Management Challenges of Deep Infiltrating Endometriosis

Document Type : Review Article


1 Department of Surgical Sciences, University of Cagliari, Cagliari, Italy

2 Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt

3 Department of Obstetrics and Ginecology, ‘Valle d’Itria’ Hospital, Martina Franca, Taranto, Italy

4 Department of Obstetrics and Gynecology, 2nd University Clinic of Obstetrics and Gynecology, Aristotele University of Thessaloniki, Thessaloniki, Greece

5 Department of Surgical Sciences, University of Cagliari, Cagliari, Italy;


Deep infiltrating endometriosis (DIE) is the most aggressive of the three phenotypes that constitute endometriosis.
It can affect the whole pelvis, subverting the anatomy and functionality of vital organs, with an important negative
impact on the patient’s quality of life. The diagnosis of DIE is based on clinical and physical examination, instrumental
examination, and, if surgery is needed, the identification and biopsy of lesions. The choice of the best therapeutic
approach for women with DIE is often challenging. Therapeutic options include medical and surgical treatment, and
the decision should be dictated by the patient’s medical history, disease stage, symptom severity, and personal choice.
Medical therapy can control the symptoms and stop the development of pathology, keeping in mind the side effects
derived from a long-term treatment and the risk of recurrence once suspended. Surgical treatment should be proposed
only when it is strictly necessary (failed hormone therapy, contraindications to hormone treatment, severity of symptoms,
infertility), preferring, whenever possible, a conservative approach performed by a multidisciplinary team. All
therapeutic possibilities have to be explained by the physicians in order to help the patients to make the right choice
and minimize the impact of the disease on their lives.


1. Angioni S. New insights on endometriosis. Minerva Ginecol. 2017; 69(5): 438-439.
2. Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endo­metriosis: a large population-based database study from a health­care provider with 2 million members. BJOG. 2018; 125(1): 55-62.
3. Alio L, Angioni S, Arena S, Bartiromo L, Bergamini V, Berlanda N, et al. Endometriosis: seeking optimal management in women ap­proaching menopause. Climacteric. 2019; 22(4): 329-338.
4. Vitale SG, La Rosa VL, Rapisarda AMC, Laganà AS. Impact of en­dometriosis on quality of life and psychological well-being. J Psy­chosom Obstet Gynaecol. 2017; 38(4): 317-319.
5. Šalamun V, Verdenik I, Laganà AS, Vrtačnik-Bokal E. Should we consider integrated approach for endometriosis-associated infertil­ity as gold standard management? Rationale and results from a large cohort analysis. Arch Gynecol Obstet. 2018; 297(3): 613-621.
6. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endome­triosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997; 68(4): 585-596.
7. Koninckx PR, Ussia A, Adamyan LV, Wattiez A, Donnez J. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012; 98(3): 564-571.
8. Nisenblat V, Bossuyt PM, Farquhar C, Johnson N, Hull ML. Im­aging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016: 2(2): CD009591.
9. Deiana D, Gessa S, Anardu M, Daniilidis A, Nappi L, D’Alterio MN, et al. Genetic of endometriosis: a comprehensive review. Gynecol Endocrinol. 2019; 35(7): 553-558.
10. Angioni S, D’Alterio MN, Coiana A, Anni F, Gessa S, Deiana D. Genetic characterization of endometriosis patients: review of the literature and a prospective cohort study on a Mediterranean population. Int J Mol Sci. 2020; 21(5): 1765.
11. Lagana AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The pathogenesis of endometriosis: molecular and cell biology insights. Int J Mol Sci. 2019; 20(22): 5615.
12. Viganò D, Zara F, Pinto S, Loddo E, Casula L, Soru MB, et al. How is small bowel permeability in endometriosis patients? A case con­trol pilot study. Gynecol Endocrinol. 2020; 36(11): 1-5.
13. Tosti C, Pinzauti S, Santulli P, Chapron C, Petraglia F. Pathogenetic mechanism of deep infiltrating endometriosis. Reprod Sci. 2015; 22(9): 1053-1059.
14. Gargett CE, Schwab KE, Brosens JJ, Puttemans P, Benagiano G, Brosens I. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis. Mol Hum Reprod. 2014; 20(7): 591-598.
15. Laganà AS, Salmeri FM, Vitale SG, Triolo O, Götte M. Stem cell trafficking during endometriosis: may epigenetics play a pivotal role? Reprod Sci. 2018; 25(7): 978-979.
16. De Pereira LB, Braga NP, Mendonca M, Moro L, Geber S. Apopto­sis of ectopic endometrial cells is impaired in women with endome­triosis. J Endometr Pelvic Pain Disord. 2012; 4(1): 17-20
17. Machado DE, Abrao MS, Berardo PT, Takiya CM, Nasciutti LE. Vascular density and distribution of vascular endothelial growth actor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum. Fertil Steril. 2008; 90(1): 148-155.
18. Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, et al. Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Hum Re­prod. 2003; 18(1): 157-161.
19. Triolo O, Laganà AS, Sturlese E. Chronic pelvic pain in endometrio­sis: an overview. J Clin Med Res. 2013; 5(3): 153-163.
20. Noventa M, Scioscia M, Schincariol M, Cavallin F, Pontrelli G, Vir­gilio B, et al. Imaging modalities for diagnosis of deep pelvic en­dometriosis: comparison between trans-vaginal sonography, rectal endoscopy sonography and magnetic resonance imaging. A head-to-head meta-analysis. Diagnostics (Basel). 2019; 9(4): E225.
21. Faccioli N, Foti G, Manfredi R, Mainardi P, Spoto E, Ruffo G, et al. Evaluation of colonic involvement in endometriosis: double-contrast barium enema vs. magnetic resonance imaging. Abdom Imaging. 2010; 35(4): 414-421.
22. Vercellini P, Viganò P, Buggio L, Somigliana E. We Can Work It Out: The hundred years' war between experts of surgical and medical treatment for symptomatic deep endometriosis. J Minim Invasive Gynecol. 2018; 25(3): 356-359.
23. Szubert M, Zietara M, Suzin J. Conservative treatment of deep in­filtrating endometriosis: review of existing options. Gynecol Endo­ D’Alteriocrinol. 2018; 34(1): 10-14.
24. Parazzini F, Vigano P, Candiani M, Fedele L. Diet and endometriosis risk: a literature review. Reprod Biomed Online. 2013; 26(4): 323-336.
25. Stochino Loi E, Pontis A, Cofelice V, Pirarba S, Fais MF, Daniilidis A, et al. Effect of ultramicronized-palmitoylethanolamide and co-micronized palmitoylethanolamide/polydatin on chronic pelvic pain and quality of life in endometriosis patients: An open-label pilot study. Int J Womens Health. 2019; 11: 443-449.
26. Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Remor­gida V. Norethisterone acetate in the treatment of colorectal endo­metriosis: a pilot study. Hum Reprod. 2010; 25(1): 94-100.
27. Leonardo-Pinto JP, Benetti-Pinto CL, Cursino K, Yela DA. Dien­ogest and deep infiltrating endometriosis: the remission of symp­toms is not related to endometriosis nodule remission. Eur J Obstet Gynecol Reprod Biol. 2017; 211: 108-111.
28. Yela D, Kajikawa P, Donati L, Cursino K, Giraldo H, Benetti-Pinto CL. Deep infiltrating endometriosis treatment with dienogest: a pilot study. J Endometr Pelvic Pain Disord. 2015; 7(1): 33-37.
29. Angioni S, Nappi L, Pontis A, Sedda F, Luisi S, Mais V, et al. Dien­ogest. A possible conservative approach in bladder endometriosis. Results of a pilot study. Gynecol Endocrinol. 2015; 31(5): 406-408.
30. Angioni S, Pontis A, Malune ME, Cela V, Luisi S, Litta P, et al. Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study. Gynecol Endocrinol. 2020; 36(1): 84-86.
31. Tarjanne S, Ng CHM, Manconi F, Arola J, Mentula M, Maneck B, et al. Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis. Acta Obstet Gynecol Scand. 2015; 94(7): 693-700.
32. Casper RF. Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertil Steril. 2017; 107(3): 533-536.
33. Dunselman GAJ, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29(3): 400-412.
34. Fedele L, Bianchi S, Zanconato G, Tozzi L, Raffaelli R. Gonadotropin releasing hormone agonist treatment for endometriosis of the rec­tovaginal septum. Am J Obstet Gynecol. 2000; 183(6): 1462-1467.
35. Roman H, Saint-Ghislain M, Milles M, Marty N, Hennetier C, Moatassim S, et al. Improvement of digestive complaints in women with severe colorectal endometriosis benefiting from continuous amenorrhoea triggered by triptoreline. A prospective pilot study. Gynecol Obstet Fertil. 2015; 43(9): 575-581.
36. Angioni S, Pontis A, Dessole M, Surico D, De Cicco Nardone C, Melis I. Pain control and quality of life after laparoscopic en-block resection of deep infiltrating endometriosis (DIE) vs. incomplete surgical treatment with or without GnRHa administration after sur­gery. Arch Gynecol Obstet. 2015; 291(2): 363-370.
37. Melis GB, Neri M, Corda V, Malune ME, Piras B, Pirarba S, et al. Overview of elagolix for the treatment of endometriosis. Expert Opin Drug Metab Toxicol. 2016; 12(5): 581-588.
38. Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007; (4): CD000068.
39. Razzi S, Luisi S, Calonaci F, Altomare A, Bocchi C, Petraglia F. Ef­ficay of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis. Fertil Steril. 2007; 88(4): 789-794.
40. Patwardhan S, Nawathe A, Yates D, Harrison GR, Khan KS. Sys­tematic review of the effects of aromatase inhibitors on pain associ­ated with endometriosis. BJOG. 2008; 115: 818-822.
41. Ferrero S, Venturini PL, Gillott DJ, Remorgida V. Letrozole and norethisterone acetate versus letrozole and triptorelin in the treat­ment of endometriosis related pain symptoms: a randomized con­trolled trial. Reprod Biol Endocrinol. 2011; 9: 88.
42. Bedaiwy MA, Alfaraj S, Yong P, Casper R. New developments in the medical treatment of endometriosis. Fertil Steril. 2017; 107(3): 555-565.
43. Kulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with baze­doxifene, a selective estrogen receptor modulator, causes regres­sion of endometriosis in a mouse model. Endocrinology. 2011; 152(8): 3226-3232.
44. Laganà AS, La Rosa VL. Multidisciplinary management of endo­metriosis: current strategies and future challenges. Minerva Med. 2020; 111(1): 18-20.
45. Ceccaroni M, Clarizia R, Roviglione G, Ruffo G. Neuro-anatomy of the posterior parametrium and surgical considerations for a nerve-sparing approach in radical pelvic surgery. Surg Endosc. 2013; 27(11): 4386-4394.
46. Ceccaroni M, Clarizia R, Bruni F, D’Urso E, Gagliardi ML, Rovigli­one G, et al. Nerve-sparing laparoscopic eradication of deep en­dometriosis with segmental rectal and parametrial resection: the Negrar method. A single-center, prospective, clinical trial. Surg En­dosc. 2012; 26(7): 2029-2045.
47. Angioni S, Peiretti M, Zirone M, Palomba M, Mais B, Gomel V, et al. Lap­aroscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up. Hum Reprod. 2006; 21(6): 1629-1634.
48. Donnez O, Roman H. Choosing the right surgical technique for deep endometriosis: shaving, disc excision, or bowel resection? Fertil Steril. 2017; 108(6): 931-942.
49. Laganà AS, Vitale SG, Trovato MA, Palmara VI, Rapisarda AMC, Granese R, et al. Full-thickness excision versus shaving by lapa­roscopy for intestinal deep infiltrating endometriosis: rationale and potential treatment options. Biomed Res Int. 2016; 2016: 3617179.
50. Kondo W, Bourdel N, Tamburro S, Cavoli D, Jardon K, Rabishong B, et al. Complications after surgery for deeply infiltrating pelvic endometriosis. BJOG. 2011; 118(3): 292-298.
51. Roman H, Milles M, Vassilieff M, Resh B, Tuech JJ, Huet E, et al. Long-term functional outcomes following colorectal resection ver­sus shaving for rectal endometriosis. Am J Obstet Gynecol. 2016; 215(6): 762.e1-762.e9.
52. Meuleman C, Tomassetti C, D’Hoore A, Cleynenbreugel BV, Pen­ninckx F, Vergote I, et al. Surgical treatment of deeply infiltrating endometriosis with colorectal involvment. Hum Reprod Update. 2011; 17(3): 311-326.
53. Gordon SJ, Mather PJ, Woods R. Use of the CEEA stapler to avoid ultra-low segmental resection of a full-thickness rectal endometri­otic nodule. J Am Assoc Gynecol Laparosc. 2001; 8(2): 312-316.
54. Roman H, Darwish B, Bridoux V, Chati R, Kermiche S, Coget J, et al. Functional outcomes after disc excision in deep endometriosis of the rectum using transanal staplers: a series of 111 consecutive patients. Fertil Steril. 2017; 107(4): 977-986.
55. Abrao MS, Borrelli GM, Clarizia R, Kho RM, Ceccaroni M. Strate­gies for management of colorectal endometriosis. Semin Reprod Med. 2017; 35(1): 65-71.
56. Tarjanne S, Heikinheimo O, Mentula M, Härkki P. Complications and long-term follow-up on colorectal resections in the treatment of deep infiltrating endometriosis extending to bowel wall. Acta Obstet Gynecol Scand. 2015; 94(1): 72-79.
57. Raffaelli R, Garzon S, Baggio S, Genna M, Pomini P, Laganà AS, et al. Mesenteric vascular and nerve sparing surgery in laparoscopic segmental intestinal resection for deep infiltrating endometriosis. Eur J Obstet Gynecol Reprod Biol. 2018; 231: 214-219.
58. Chapron C, Chiodo I, Leconte M, Amsellem-Ouazana D, Chopin N, Borghese B, et al. Severe ureteral endometriosis: the intrinsic type is not so rare after complete surgical exeresis of deep endometri­otic lesions. Fertil Steril. 2010; 93(7): 2115-2120.
59. Butticè S, Laganà AS, Mucciardi G, Marson F, Tefik T, Netsch C, et al. Different patterns of pelvic ureteral endometriosis. What is the best treatment? Results of a retrospective analysis. Arch Ital Urol Androl. 2016; 88(4): 266-269.
60. Soriano D, Schonman R, Nadu A, Lebovitz O, Schiff E, Seidman DS, et al. Multidisciplinary team approach to management of severe en­dometriosis affecting the ureter: long-term outcome data and treat­ment algorithm. J Minim Invasive Gynecol. 2011; 18(4): 483-488.
61. Bosev D, Nicoll LM, Bhagan L, Lemyre M, Payne C, Gill H, et al. Laparoscopic management of ureteral endometriosis: the Stanford University Hospital experience with 96 consecutive cases. J Urol. 2009; 182(6): 2748-2752.
62. Uccella S, Cromi A, Casarin J, Bogani G, Pinelli C, Serati M, et al. Laparoscopy for ureteral endometriosis: surgical details, long-term follow-up, and fertility outcomes. Fertil Steril. 2014; 102(1): 160-166.
63. Saccardi C, Vitagliano A, Litta P. Bladder endometriosis: a summary of current evidence. Minerva Ginecol. 2017; 69(5): 468-476.
64. Seracchioli R, Mabrouk M, Montanari G, Manuzzi L, Concetti S, Venturoli S. Conservative laparoscopic management of urinary tract endometriosis (UTE): surgical outcome and long-term follow-up. Fertil Steril. 2010; 94(3): 856-861.
65. Fedele L, Bianchi S, Zanconato G, Bergamini V, Berlanda N, Car­mignani L. Long-term follow-up after conservative surgery for blad­der endometriosis. Fertil Steril. 2005; 83(6): 1729-1733.
66. Pontis A, Nappi L, Sedda F, Multinu F, Litta P, Angioni S. Manage­ment of bladder endometriosis with combined transurethral and laparoscopic approach. Follow-up of pain control, quality of life, and sexual function at 12 months after surgery. Clin Exp Obstet Gynecol. 2016; 43(6): 836-839.