Management of Endometriosis in the Infertile Patient

The management of endometriosis-related infertility remains debated. However, in recent years, the role of in vitro fertilization (IVF) has progressively grown. Reasons to explain this change include (1) the improvement of the effectiveness and safety of IVF, (2) the raised awareness of the modest effectiveness of surgery, (3) the inherent risks of surgery including in particular the damage to the ovarian reserve when ovarian endometriomas have to be removed, (4) the ineffectiveness of intrauterine insemination and the possible risks of endometriosis progression associated with the use of this technique. However, IVF is not able to overcome all the potential detrimental effects of endometriosis and can actually fail. Future efforts should aim at improving the effectiveness and safety of both surgery and IVF. Fertility preservation techniques may play a role in the future, but data are currently too scanty to support its recommendation. -

- 1 Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci 2008; 1127: 92-100 - 2 CDC, Centres for Disease Control and Prevention. Reproductive Health. Assisted Reproductive Technology. National Summary and Fertility Clinic Reports; 2013 http://www.cdc.gov/art/pdf/2013-report/art_2013_national_summary_report.pdf . Accessed December 1, 2016 - 3 Leone Roberti Maggiore U, Scala C, Venturini PL, Remorgida V, Ferrero S. Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation. Hum Reprod 2015; 30 (2) 299-307 - 4 de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet 2010; 376 (9742) 730-738 - 5 Vercellini P, Meana M, Hummelshoj L, Somigliana E, Viganò P, Fedele L. Priorities for endometriosis research: a proposed focus on deep dyspareunia. Reprod Sci 2011; 18 (2) 114-118 - 6 Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 2005; 20 (8) 2309-2316 - 7 Exacoustos C, Luciano D, Corbett B , et al. The uterine junctional zone: a 3-dimensional ultrasound study of patients with endometriosis. Am J Obstet Gynecol 2013; 209 (3) 248.e1-248.e7 - 8 Vercellini P, Consonni D, Barbara G, Buggio L, Frattaruolo MP, Somigliana E. Adenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: a systematic review and meta-analysis. Reprod Biomed Online 2014; 28 (6) 704-713 - 9 Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod 2014; 29 (5) 964-977 - 10 Zheng QM, Mao HI, Zhao YJ, Zhao J, Wei X, Liu PS. Risk of endometrial polyps in women with endometriosis: a meta-analysis. Reprod Biol Endocrinol 2015; 13: 103 - 11 Di Spiezio Sardo A, Di Carlo C, Minozzi S , et al. Efficacy of hysteroscopy in improving reproductive outcomes of infertile couples: a systematic review and meta-analysis. Hum Reprod Update 2016; 22 (4) 479-496 - 12 Somigliana E, Berlanda N, Benaglia L, Viganò P, Vercellini P, Fedele L. Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimüllerian hormone level modifications. Fertil Steril 2012; 98 (6) 1531-1538 - 13 Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 2014; 10 (5) 261-275 - 14 Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod 2009; 24 (2) 254-269 - 15 Somigliana E, Vigano P, Benaglia L, Busnelli A, Vercellini P, Fedele L. Adhesion prevention in endometriosis: a neglected critical challenge. J Minim Invasive Gynecol 2012; 19 (4) 415-421 - 16 Duffy JM, Arambage K, Correa FJ , et al. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev 2014; (4) CD011031 - 17 Marcoux S, Maheux R, Bérubé S ; Canadian Collaborative Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 1997; 337 (4) 217-222 - 18 Tanahatoe SJ, Lambalk CB, Hompes PG. The role of laparoscopy in intrauterine insemination: a prospective randomized reallocation study. Hum Reprod 2005; 20 (11) 3225-3230 - 19 Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril 2012; 98 (2) 302-307 - 20 NICE - National Institute for Health and Clinical Excellence. National Collaborating Centre for Women's and Children's Health. Fertility: Assessment and Treatment for People with Fertility Problems. London (UK): 2013 :63 (Clinical guideline; no. 156) - 21 Guerriero S, Condous G, van den Bosch T , et al. 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; 48 (3) 318-332 - 22 Somigliana E, Garcia-Velasco JA. Treatment of infertility associated with deep endometriosis: definition of therapeutic balances. Fertil Steril 2015; 104 (4) 764-770 - 23 Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab 2012; 97 (9) 3146-3154 - 24 Somigliana E, Benaglia L, Paffoni A, Busnelli A, Vigano P, Vercellini P. Risks of conservative management in women with ovarian endometriomas undergoing IVF. Hum Reprod Update 2015; 21 (4) 486-499 - 25 Busacca M, Riparini J, Somigliana E , et al. Postsurgical ovarian failure after laparoscopic excision of bilateral endometriomas. Am J Obstet Gynecol 2006; 195 (2) 421-425 - 26 Benaglia L, Somigliana E, Vighi V, Ragni G, Vercellini P, Fedele L. Rate of severe ovarian damage following surgery for endometriomas. Hum Reprod 2010; 25 (3) 678-682 - 27 Berlanda N, Alberico D, Barbara G, Frattaruolo MP, Vercellini P. Exploring the relationship between endometriomas and infertility. Womens Health (Lond) 2015; 11 (2) 127-135 - 28 Kersten FA, Hermens RP, Braat DD , et al; Improvement Study Group. Overtreatment in couples with unexplained infertility. Hum Reprod 2015; 30 (1) 71-80 - 29 Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril 1997; 68 (1) 8-12 - 30 D'Hooghe TM, Denys B, Spiessens C, Meuleman C, Debrock S. Is the endometriosis recurrence rate increased after ovarian hyperstimulation?. Fertil Steril 2006; 86 (2) 283-290 - 31 van der Houwen LE, Schreurs AM, Schats R , et al. Efficacy and safety of intrauterine insemination in patients with moderate-to-severe endometriosis. Reprod Biomed Online 2014; 28 (5) 590-598 - 32 Guo SW. Recurrence of endometriosis and its control. Hum Reprod Update 2009; 15 (4) 441-461 - 33 Surrey ES. Endometriosis-related infertility: the role of the assisted reproductive technologies. BioMed Res Int 2015; 2015: 482959 - 34 Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril 2002; 77 (6) 1148-1155 - 35 Gupta S, Agarwal A, Agarwal R, Loret de Mola JR. Impact of ovarian endometrioma on assisted reproduction outcomes. Reprod Biomed Online 2006; 13 (3) 349-360 - 36 Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril 2009; 92 (1) 75-87 - 37 Harb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG 2013; 120 (11) 1308-1320 - 38 Hamdan M, Omar SZ, Dunselman G, Cheong Y. Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis. Obstet Gynecol 2015; 125 (1) 79-88 - 39 Hamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis. Hum Reprod Update 2015; 21 (6) 809-825 - 40 Yang C, Geng Y, Li Y, Chen C, Gao Y. Impact of ovarian endometrioma on ovarian responsiveness and IVF: a systematic review and meta-analysis. Reprod Biomed Online 2015; 31 (1) 9-19 - 41 Rossi AC, Prefumo F. The effects of surgery for endometriosis on pregnancy outcomes following in vitro fertilization and embryo transfer: a systematic review and meta-analysis. Arch Gynecol Obstet 2016; 294 (3) 647-655 - 42 Sanchez AM, Viganò P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M. The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary. Hum Reprod Update 2014; 20 (2) 217-230 - 43 Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group?. Hum Reprod 2015; 30 (9) 2005-2008 - 44 Bianchi PH, Pereira RM, Zanatta A, Alegretti JR, Motta EL, Serafini PC. Extensive excision of deep infiltrative endometriosis before in vitro fertilization significantly improves pregnancy rates. J Minim Invasive Gynecol 2009; 16 (2) 174-180 - 45 Opøien HK, Fedorcsak P, Byholm T, Tanbo T. Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ICSI treatment. Reprod Biomed Online 2011; 23 (3) 389-395 - 46 Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertil Steril 2005; 84 (6) 1574-1578 - 47 Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev 2007; (3) CD000155 - 48 Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 2006; (1) CD004635 - 49 Rodriguez-Tarrega E, Monzo A, Quiroga R , et al. Randomized controlled trial to evaluate the usefulness of GnRH agonist versus placebo on the outcome of IVF in infertile patients with endometriosis. Hum Reprod 2016; 31 (Suppl. 01) 322 - 50 Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. Post-operative endometriosis recurrence: a plea for prevention based on pathogenetic, epidemiological and clinical evidence. Reprod Biomed Online 2010; 21 (2) 259-265 - 51 Vercellini P, DE Matteis S, Somigliana E, Buggio L, Frattaruolo MP, Fedele L. Long-term adjuvant therapy for the prevention of postoperative endometrioma recurrence: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2013; 92 (1) 8-16 - 52 Koga K, Takamura M, Fujii T, Osuga Y. Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. Fertil Steril 2015; 104 (4) 793-801 - 53 Donnez J, Squifflet J, Jadoul P, Lousse JC, Dolmans MM, Donnez O. Fertility preservation in women with ovarian endometriosis. Front Biosci (Elite Ed) 2012; 4: 1654-1662 - 54 Bedoschi G, Turan V, Oktay K. Fertility preservation options in women with endometriosis. Minerva Ginecol 2013; 65 (2) 99-103 - 55 Seyhan A, Ata B, Uncu G. The impact of endometriosis and its treatment on ovarian reserve. Semin Reprod Med 2015; 33 (6) 422-428 - 56 Somigliana E, Viganò P, Filippi F , et al. Fertility preservation in women with endometriosis: for all, for some, for none?. Hum Reprod 2015; 30 (6) 1280-1286 - 57 Sönmezer M, Taşkın S. Fertility preservation in women with ovarian endometriosis. Womens Health (Lond) 2015; 11 (5) 625-631 - 58 Carrillo L, Seidman DS, Cittadini E, Meirow D. The role of fertility preservation in patients with endometriosis. J Assist Reprod Genet 2016; 33 (3) 317-323 - 59 Donnez J, Squifflet J, Dolmans MM, Martinez-Madrid B, Jadoul P, Van Langendonckt A. Orthotopic transplantation of fresh ovarian cortex: a report of two cases. Fertil Steril 2005; 84 (4) 1018 - 60 Elizur SE, Chian RC, Holzer HE, Gidoni Y, Tulandi T, Tan SL. Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation. Fertil Steril 2009; 91 (1) 293.e1-293.e3 - 61 Oktay K, Oktem O. Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. Fertil Steril 2010; 93 (3) 762-768 - 62 Garcia-Velasco JA, Domingo J, Cobo A, Martínez M, Carmona L, Pellicer A. Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril 2013; 99 (7) 1994-1999 - 63 Cobo A, García-Velasco JA, Coello A, Domingo J, Pellicer A, Remohí J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016; 105 (3) 755-64.e8 - 64 Vercellini P, Giudice LC, Evers JL, Abrao MS. Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal. Hum Reprod 2015; 30 (9) 1996-2004 - 65 Vigano P, Corti L, Berlanda N. Beyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis. Fertil Steril 2015; 104 (4) 802-812 - 66 Brosens IA, Lier MC, Mijatovic V, Habiba M, Benagiano G. Severe spontaneous hemoperitoneum in pregnancy may be linked to in vitro fertilization in patients with endometriosis: a systematic review. Fertil Steril 2016; 106 (3) 692-703 - 67 Leone Roberti Maggiore U, Ferrero S, Mangili G , et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update 2016; 22 (1) 70-103 - 68 Silver RM. Abnormal placentation: placenta previa, vasa previa, and placenta accreta. Obstet Gynecol 2015; 126 (3) 654-668 - 69 Aguilar HN, Mitchell BF. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update 2010; 16 (6) 725-744 - 70 Stephansson O, Kieler H, Granath F, Falconer H. Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Hum Reprod 2009; 24 (9) 2341-2347 - 71 Grady R, Alavi N, Vale R, Khandwala M, McDonald SD. Elective single embryo transfer and perinatal outcomes: a systematic review and meta-analysis. Fertil Steril 2012; 97 (2) 324-331 - 72 Hubinont C, Lewi L, Bernard P, Marbaix E, Debiève F, Jauniaux E. Anomalies of the placenta and umbilical cord in twin gestations. Am J Obstet Gynecol 2015; 213 , (4 Suppl): S91-S102