\u003cb\u003eBango\u003c/b\u003e, \u003cb\u003eMariona Rius\u003c/b\u003e, \u003cb\u003eCristina Ros\u003c/b\u003e, \u003cb\u003eIsabel Matas\u003c/b\u003e, \u003cb\u003eMarta Tortajada\u003c/b\u003e, \u003cb\u003eMar\u0026iacute;a \u0026Aacute;ngeles Mart\u0026iacute;nez\u003c/b\u003e-\u003cb\u003eZamora\u003c/b\u003e, \u003cb\u003eLara Quintas and Francisco Carmona have no conflicts of interest or financial ties to disclose\u003c/b\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Clavien-Dindo, laparoscopy, complications, outcome, surgery, adenomyosis","lastPublishedDoi":"10.21203/rs.3.rs-893239/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-893239/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDeep endometriosis (DE) occurs in 15\u0026ndash;30% of patients with endometriosis and is associated with concomitant adenomyosis in around 49% of cases. There are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications. Thus, the aim of the present study was to evaluate the impact of adenomyosis on surgical complications in women with deep endometriosis undergoing laparoscopic surgery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study including women referred to the endometriosis unit of a referral teaching hospital. Two expert sonographers preoperatively diagnosed DE and adenomyosis. DE was defined according to the criteria of the International Deep Endometriosis Analysis group. Adenomyosis was considered when 3 or more ultrasound criteria of the Morphological Uterus Sonographic Assessment group were present. Demographical variables, current medical treatment, symptoms, DE location, surgical time, hospital stay and difference in pre and post hemoglobin levels were collected. The Clavien-Dindo classification was used to assess surgical complications, and multivariate analysis was performed to compare patients with and without adenomyosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e157 DE patients were included into the study; 77 (49.05%) had adenomyosis according to transvaginal ultrasound (TVS) and were classified in the A group, and 80 (50.95%) had no adenomyosis and were classified in the noA group. Adenomyosis was associated with a higher rate of surgical complications: 33.76% (A group) vs. 12.5% (noA group) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate analysis showed a 4.56-fold increased risk of presenting complications in women with adenomyosis (CI: 1.9\u0026ndash;11.3; p\u0026thinsp;=\u0026thinsp;0.001) independently of undergoing hysterectomy. There was a statistically significant association between the number of criteria of adenomyosis present in each patient and the proportion of patients presenting surgical complications (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAdenomyosis increases the risk of presenting complications in DE surgery after controlling for demographic, clinical and surgical factors and should be considered an independent preoperative risk factor of surgical complications.\u003c/p\u003e","manuscriptTitle":"Adenomyosis is an independent risk factor for complications in deep endometriosis laparoscopic surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-15 14:20:47","doi":"10.21203/rs.3.rs-893239/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-01-05T16:35:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-11-15T15:20:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78a60429-df39-4ea2-9cff-d5fcf0b4d145","date":"2021-11-10T06:52:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-11-10T06:42:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-11-10T06:19:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-09-13T17:46:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-09-13T17:43:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-09-10T13:53:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"af3916f8-d37b-44f1-a65f-adb3b16da8ab","owner":[],"postedDate":"September 15th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":7201685,"name":"Surgery"},{"id":7201686,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2022-03-28T11:44:12+00:00","versionOfRecord":[],"versionCreatedAt":"2021-09-15 14:20:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-893239","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-893239","identity":"rs-893239","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}