{"paper_id":"88919499-0558-45b4-a588-ca234c7033ec","body_text":"7\nGuidelines for diagnosis and treatment of endometriosis\nMauro Busacca1, Massimo Candiani2, Vito Chiàntera3, Maria Elisabetta Coccia4, Cristofaro De \nStefano5, Alessandra Di Giovanni 6, Caterina Exacoustos 7, Stefano Guerriero 8, Lucia Lazzeri 9, \nStefano Luisi 9, Mario Malzoni 6, Salvo Micalef 10, Fabio Parazzini 11, Valentino Remorgida 12, \nRenato Seracchioli13, Flavia Sorbi4, Michele Vignali1, Errico Zupi7, Felice Petraglia4 (Cohordinator) \n1 Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano\n2 Dipartimento di Ginecologia e Ostetricia, IRCCS San Raffaele, Milano\n3 Università  degli Studi di Palermo, Palermo\n4 Dipartimento di Scienze Biomediche, Sperimentali e Cliniche Mario Serio, Università degli Studi di  \n  Firenze, Firenze\n5 Ospedale Civile Avellino, Avellino\n6 Endoscopica Malzoni, Center  for Advanced  Endoscopic Pelvic Surgery,  Avellino\n7 Dipartimento of Biomedicina and Prevenzione Clinica ostetrico e Ginecologica, Università di Roma “Tor \n  Vergata”, Roma\n8 Dipartimento di Scienze Chirurgiche. Università degli Studi di Cagliari\n9 Ostetrica e Ginecologica, Dipartimento di Medicina Molecolare e dello Sviluppo, Università di Siena,  \n  Siena\n10 Ospedale S. Anna, Torino\n11 Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano\n12 IRCCS San Martino IST Università di Genova, Genova\n13 Ginecologia e Fisiopatologia della Riproduzione Umana, Università di Bologna, Bologna\nTABLE OF CONTENTS\nAUTHORS\nRECIPIENTS\nMETHODS\nRECOMMENDATIONS\nBACKGROUND\nSECTION 1: OVARIAN ENDOMETRIOSIS\n1.1 Diagnosis \n1.1.1 Role of ultrasound\n1.1.2 Diagnostic Criteria \n1.2 Medical Therapy \n1.2.1 Medical therapy vs surgery\nCorresponding Author: Dr. Felice Petraglia\nfelice.petraglia@unifi.it\nCopyright 2018, Partner-Graf srl, Prato\nDOI: 10.14660/2385-0868-85\nGyn ae c o l o g y  &  Obstetrics\nItalian Journal of\nJune 2018 - Vol. 30 - N. 2 - Quarterly - ISSN 2385 - 0868\nFONDAZIONE\nCONFALONIERI\nRAGONESE\n1.2.2 Medical therapy to lower the risk of recurrence  \n of ovarian lesion after surgery\n1.2.3 Medical therapy in the control of pain\n1.2.4 Medical therapy in adolescents \n1.3 Surgical Therapy\n1.3.1 Role of surgical therapy in the treatment of   \n endometrioma\n1.3.2 Surgical modalities in the treatment of   \n endometrioma.\n1.3.3 Effect of surgery on ovarian reserve\n1.4 Approach to the infertile patient\n1.4.1 Endometrioma as cause of infertility\n1.4.2 Surgical treatment before ART\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n8\nSECTION 2: PERITONEAL  ENDOMETRIOSIS\n2.1 Diagnosis\n2.1.1 Role of ultrasound and other imaging   \n techniques\n2.1.2 Sonographic Diagnostic Criteria for   \n peritoneal/superficial endometriosis\n2.1.3 Sonographic Diagnostic Criteria for tubal   \n endometriosis\n2.1.4 Ultrasound evaluation in case of pelvic   \n endometriosis infiltrating\n2.2 Medical Therapy \n2.2.1 Medical therapy in the prevention and   \n therapy of pain syndrome\n2.3 Surgical Therapy\n2.3.1 The aims of surgical treatment \n2.3.2 Surgical technique\n2.4 Approach to the infertile patient\n2.4.1 Superficial and deep endometriosis as a cause  \n of infertility\n2.4.2 Surgical treatment before ART\nSECTION 3: ENDOMETRIOSIS IN ATYPICAL \nSITES\n3.1 Endometriosis of the abdominal wall,   \n inguinal canal, umbilicus\n3.2 Endometriosis in other sites\n3.2.1 Bowel deep endometriosis\n3.2.2 Bladder endometriosis\n3.3 Medical Therapy\n3.3.1 Medical therapy in different location\n3.4 Surgical Therapy\n3.4.1 Surgical therapy in different location\nAUTHORS\nThese Recommendations have been written \nby a group of medical professionals (Drafters) \nidentified by SIGO, AOGOI and AGUI Scientific \nCommittees with the organizational support of \nthe Confalonieri-Ragonese Foundation.\nRECIPIENTS\nThese Recommendations are addressed to all \nprofessionals who deal with the diagnosis and \ntreatment of the diseases covered by these \nguidelines.\nMETHODS\nWriting medical Recommendations is a complex \nactivity in terms of methods, and requires \nadvanced technical skills, resources and time \nthat companies usually are not able to provide. \nThese recommendations are based on systematic \nreviews.\nToday, however, acquiring the critical skills \nrequired to assess the extent to which systematic \nreviews (or already existing Guidelines/\nrecommendations produced in Italy or in other \ncountries) are sufficiently valid from a scientific \npoint of view to be taken into account for their \napplication in Italy is the priority, and not\nwriting new systematic reviews.\nBased on these considerations, the production of \nthese Recommendations included the following\noperational phases:\n• Identification of expert drafters\n• Identification of systematic reviews and the \nmost recent guidelines published on the topic\n• Formulation of clinical themes used to \ndevelop the guidelines\n• Definition of recommendations by individual \ndrafters through their response to the \nidentified clinical themes\n• Definition of the recommendations grading \nby the group of expert drafters\nSpecifically, the Quality Level and the strength \nof these recommendations were graded and \nexpressed in Roman numerals (I to VI) and in \nletters (A to E). The Quality Level refers to the \nlikelihood that a certain amount of knowledge \nderives from studies planned and conducted \nin such a way as to produce valid information \nwithout systematic errors, while the Strength of \nGuidelines for diagnosis and treatment of endometriosis\n\n9\nRecommendation refers to the likelihood that the \npractical application of a recommendation will \nlead to an improvement in the health status of the \ntarget population to which the recommendation \nis addressed.\nThe Level of Quality and Strength of \nRecommendations were defined according to the \ncriteria suggested by the Methodological Manual \nof the National Guidelines System ( table 1).\nTo develop these phases, an operational meeting \nwas organised during the SIGO-AOGOI AGUI \nNational Congress, followed by an exchange of \nmaterial and comments via email.\nThe Recommendations approved by a majority \nof the Group of Drafters have been revised by \nthe Auditors appointed by the three Scientific \nCommittees.\nBACKGROUND\nIn recent years, several scientific societies have \nproduced consensus guidelines/documents \nor recommendations for the treatment of \nendometriosis. In Italy, guidelines were produced \nfor the treatment of pelvic endometriosis in \nthe late ‘90, using the Delphi’ method  by the \ncollaborative Group of Italian Endometriosis \nStudy Group (GISE). Many recommendations/\nguidelines published are similar to each other \nand without any special changes over the years, \nan aspect that indicates the shortage of high-\nquality and innovative recent studies. However, \nthe therapeutic scenario has in part changed in \nrecent years, also following the introduction of \nnew therapeutic diagnostic methodologies or \nmolecules. \nObjective of this document is to provide Italian \ngynecologists a useful tool in clinical practice, \nbased on updated evidences. \nSECTION 1:\nOVARIAN ENDOMETRIOSIS\n1.1 Diagnosis \n1.1.1 Role of ultrasound\nTransvaginal ultrasound (TV) should be the \nfirst diagnostic approach in case of ovarian \nendometriosis. The diagnostic accuracy of \ntransvaginal ultrasonography for the diagnosis \nof ovarian endometriosis is very high.\n1.1.2 Diagnostic Criteria \nA “typical” endometrioma usually appears at \nultrasound as a unilocular or, less frequently \nmultilocular (with a low number of locules) cyst, \nwith a homogeneous low-level echogenicity \n(ground glass) of the fluid content and regular \nwalls with poor vascularization  (1,2).\nSome endometriomas can contain scarcely \nvascularized internal septa or can present as a \nfluid-dense cysts with an internal hyperechogenic \nlevel and a poor pericystic vascular pattern. \nColor/power Doppler analysis of endometriotic \ncysts is useful in the differential diagnosis with \nother histotypes of adnexal masses  (2,3).\nEndometriomas with atypical appearance may \npresent hyperechogenic internal content due \nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\nTable 1. \nQuality level and Strength of the Recommendations - Grading.\nFrom: ISS-PNLG 2002\nQUALITY LEVEL\nI Evidence obtained from multiple randomised controlled \ntrials and/or systematic reviews of randomised trials\nII Evidence obtained from a single randomised study of \nadequate design\nIII Evidence obtained from non-randomised cohort studies \nwith concurrent or historical controls or their meta-analysis\nIV Evidence obtained from retrospective case-control studies or \ntheir meta-analyses\nV Evidence obtained from case studies («case series») without \na control group\nVI Evidence based on the opinion of authoritative experts \nor expert committees as indicated in the guidelines or \nconsensus conferences, or based on the opinions of the \nmembers of the working group responsible for these \nguidelines\nSTRENGTH OF THE RECOMMENDATION\nA The execution of that particular procedure or diagnostic \ntest is strongly recommended. It indicates a particular \nrecommendation supported by good quality scientific \nevidence, even if not necessarily type I or II\nB There are doubts about whether that particular procedure or \nsurgery should always be recommended, but it is believed \nthat its execution should be carefully taken into account\nC There is substantial uncertainty in favour of or against the \nrecommendation to perform the procedure or surgery\nD The execution of the procedure is not recommended\nE The execution of the procedure is strongly discouraged\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n10\nto blood clots or fibrin deposits lying adjacent \nto the cyst wall. Such content will show no \nvascularisation at Doppler examination.\nOvarian endometriosis is frequently associated \nwith pelvic adhesions and deep infiltrating lesions. \nThe percentage of this association varies from 20 \nto 80%. When both ovaries present adhesions  \nthey may tend to prolapse in the pouch of \nDouglas and adhere posteriorly to the uterine wall  \nshowing the typical so-called “kissing ovaries” \nultrasonographic sign, possibly associated with \nconcomitant posterior infiltrating endometriosis \n(20%) and tubal involvement (90%) (4). \nA detailed ultrasonographic evaluation of pelvic \nadhesions, deep pelvic lesions and adenomyosis \nis of outmost importance in patients with ovarian \nendometriosis (5). \nThe sonographic appearance of endometriomas \nmay vary depending on the hormonal status of \nthe patient. Post-menopausal endometriomas \nmore frequently appear as solid or multilocular-\nsolid cysts with anechoic fluid content or with \nmixed echogenicity fluid content, sometimes \nmimicking borderline or  malignant neoplasia  (6).\nThe ultrasound pattern of endometriomas may \ntransform also during pregnancy. In pregnant \npatients the typical endometrioma can undergo \na decidualization process and appear as a \nunilocular- or multilocular-solid cyst, due to the \npresence of internal papillae, with a regular and \nsmooth surface and often vascularized at Power \nDoppler examination.  In these cases, knowledge \nof  the presence of the endometrioma before \npregnancy can facilitate a correct diagnosis and \nminimize the risk of unnecessary surgery  (7). \nBorderline and malignant tumors arising from \nendometriomas are rare (more often endometrial \nor clear call trimas): in these cases they show \ntypical sonographic features of non-benign \nadnexal pathology such as cysts with vasularized \ninternal papillar or solid tissue. Patients with \nan endometrioma that also present associated \nrisk factors (e.s. familiar hystory of malignancy, \nmenopause, infertility,  long term persistent \ncysts) should undergo careful US follow-up with \nsurgical removal and histologic evaluation when \nsuspicious findings arise (8).\n1) Timmerman D, Valentin L, Bourne TH, Collins WP, \nVerrelst H, Vergote I, International Ovarian Tumor \nAnalysis G. Terms, definitions and measurements to \ndescribe the sonographic features of adnexal tumors: \na consensus opinion from the International Ovarian \nTumor Analysis (IOTA) Group . Ultrasound Obstet \nGynecol 2000; 16: 500–505.\n2) Exacoustos C, Manganaro L, Zupi E. Imaging for the \nevaluation of endometriosis and adenomyosis . Best \nPract Res Clin Obstet Gynaecol. 2014;28:655-81. \n3) Van Holsbeke C, Van Calster B, Guerriero S, Savelli \nL, Paladini D, Lissi AA, Czekierdowski A, Fischerova \nD, Zhang J, Mestdagh G et al. Endometriomas: their \nultrasound characteristics. Ultrasound Obstet Gynecol \n2010;35:730–740.\n4) Ghezzi F, Raio L, Cromi A, Duwe DG, Beretta \nP, Buttarelli M, MuellerMD. ‘‘Kissing ovaries’’: a \nsonographic sign of moderate to severe endometriosis. \nFertil Steril 2005; 83: 143–147.\n5) Exacoustos C, Malzoni M, Di Giovanni A, Lazzeri \nL, Tosti C, Petraglia F, Zupi E. Ultrasound mapping \nsystem for the surgical management of deep \ninfiltrating endometriosis . Fertil Steril. 2014;102:143-\n150.\n6) Guerriero S, Van Calster B, Somigliana E, Ajossa \nS, Froyman W, De Cock B, Coosemans A, Fischerová \nD, Van Holsbeke C, Alcazar JL, Testa AC, Valentin L, \nBourne T, Timmerman D. Age-related differences in \nthe sonographic characteristics of endometriomas . \nHum Reprod. 2016;31:1723-31. \n7) Mascilini F,Moruzzi C, Giansiracusa C, Guastafierro \nF, Savelli L, De Meis L, Epstein E, Timor-Tritsch IE, \nMailath-Pokorny M, Ercoli A, Exacoustos C, Benacerraf \nBR, Valentin L, Testa AC. Imaging in gynecological \ndisease. Clinical and ultrasound characteristics of \ndecidualized endometriomas surgically removed \nduring pregnancy . Ultrasound Obstet Gynecol 2014; \n44: 354–60.\n8) Nezhat FR, Apostol R, Nezhat C, Pejovic T. New \ninsights in the pathophysiology of ovarian cancer \nand implications  for screening and prevention . Am J \nObstet Gynecol 2015; 213):262-7.\n \n1.2 Medical Therapy \nThe objectives of medical therapy in case of \novarian lesion are:\n• treatment of the ovarian lesion before or \ninstead of  surgery \n• reduction of   risk recurrence  after surgery\n• pain control\nGuidelines for diagnosis and treatment of endometriosis\n\n11\n1.2.1 Medical therapy vs surgery\nThe treatment of  endometrioma depends mainly \nby the symptoms and the patient’s desire of \npregnancy. Options include waiting, medical \nor surgical therapy, and assisted reproduction \ntechniques (ART).\nYap and Collaborators  (1)  in a review of the \nliterature considered the role of medical treatment \npre-and post-surgery  according to  cyst size, \npain and infertility. With regard to pre-operative \ntherapy, two studies were included: in both of \nthem there was a difference in the size of the \nendometrioma of 1-2 cm between the treated vs \nuntreated group, but there was no evidence of a \nclinical benefit of therapy.\nMuzii et al.  (2) , in a recent meta-analysis on the \nefficacy of  combined oral contraceptives (COC), \nadministered cyclically versus non-cyclically,  \nshowed no significant reduction in endometrioma \nbefore surgical treatment on post-operative \noutcome. The efficacy of progestins in ovarian \nendometriosis has been object of several studies (3-5). \nA randomized multicenter study evaluated the \nefficacy of administration of dienogest in 187 \nwomen, with a statistically significant reduction \nin the size of the cysts  (5). In consideration of side \neffects, therapy with GnRH agonists or with \ndanazol  (equally effective) should be considered \nas second-line treatment  (6-9) . Medical therapy is  \nsymptomatic and not cytoreductive  (10, 11).\nRecommendation Level of \nevidence\nStrength of \nrecommendation\nMedical treatment of ovarian \nendometriosis (endometrioma) can be \nconsidered in case of lesions of limited \nsize, but we have no data that allow us \nto consider such treatment as effective \nin the long period\nV B\nMedical treatment with progestins \nalone (IA) or with estrogens (IIIA) may \nbe considered in patients with pain \nand waiting for surgery with the goal \nof controlling pain but not of improve \nsurgical outcomes \nI A\n1) Yap C, Furness S, Farquhar. Pre and post-operative \nmedical therapy for endometriosis surgery . Cochrane \nDatabase Syst Rev. 2004:CD003678.\n2) Muzii L, Di Tucci C, Achilli C, Di Donato V, Musella \nA, Palaia I, Panici PB. Continuous versus cyclic oral \ncontraceptives after laparoscopic excision of ovarian \nendometriomas: a systematic review and metaanalysis. \nAm J Obstet Gynecol. 2016 Feb;214(2):203-11\n3) Andres Mde P1, Lopes LA, Baracat EC, Podgaec \nS. Dienogest in the treatment of endometriosis: \nsystematic review . Arch Gynecol Obstet. 2015 \nSep;292(3):523-9.\n4) Kohler G, Faustmann TA, Gerlinger C, Seitz C, Mueck \nAO (2010). A dose-ranging study to determine the \nefficacy and safety of 1, 2, and 4 mg of dienogest daily \nfor endometriosis. Int J Gynaecol Obstet 108(1):21–25\n5) Momoeda M, Taketani Y. A randomized, double-\nblind, multicenter, parallel, dose-response study \nof dienogest in patients with endometriosis . Jpn \nPharmacol Ther 2007;35:769-83 \n6) Vercellini P, Somigliana E, Vigano P, Abbiati A, \nBarbara G, Crosignani PG. Endometriosis: current \ntherapies and new pharmacological developments . \nDrugs 2009;69:649–75\n7) Crosignani PG, Luciano A, Ray A, Bergqvist \nA. Subcutaneous depot medroxyprogesterone \nacetate versus leuprolide acetate in the treatment \nof endometriosis-associated pain . Human Reprod \n2006;21:248–56.\n8) Surrey ES. Gonadotropin-releasing hormone \nagonist and add-back therapy: what do the data show? \nCurr Opin Obstet Gynecol 2010;22:283–8.\n9) Somigliana E, Vigano P, Barbara G, Vercellini P. \nTreatment of endometriosis related pain: options and \noutcomes. Front Biosci 2009;1:455–65\n10) Vercellini P, Viganò P, Somigliana E, Fedele L. \nEndometriosis: pathogenesis and treatment . Nat. Rev. \nEndocrinol 2014 May;10(5):261-75\n11) Johnson N. P., Hummelshoj L. World Endometriosis \nSociety Montpellier Consortium. Consensus on \ncurrent management of endometriosis . Hum. Reprod. \n28, 1552-1568 (2013)\n1.2.2 Medical therapy to lower  the risk of recurrence of  \novarian lesion after surgery\nThe risk of recurrence of the ovarian lesion \nafter surgery is about 10% per year for the first \nfive years  (1) .  In consideration of the  impact  of \nsurgery on the ovarian function, it is necessary \nto improve clinical strategies aimed to prevent \nrepeated  surgery, especially in young and not \nsearching pregnancy patients  (2,3).\nMedical therapy after surgery for endometriosis \nhas the objective of reducing the risk of long-term \nrelapses, defined as recurrence of symptomatology \nor lesion after 12/24 months after surgery.  \nThere is some evidence that post-surgical \ncombined oral contraceptive (COC) use  lower \nthe risk  of recurrences of ovarian endometriosis. \nIn a randomized controlled prospective study  \nwomen who underwent laparoscopic enucleation \nof endometrioma were allocated to: no treatment,  \ntreatment with low doses monophasic  COC \nfor 24 months in cyclic or continuous regimen. \nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n12\nThe 2-year  recurrence rate  was significantly \nlower in treated patients (cyclic regimen: 14.7%,  \ncontinuing regimen: 8.2%, no treatment 29%). In \ncases of recurrence in treated patients  with both \nregimens of administration, size and growth of \nthe lesions were significantly lower than among  \nthe untreated patients. There were no significant \ndifferences between the continuous and cyclic \nregimes (4).\nThe similar efficacy of cyclic and continuous \nregimen in the prevention of recurrence of \novarian endometriosis is confirmed by another \nrandomized prospective study, which reports, \nhowever, more side effects  among patients \ntreated with continuous regimen  (5).\nA controlled randomized study has analyzed \nthe COC’s efficacy in the prevention of relapses \nwith different progestin formulation. The \nthree regimens tested with different progestins \n(desogestrel, gestodene and dienogest), showed \nno significant difference (26.5%, 31.8%, 20.5%). \nThe recurrence rate of untreated patients \n(74.7%) was  significantly higher than in any \nCOC treatment group  (6).  Ota et al.  (7) showed in \na retrospective cohort study that the  recurrence \nrate is significantly lower in patients with ovarian \nendometriosis treated with dienogest for five \nyears after  surgery, than in untreated  patients  \n(69% vs. 4%; OR = 0.09; 95% CI = 0.03 – 0.26;  \nP < 0.0001) In this study anemia occurred in 4% \ndue to metrorrhagia directly after administration, \nmetrorrhagia including spotting was observed \nin 20% at 1 year and decreases in bone mineral \ndensity and depression were observed in 4 and \n2.6%, respectively, in the dienogest group: these \nconditions did not require treatment interruptions.\n1) Guo, S.W. Recurrence of endometriosis and its \ncontrol. Hum Reprod Update. 2009; 15: 441–461\n2) Busacca, M., Riparini, J., Somigliana, E. et al. \nPostsurgical ovarian failure after laparoscopic \nexcision of bilateral endometriomas . Am. J. Obstet. \nGynaecol. 2006; 195: 421–425\n3) Vercellini, P., Somigliana, E., Viganò, P., de Matteis, \nS., Barbara, G., and Fedele, L. The effect of second-line \nsurgery on reproductive performance of women with \nrecurrent endometriosis: a systematic review . Acta \nObstet Gynecol Scand. 2009; 88: 1074–1082\n4) Seracchioli R, Mabrouk M, Frascà C, Manuzzi L, \nMontanari G, Keramyda A, Venturoli S. Long-term \ncyclic and continuous oral contraceptive therapy and \nendometrioma recurrence: a randomized controlled \ntrial. Fertil Steril  2010 Jan;93(1):52-6\n5) Muzii L., Di Tucci C., Achilli C., Di Donato V., \nMusella A., Palaia I., Panici P.B. Continuous versus \ncyclic oral contraceptives after laparoscopic excision \nof ovarian endometriomas: a systematic review and \nmetaanalysis. Am J Obstet Gynecol. 2016; 214(2):203-11 \n6) Cucinella, G., Granese, R., Calagna, G., Svelato, A., \nSaitta, S., Tonni, G. et al. Oral contraceptives in the \nprevention of endometrioma recurrence: does the \ndifferent progestins used make a difference? . Arch \nGynecol Obstet. 2013; 288: 821–827\n7) Ota, Y., Andou, M., Yanai, S., Nakajima, S., Fukuda, \nM., Takano, M. et al. Long-term administration \nof dienogest reduces recurrence after excision of \nendometrioma. J Endomet Pelv Pain Disord. 2015; 7: \n63–67\n1.2.3 Medical therapy in the control of pain\nIn case of pain, medical therapy of patients with \novarian endometriosis is similar to that of patients \nwith  superficial or deep endometriosis. \nIn  presence of pain symptomatology,  progestins \nalone  or,  in particular in case  of  contraceptive \nneeds, in association with estrogen, should be \nconsidered as first choice treatment  (1).\nControlled randomized studies have compared \nthe use of GnRH agonists vs progestins alone or \nCOC in the treatment of  pain associated with \nendometriosis: a higher frequency of side effects \nin the GnRH group was reported. \nRegidor et al.  (2)  compared Linestrenolo with \nLeuprorelina: In the Linestrenolo group there \nwas a reduction of dysmenorrhoea in 50% of \npatients and chronic pelvic pain in 59% of cases \nafter 6 months of treatment, vs  85 and 69%. In the \nLeuprorelina group respectively.\nStrowitzki et al.  (3) compared the use of dienogest \nvs monthly Leuprorelina and showed a similar \nreduction in pain symptomatology in the two \ngroups and  greater tolerability of the Dienogest.\nGuzick et al.  (4)  compared a COC-based ethinyl \nestradiol-norestisterone (35 mg/1 mg per day) \nvs Leuprorelina 11.25 mg every 2 weeks and \nnorestisterone 5 mg day). In both groups a \nGuidelines for diagnosis and treatment of endometriosis\n\n13\nreduction in pain  was observed. \nSystematic reviews of controlled randomized \ntrials (5,6)  concluded that  GnRH treatments, \nCOC and  progestins are equally effective in the \ncontrol of pain associated with endometriosis. \nStudies have shown that dienogest (2 mg/day) \nis an effective (in comparison with placebo) \ntherapy for the control of pain  in patients with \nendometriosis. Desonorgestrel has shown similar \nresults as GnRH analogues in pelvic pain control \nand in all other endometriosis-related symptoms. \nThere are no studies  comparing desonorgestrel \nwith other progestin or oestrogens formulations \nas a first-line therapy in the control of pain \nsymptomatology associated with endometriosis.\n1) Vercellini P., Buggio L., Berlanda N., Barbara G., \nSomigliana E., Bosari S. Estrogen-progestins and \nprogestins for the management of endometriosis . \nFertil Steril 2016 Dec; 106 (7):1552-1571. \n2) Regidor PA., Regidor M., Schmidt M., et al. \nProspective randomized study comparing the \nGnRH-agonist leuprorelin acetate and the gestagen \nlynestrenol in the treatment of severe endometriosis . \nGynecol Endocrinol 2001;15:202-9. \n3) Strowitzki T., Marr J., Gerlinger C. et al. Dienogest \nis as effective as leuprolide acetate in treating the \npainful symptoms of endometriosis; a 24-week, \nrandomized, multicentre, open-label trial . Hum \nReprod 2010;25:633-41.\n4) Guzick DS., Huang LS., Broadman BA., et al. \nRandomized trial of leuprolide versus continuous \noral contraceptive in the treatment of endometriosis-\nassociated pelvic pain. Fertil Steril 2011;95:1568-73.\n5) Jeng CJ., Chuang L., Shen J. A comparison of \nprogestogens or oral contraceptives and gonadotropin-\nreleasing hormone agonists for the treatment of \nendometriosis: a systematic review . Expert Opinion \non Pharmacotherapy, 2014; 15: 767-73.\n6) Andres M., Lopes L., Baracat E., Podgaec S. Dienogest \nin the treatment of endometriosis: systematic review . \nArch Gynecol Obstet 2015. 292:523-529. \n1.2.4  Medical therapy in adolescents \nLacking specific data  guidelines for adult women \nshould be considered.\n COC (cyclic or continuous use) associated \nwith non-steroidal anti-inflammatory drugs are \nindicated as first line treatment.\nIf the first-line therapies do not work,  taking \ninto account age and side effects, all the therapies \navailable for endometriosis in adults can be used \nin adolescents as  second-line therapies.\nClinicians should use GnRH-agonists  cautiously, \nsince teenagers may not have reached the \nmaximum bone density (1).\n1) Lee DY, Kim HJ, Yoon BK, Choi D. Clinical \ncharacteristics of adolescent endometrioma . J Pediatr \nAdolesc Gynecol. 2013 Apr;26(2):117-9. \n1.3 Surgical Therapy\n1.3.1 Role of surgical therapy in the treatment of \nendometrioma\nSurgical treatment of endometrioma is indicated \nif symptoms are or become not responder to \nmedical therapy, or  the  endometrioma increases \nin volume or is greater than 3 cm in diameter in \ninfertile patients (1,2). \n1) Practice Committee of the American Society for \nReproductive Medicine. Treatment of pelvic pain \nassociated with endometriosis: a committee opinion . \nFertil Steril. 2014 Apr;101(4):927-35. Erratum in: Fertil \nSteril. 2015; 104(2): 498.\n2) Dunselman GA, Vermeulen N, Becker C, Calhaz-\nJorge C, D’Hooghe T, De Bie B, Heikinheimo O, \nHorne AW, Kiesel L, Nap A, Prentice A, Saridogan \nE, Soriano D, Nelen W. European Society of Human \nReproduction and Embryology. ESHRE guideline:  \nmanagement of women with endometriosis . Hum \nReprod. 2014; 29(3): 400-12.\n1.3.2 Surgical modalities in the treatment of \nendometrioma.\nLaparoscopy is the gold standard for the treatment \nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n14\nof endometriosis, due to faster recovery, better \npost-operative outcome and reduced hospital \ncosts. Ovarian cystectomy  compared to laser \nvaporization or coagulation of the cystic bed,  \nlowers the number of recurrences and is associated \nwith an increase  rate of spontaneous pregnancies \nin the short and long term  (1-3). \nLaser vaporization techniques are currently \nunder evaluation in clinical studies with the aim \nof making the procedure reproducible and safe \nfor the  ovarian tissue.  A further application of \nthe CO2 Laser involves the combined  use of the \nexcisional and the ablative surgery: a large part of \nthe cystic capsule of the endometrioma is  stripped \nfollowed by vaporization of the remaining part \nof the capsule. The combined technique respects \nthe vascularization of the ovarian parenchyma, \nguarantees a greater preservation of the volume \nand the follicular count, compared to cystectomy. \nIn addition, an increase in the rate of spontaneous \npregnancies and a reduction in recurrences  (4)  \nhave been reported. \nThe damage of  ovarian parenchyma is inversely \nrelated to the experience of the surgeon  (5). \nSurgically treated patients showed an increase \nof 50% of spontaneous pregnancy  1-2 years after \nsurgery (6,7) . However, it has been shown that \nthe rate of spontaneous ovulation  (8-10), as well as \nthe response to ovarian hyperstimulation, are \nlowered after surgery (11).\n1) Carmona F, Mart_ınez-Zamora MA, Rabanal A, \nMartinez-Rom_an S, Balasch J. Ovarian cystectomy \nversus laser vaporization in the treatment of ovarian \nendometriomas: a randomized clinical trial with a \nfive-year follow-up. Fertil Steril. 2011; 96: 251–254\n2) Chapron C, Vercellini P, Barakat H, Vieira M, \nDubuisson JB. Management of ovarian endometriomas. \nHum Reprod Update. 2002 ; 8(6): 591-7.\n3) Hart, R. J., Hickey, M., Maouris, P. & Buckett, W. \nExcisional surgery versus ablative surgery for ovarian \nendometriomata. Cochrane Database of Systematic \nReviews, Issue 2; 2008: Art. No.: CD004992. \n4) Donnez J, Wyns C, Nisolle M. Does ovarian surgery \nfor endometriomas impair the ovarian response to \ngonadotropin? Fertil Steril. 2001; 76: 662–665.\n5) Muzii L, Marana R, Angioli R, et al. Histologic analysis \nof specimens from laparoscopic endometrioma \nexcision performed by different surgeons: does the \nsurgeon matter? Fertil Steril. 2011; 95: 2116–2119.\n6) De Ziegler D, Borghese B, Chapron C. Endometriosis \nand infertility: pathophysiology and management . \nLancet. 2010; 376: 730–738.\n7) Adamson DG. Laparoscopy, in vitro fertilization, \nand endometriosis: an enigma . Fertil Steril. 2005; 84: \n1582–1584.\n8) Leone Roberti Maggiore U, Scala C, Tafi E, Racca \nA, Biscaldi E, Vellone VG, Venturini PL, Ferrero S. \nSpontaneous fertility after expectant or surgical \nmanagement of rectovaginal endometriosis in women \nwith or without ovarian endometrioma: a retrospective \nanalysis. Fertil Steril. 2017 Apr;107(4):969-976.e5. doi: \n10.1016/j.fertnstert.2017.02.106.\n9) Candiani M, Barbieri M, Bottani B, Bertulessi \nC, Vignali M, Agnoli B, Somigliana E, Busacca M. \nOvarian recovery after laparoscopic enucleation of \novarian cysts: insights from echographic short-term \npostsurgical follow-up . J Minim Invasive Gynecol. \n2005; 12: 409–414.\n10) Horikawa T, Nakagawa K, Ohgi S, Kojima R, \nNakashima A, ItoM, Takahashi  Y, Saito H. The \nfrequency of ovulation from the affected ovary \ndecreases following laparoscopic cystectomy in \ninfertile women with unilateral endometrioma \nduring a natural cycle. J Assist Reprod Genet. 2008; 25: \n239–244.\n11) Somigliana E, Benaglia L, Paffoni A, Busnelli A, Vigano \nP, Vercellini P. Risks of conservative management in \nwomen with ovarian endometriomas undergoing IVF. \nHum ReprodUpdate. 2015; 21(4): 486-99.\n1.3.3 Effect of surgery on ovarian reserve\nRecent studies have shown that the laparoscopic \nstripping technique is associated with a \nreduction of the ovarian reserve, as documented \nby a reduction in the levels of postoperative \nAntimullerian hormone (AMH) (1). Otherwise \nit has been suggested that AMH is lowered \nindependently by the type of surgical procedure \nused (2) . The clinical consequences of surgical \nimpairment are limited in cases of unilateral \nendometrioma (3,4) . On the contrary, the damage \ncan become clinically relevant in cases of bilateral \nendometriomas. in this case a higher frequency \nof premature ovarian failure has been observed. \nSurgical treatment is not recommended in teens \nand young women who are searching pregnancy \nand are asymptomatic.  In view of the reduction \nof the ovarian reserve and the increased risk \nof premature ovarian failure, especially in \npatients with bilateral endometrium, several \nGuidelines for diagnosis and treatment of endometriosis\n\n15\ncryopreservation techniques are currently \navailable (5).\n1) Raffi F, Metwally M, Amer S. The impact of excision \nof ovarian endometrioma on ovarian reserve: a \nsystematic review and meta-analysis. J Clin Endocrinol \nMetab. 2012; 97(9): 3146–54. \n2) Saito N, Okuda K, Yuguchi H, et al. Compared with \ncystectomy, is ovarian vaporization of endometriotic \ncysts truly more effective in maintaining ovarian \nreserve? J Minim Invasive Gynecol. 2014; 21(5): 804–10. \n3) Demirol A, Guven S, Baykal C, Gurgan T. Effect \nof endometrioma cystectomy on IVF outcome: a \nprospective randomized study . Reprod Biomed \nOnline. 2006; 12: 639–643.\n4) Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. \nThe effect of surgical treatment for endometrioma on \nin vitro fertilization outcomes: a systematic review \nand meta-analysis. Fertil Steril. 2009; 92: 75–87.\n5) Donnez J, Dolmans MM. Cryopreservation and \ntransplantation of ovarian tissue. Clin Obstet Gynecol. \n2010; 53(4): 787-96. \n1.4 Approach to the infertile patient\n1.4.1 Endometrioma as  cause of infertility\nEndometrioma may be a cause of infertility. \nThe impact of endometrioma and its  surgical \ntreatment have been the subject of a recent \nmeta analysis including 30 retrospectives and 3 \nrandomized studies (1).\nWomen with endometrioma admitted to IVF/\nICSI have shown  a clinical  outcome similar to \nthat observed in  women whithout endometrioma, \nbut showed a lower  mean number of oocyte \nretrieved.\n1) Hamdan M, Dunselman G, Li TC, Cheong Y. The \nimpact of endometrioma on IVF/ICSI outcomes: \na systematic review and meta-analysis . Human \nReproduction Update, 2015; 21,6: 809–825.\n1.4.2 Surgical treatment before ART\nAccording to the guidelines of the European Society \nof Human Reproduction and Embryology (1), \nthe surgical treatment of endometrium > 3 cm \nin diameter improves fertility better than simple \ndrainage or only coagulation of the cyst. \nThe conservative treatment of the pseudo-\ncapsule  may be associated  with  a substantial \nrisk of recurrence  (1). Endometriosis is a recurrent \ndisease, thus he timing of management of the \ninfertile patient should take into account future \npregnancies. It is  necessary to personalize each \ntreatment taking into account other woman’s \ncharacteristics such as age. Moreover, the \npresence of  endometrioma during the IVF/ICSI \ntreatment may be associated with  difficulties  in \nthe recovery of the oocytes,  contamination of the \nfollicular fluid,  potential progression of disease,  \ncomplications in case of  pregnancy. Nevertheless, \nthe presence of endometrioma does not represent \na contraindication to IVF/ICSI treatment\n1) Dunselman GA, Vermeulen N, Becker C, Calhaz-\nJorge C, D’Hooghe T, De Bie B, Heikinheimo O, \nHorne AW, Kiesel L, Nap A, Prentice A, Saridogan \nE, Soriano D, Nelen W. European Society of Human \nReproduction and Embryology. ESHRE guideline: \nmanagement of women with endometriosis . Hum \nReprod. 2014 Mar;29(3):400-12\nSECTION 2:\nPERITONEAL ENDOMETRIOSIS\n2.1 Diagnosis\n2.1.1 Role of ultrasound and other imaging techniques\nUltrasound is recognized as the most common \ndiagnostic approach and first line imaging \ntechnique also for the evaluation of peritoneal \nendometriosis. MRI is useful when performed \nby expert operators and should be requested \nin specific cases that may benefit from further \ndiagnostic investigations, considering it is \nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n16\nburdened by high costs. \n2.1.2 Sonographic Diagnostic Criteria for peritoneal/\nsuperficial endometriosis\nThe presence of peritoneal/superficial \nendometriotic disease with associated adhesions \nshould always be evaluated in patients with \ncomplaints of cyclic/chronic pelvic pain.\nThe US “sliding sign” allows to identify with \nhigh accuracy the obliteration of the Douglas \npouch due to severe posterior adherences  (1), that \nin turn can be associated with the presence of \ndeep infiltrating endometriosis of the posterior \ncompartment.\nThis simple maneuver can easily be performed \nby operators with different levels of expertise \nand should be routinely carried out when \nscanning patients with symptoms and a clinical \nhistory possibly related to pelvic endometriosis. \nMoreover, pain complained by patients during \nultrasonographic examination in specific \nanatomic sites can guide in the detection of deep \ninfiltrating lesions.\n2.1.3 Sonographic Diagnostic Criteria for tubal \nendometriosis\nEndometriotic tubal involvement is usually \nsuperficial, resulting in adhesions that can cause \nanatomic distortion, functional impairment and \nectasia of the tubes.\nWhen tubal occlusion occurs  typical sonographic \nsigns of hydrosalpinx can be observed: a tubular \nunilocular mass with thickened walls, incomplete \nsepta and a fluid anechoic content or a dense \ncontent (ground glass) similar to endometrioma \n(haemato-salpinx).  \n2.1.4 Ultrasound evaluation in case of pelvic \nendometriosis infiltrating \nSonographic criteria for the diagnosis and \nmapping of deep pelvic endometriotic lesions were \nrecently published by a consensus of experts  (2) . \nA correct diagnosis is crucial for adequate \nclinical and/or surgical management of patients.\nDiagnostic accuracy of ultrasound performed by \nexpert operators varies from 70 to 90% depending \non the specific anatomic location  (2,3). An accurate \nevaluation of the extension of deep pelvic \nendometriosis is based on the identification, \ndescription and measurement of infiltrating \nlesions in the anterior, lateral and posterior \ncompartments (4,5). \nThe typical sonographic features of postero-\nlateral deep infiltrating endometriotic lesions \nare the following: solid hypoechoic tissue with \nirregular  margins and poor or no  vascularization  \nwhich alters the normal sonographic appearance \nof the involved anatomical site. Bladder and \nvaginal nodules can show a slight increase of \nthe vascularisation when compared to typical \npostero-lateral lesions  (2,5) . For deep infiltrating \nnodules of the anterior, lateral and posterior \nparacervical areas it is of outmost importance \nto verify the extension of the lesion and its \ndistance  from the  intra-pelvic distal tract of the \nipsilateral ureter in order to evaluate urinary tract \ninvolvement. In case of doubt or difficult ureteral \ndirect visualization, evaluation of pyelectasis \ncan be easily obtained with trans-abdominal \nultrasound in order to identify patients requiring \nurgent surgical approach (5).\nThe sonographic evaluation of deep pelvic \nendometriosis requires specific skills and a high \nlevel of expertise arising from adequate training \nand strict cooperation with pelvic surgeons, \nwhich are usually achieved in dedicated tertiary \ncenters. \nIn order to reduce potential diagnostic delay, \neven less experienced operator should be able \nto at least suspect pelvic endometriosis and \nidentify the presence of infiltrating lesions, \neventually referring affected patients to dedicated \nsonographic or MRI operators for further and \nmore accurate investigation. \n1) Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario \nG, Chou D, Kowalski D, Cooper M, Condous G. \nPrediction of pouch of Douglas obliteration in \nGuidelines for diagnosis and treatment of endometriosis\n\n17\nwomen with suspected endometriosis using a \nnew real-time dynamic transvaginal ultrasound \ntechnique: the sliding sign . Ultrasound Obstet \nGynecol. 2013;41:685-91. \n2) Guerriero S, Condous G, van den Bosch T, Valentin \nL, Leone FP, Van Schoubroeck D, Exacoustos C, \nInstallé AJ, Martins WP, Abrao MS, Hudelist G, Bazot \nM, Alcazar JL, Gonçalves MO, Pascual MA, Ajossa S, \nSavelli L, Dunham R, Reid S, Menakaya U, Bourne T, \nFerrero S, Leon M, Bignardi T, Holland T, Jurkovic D, \nBenacerraf B, Osuga Y, Somigliana E, Timmerman D. \nSystematic approach to sonographic evaluation of \nthe pelvis in women with suspected endometriosis, \nincluding terms, definitions and measurements: \na consensus opinion from the International Deep \nEndometriosis Analysis (IDEA) group .  Ultrasound \nObstet Gynecol. 2016;48:318-32.\n3) Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais \nV, Melis GB, Alcazar JL. Accuracy of transvaginal \nultrasound for diagnosis of deep endometriosis in \nuterosacral ligaments, rectovaginal septum, vagina \nand bladder: systematic review and meta-analysis . \nUltrasound Obstet 4 Gynecol. 2015;46:534-45.\n4) Exacoustos C, Manganaro L, Zupi E. Imaging for the \nevaluation of endometriosis and adenomyosis . Best \nPract Res Clin Obstet Gynaecol. 2014;28:655-81. \n5) Exacoustos C, Malzoni M, Di Giovanni A, Lazzeri \nL, Tosti C, Petraglia F, Zupi E. Ultrasound mapping \nsystem for the surgical management of deep infiltrating \nendometriosis. Fertil Steril. 2014;102:143-150.\n6) Di Giovanni A, Casarella L, Coppola M, Iuzzolino \nD, Rasile M, Malzoni M. Combined transvaginal/\ntransabdominal pelvic ultrasonographic accurately \npredict the 3 dimensions of deep infiltrating bowel \nendometriosis measured after surgery: a prospective \nstudy in specialized center. J Mimim Invasive Gynecol \n2018:18 30155-9\n2.2 Medical Therapy \n2.2.1 Medical therapy in the prevention and therapy of \npain syndrome.\nMedical treatment has a role in controlling pain \nand avoiding the progression of injuries. Studies \nhave  shown that medical therapies are effective \nonly during   their use and the symptoms often \nrecur after  the stop  of treatment  (1).\nIn  women with rectal-vaginal endometriosis,  \na review of the literature has shown that the \neffect of medical treatment in terms of pain \nreduction is substantial  (2). In the presence of pain \nsymptomatology, the use of paracetamol, NSAIDs  \nmay be associated to hormonal treatments  (3,4).\n1) Vercellini P, et al. Estrogen-progestins and \nprogestins for the management of endometriosis . \nFertility and Sterility. 2016;106(7):0015-0282. \n2) Vercellini P, et al. Medical Treatment for \nRectovaginal Endometriosis: What is the Evidence?  \nHum Reprod. 2009;24(10):2504-14.\n3) Johonson NP, et al. Consensus on current \nmanagement of endometriosis. Human Reproduction. \n2013; 28,6: 1552–15681\n4) Brown J, Crawford TJ, Datta S, Prentice A. Oral \ncontraceptives for pain associated with endometriosis. \nCochrane Database Syst Rev. 2018 May\n2.3 Surgical Therapy\n2.3.1 The aims of surgical treatment \nA conservative approach aimed at restoring \nnormal anatomical conditions with preservation \nof visceral innervation (nerve sparing techniques) \nmust be the basis of the surgical strategy. Due to the \nhigh diagnostic accuracy of imaging techniques, \nthe role of laparoscopy for purely diagnostic \npurposes is at present extremely limited  (1)  and \nhistological evidence is not currently needed \nfor treatments planning. The surgical approach \nshould be whenever possible conservative and  \nmodulated according to patient’s age and desire of \npregnancy. Non-conservative surgical treatment \nshould be considered only in cases of pain \nrefractory to any medical and surgical treatment \nin perimenopausal patients whit no childbearing \ndesire. When surgery is the treatment of choice, it \nshould be appropriately planned and performed \nby expert operators in order to avoid unnecessary \nand potentially damaging repeated procedures.\nIndications to surgical treatment for pelvic \nendometriosis are:\n• symptomatic superficial/or infiltrating \nlesions in patient not responsive or with \ncontroindications to hormonal medical therapy \n(symptoms and/or disease progression).\nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n18\n• functional organ damage (bowel subocclusion/\nocclusion, urinary tract impairment with \nrenal function compromission).\nThere is no reliable data showing superiority of \nexcision compared to the ablation of lesions in the \nsurgical treatment of peritoneal endometriosis  (2). \nHowever, the excisional technique allows \nhistological diagnosis and removal of deep \nlesions which, to a simple inspection, could \nerroneously appear as superficial. For these \nreasons, it is considered that surgical excision \nof the endometriosis should be chosen when \npossible (3). A “patient-centered” approach should \nrepresent the cornerstone in the management of \npatients with endometriosis disease.\n1) Singh SS, Suen MW. Surgery for endometriosis: beyond \nmedical therapies. Fertil Steril. 2017 Mar;107(3):549-554. \ndoi: 10.1016/j.fertnstert.2017.01.001. Epub 2017 Feb 8.\n2) Duffy J.M., Arambage K., Correa F.J., Olive D.,  \nFarquhar C., Garry R. et al. Laparoscopic surgery \nfor endometriosis . Cochrane Database Syst \nRev. 2014;:CD011031.\n3) Yeung P Jr. The laparoscopic management \nof endometriosis in patients with pelvic pain . Obstet \nGynecol Clin North Am. 2014 Sep;41(3):371-83. doi: \n10.1016/j.ogc.2014.05.002. Epub 2014 Jul 9. Review.\n2.3.2 Surgical technique\nSeveral findings (1) show the superiority of  \nlaparoscopy vs laparotomy in the treatment of \npelvic endometriosis, provided that the surgical \nprocedure is performed in highly specialized \ncenters for endoscopic pelvic surgery by operators \nwith high level of experience in the treatment of \nendometriosis (“High volume surgeons”). \nPreferably procedures should be carried out \nby surgeons with proven experience in the \nlaparoscopic treatment of  extragenital conditions, \nsuch as urological or colorectal surgical \nprocedures (“pelvic surgeon”).  \nOtherwise the treatment can be carried out by \na multidisciplinary team (gynecologist, general \nsurgeon, urologist), but in any case with proven \nexperience in the treatment of severe pelvic \nendometriosis.\n1) Jacobson TZ, Duffy JM, Barlow D, Koninckx PR \nand Garry R. Laparoscopic surgery for pelvic pain \nassociated with endometriosis . Cochrane Database \nSyst Rev 2009:CD001300.\n2.4 Approach to the infertile patient\n2.4.1 Superficial and deep endometriosis as a cause of \ninfertility\nDeep endometriosis has a marked influence on \nthe outcome of ART  (1) . Clinical pregnancy rate \n(CPR) is reduced, being also related  mainly  to  \npatient’s age,  serum value of AMH and presence \nof adenomyosis (2).\nA complete evaluation of the couple  should \nalways be offered, taking into account not only \nendometriosis as a cause of infertility, but also \nof possible concomitant pathologies (e.g. male \ninfertility).\n1) Hamdan M, Dunselman G, Li TC, Cheong Y. \nInfluence of Endometriosis on Assisted Reproductive \nTechnology Outcomes. A Systematic Review and \nMeta-analysis. Obstet Gynecol. 2015; 125:79–88. \n2) Ballester M, Oppenheimer A, Mathieu d’Argent \nE, Touboul C, Antoine JM, Nisolle M, Daraï E. Deep \ninfiltrating endometriosis is a determinant factor of \ncumulative pregnancy rate after intracytoplasmic \nsperm injection/in vitro fertilization cycles in patients \nwith endometriomas. Fertil Steril. 2012 Feb;97(2):367-72.\n2.4.2 Surgical treatment before ART\nThe impact of surgery for deep endometriosis \non fertility is  controversial. There is no level \nI evidence regarding the effect of surgery on \nfertility, thus  there is no indication to surgical \ntreatment to improve fertility (1). In case of surgery, \nif spontaneous conception does not occur after 6 \nmonths, a IVF/ICSI should be recommended.\nGuidelines for diagnosis and treatment of endometriosis\n\n19\nThere is still no clear scientific evidence of the \nassociation between miscarriage rate and deep \nendometriosis (2).\n1) Barbosa MAP, et al. Impact of endometriosis and its \nstaging on assisted reproduction outcome: systematic \nreview and meta-analysis . Ultrasound Obstet Gynecol \n2014; 44: 261–278. \n2) Jacobson TZ, Duffy JM, Barlow D, Farquhar C, \nKoninckx PR, Olive D. Laparoscopic surgery for \nsubfertility associated with endometriosis . Cochrane \nDatabase Syst Rev. 2010 Jan 20;(1):CD001398.\nSECTION 3:\nENDOMETRIOSIS IN ATYPICAL \nSITES\n3.1 Endometriosis of the abdominal wall, \ninguinal canal, umbilicus\nEndometriosis in these locations can be viewed \nwith high frequency linear probes. Endometriosis \nappears as hypoechoic areas that interrupt the \nnormal sonographic contour of the tissues.\nThese hypoechoic nodules have irregular margins \nand poor vascularity and are painful to palpation \nespecially during menses.\nAt the umbilical level, endometriosis may show \ncystic appearance with fluid dense content.\n3.2 Endometriosis in other sites\nThe presence of endometriosis in other sites \nshould be suspected on a clinical basis.\nUltrasound examination is often not useful in \ncase of deep abdominal (diaphragm) lesions and \nis non-diagnostic for thoracic and cranial lesions.\nThe ultrasound examination does not appear to \nbe diagnostic in case of endometriosis involving \nnervous structures.\n3.2.1 Bowel deep endometriosis\nThe infiltrating endometriosis nodule appears as \na hypoechoic, usually oblong thickening of the \nintestinal muscle.\nThe intestinal walls are generally visualized with \nTV approach up to the proximal sigma/distal \ndescending colon, in conditions of adequate \nacoustic window.  Intestinal nodules should \nbe measured in the three orthogonal diameters, \nincluding the depth of infiltration (anteroposterior \ndiameter).\nFurthermore, the percentage of circumference \ninvolved, the degree of stenosis, the distance \nof the caudal boundary of the nodule from the \nmargin of the anus can be evaluated  (1).\n3.2.2 Bladder endometriosis\nUreteral endometriosis may be a consequence of an \nintrinsic localization of the disease (endometriosis \nthat infiltrates the muscle) or be caused by a peri-\nureteral nodule with ureteral involvement. Both \nthe localizations can cause hydroureteronefrosis.\nIn the evaluation of infiltrating endometriosis of \nthe anterior/lateral/posterior parametrium it is \nappropriate to verify the relationship of the lesion \nwith the intrapelvic tract of the ipsilateral ureter \nin order to identify a possible involvement. In case \nof doubt, pyelectasis should be verified through \ntrans-abdominal route for the identification \nof patients with functional impairment of the \nurinary tract.\n1) Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario \nG, Chou D, Kowalski D, Cooper M, Condous G. \nPrediction of pouch of Douglas obliteration in \nwomen with suspected endometriosis using a \nnew real-time dynamic transvaginal ultrasound \ntechnique: the sliding sign . Ultrasound Obstet \nGynecol. 2013;41:685-91. \n3.3 Medical terapy\n3.3.1 Medical therapy in different location.\nIn the case of urinary endometriosis and, in \nparticular,  in case of  symptoms related to bladder \nendometriosis, there is evidence on the efficacy of \nprogestins  (dienogest) (1) or GnRH analogues (2).\nA prospective study of 500 women who underwent \nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n\nIt. J. Gynaecol. Obstet.\n2018, 30: N. 2\n20\nsurgical treatment for   intestinal endometiosis  \nshowed a low percentage of recurrence (7.8% \nin 2-6 years). The percentage of recurrence of \ndisease was lower in women who undergo \nprogestin therapy  after surgery (1%) or who had \nsuspended it for a pregnancy (2%). In women who \nstopped  treatment without getting pregnant ,the \nrecurrence rate was 20% (3). After surgery the goal \nof  hormonal therapy is  to prevent the recurrence \nof the disease and to prevent and treat the painful \nsymptomatology (4). \nAlthough most of the evidence regarding the role \nof medical therapy in preventing recurrences \nafter surgery focuses on ovarian endometriosis, \nhormonal treatment should be considered also in \ncase of deep infiltrating endometriosis.\nThere is no definitive evidence on the superiority \nof a drug on the prevention of recurrences, but \nthe limitation must be made on the basis of the \npossibility of long-term adhesion and   side effects, \ntaking into account also woman’s preferences.\n1) Angioni S, Nappi L, Pontis A, et al. Dienogest. \nA possible conservative approach in bladder \nendometriosis. Results of a pilot study . Gynecol \nEndocrinol 2015;31:406–8. \n2) Fedele L, Bianchi S, Montefusco S, Frontino G, \nCarmignani L. A gonadotropin releasing hormone \nagonist versus a continuous oral contraceptive pill in \nthe treatment of bladder endometriosis . Fertil Steril \n2008;90:183–4.\n3) Donnez J, Squifflet J. Complications, pregnancy \nand recurrence in a prospective series of 500 patients \noperated on by the shaving technique for deep \nrectovaginal endometriotic nodules . Hum Reprod \n2010;25:1949–58. \n4) Somigliana E, Vercellini P, Vigano P, Benaglia L, \nBusnelli A, Fedele L. Postoperative medical therapy \nafter surgical treatment of endometriosis: from \nadjuvant therapy to tertiary prevention . J Minim \nInvasive Gynecol. 2014;21:328–334.\n3.4 Surgical Therapy\n3.4.1 Surgical Therapy in different location\nIndications to surgery are: \n• failure of and/or controindications to medical \ntherapy\n• functional organ damage (Bowel subocclusion/\nocclusion, urinary tract impairment with \nrenal function compromission)\nSurgical techniques for the treatment of \nBowel endometriosis include excision of the \nendometriotic infiltrating lesion by nodulectomy \n(shaving or discoid resection) or by segmental \nresection. \nThere are no guidelines to determine in which \ncases segmental resection should be performed. \nInstead of conservative tecnhniques, many \noperators base their choice on the anatomic \nlocalization of the disease and clinical symptoms. \nWhenever possible, nodulectomy should be the \nprocedures of choice (1,2). However, there are some \ncases in which shaving or discoid resection are \nnot feasible and segmental resection should be \nperformed (3,4) : multiple nodules, single nodule \nwith longitudinal diameter greater than 3 cm \nand/or single nodule with deep infiltration \nof muscularis layer. In such cases, in fact, \nnodulectomy techniques could be unsatisfactory \nin terms of risk of excessive residual disease and \nan higher rate of complications.\nLaparoscopic segmental Bowel resection is a safe \nand feasible technique with low complication rate \nwhen performed by expert operators with proper \npreoperative indications  (4,5). The risk of peri and \npostoperative complications is greater in the case \nof low or ultra-low anastomosis compared to the \nlevel of the anal verge and in case of simultaneous \nopening of the vaginal wall.  The use of a transient \nileum-or Colostomy protection is discretionary.\nConcerning ureteral endometriosis, it is generally \naccepted that an intrinsic localization of the disease \nrequires ureteral resection with reanastomoses \nor bladder reimplantation, whereas in the case \nof extrinsic involvement usually ureterolisis \ncan be feasible  (6) . Ureteral endometriosis can be \nsilent but even in asymptomatic cases can lead \nto the loss of renal function  (7), so if diagnosed it \nrequires surgical approach. In case of bladder \nendometriosis the main indications for surgery \nare pain and urinary symptoms refractory to \nmedical therapy (8).\nThe standard surgical treatment for bladder \nendometriosis is segmentary bladder resection. \nLaparoscopic shaving procedures are feasible only \nfor superficial peritoneal disease. Cystoscopic \ntreatment must be avoided.\nGuidelines for diagnosis and treatment of endometriosis\n\n21\nGuidelines for diagnosis and treatment of endometriosis F. Petraglia et al.\n1) Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez \nJ. Deep endometriosis: definition, diagnosis, and \ntreatment.  Fertil Steril 2012;98: 564–71. \n2) Donnez J, Squifflet J. Complications, pregnancy and \nrecurrence in a prospective series of 500 patients operated \non by the shaving technique for deep rectovaginal \nendometriotic nodules. Hum Reprod 2010;25:1949–58.\n3) Abrao MS, Petraglia F, Falcone T, Keckstein J, Osuga \nY, Chapron C. Deep endometriosis infiltrating the recto \nsigmoid: critical factors to consider before management. \nHum. Reprod. Update 2015 May-Jun.\n4) Malzoni M, Di Giovanni A, Exacoustos C, Lannino G, \nCapece R, Perone C, Rasile M, Iuzzolino D. Feasibility and \nsafety of laparoscopic assisted Bowel segmental reection \nfor deep infiltrating endometriosis: a retrospective cohort \nstudy with description of technique. J Minim invasive \nGynecol. 2016 May-Jun.\n5) De Cicco C, Corona R, Schonman R, Mailova K, Ussia \nA, Koninckx P. Bowel resection for deep endometriosis: \na systematic review. BJOG 2011;118: 285–91. \n6) Cavaco-Gomes J, Martinho M, Gilabert-Aguilar J, \nGilabert-Estélles J. Laparoscopic management of ureteral \nendometriosis: A systematic review. Eur J Obstet Gynecol \nReprod Biol. 2016; 210:94-101. \n7) Langebrekke A, Qvigstad E. Ureteral endometriosis and \nloss of renal function: mechanisms and interpretations. \nActa Obstet Gynecol Scand 2011; 90(10):1164-6. \n8) Schonman R, Dotan Z, Weintraub AY, et al. Deep \nendometriosis inflicting the bladder: long-term \noutcomes of surgical management. Arch Gynecol Obstet \n2013;288:1323–8.","source_license":"CC0","license_restricted":false}