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Ovarian endometriosis and infertility: in vitro fertilization (IVF) or surgery as the first approach?

2018; Elsevier BV; Volume: 110; Issue: 7 Linguagem: Inglês

10.1016/j.fertnstert.2018.10.003

1556-5653

Bruce A. Lessey, Stephan Gordts, Olivier Donnez, Edgardo Somigliana, Charles Chapron, Juan A. García-Velasco, Jacques Donnez,

Uterine Myomas and Treatments

IVF is commonly applied to all indications for infertility, but increasingly unexplained causes predominate (www.sart.org). Specifically, endometriosis is listed as the primary diagnosis in less than 4% of cases in the United States, primarily because laparoscopy is not performed for the basic infertility workup, as it once was (1Feinberg E.C. Levens E.D. DeCherney A.H. Infertility surgery is dead: only the obituary remains?.Fertil Steril. 2008; 89: 232-236Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar). Unexplained cases of infertility show a high prevalence of endometriosis (2Nakagawa K. Ohgi S. Horikawa T. Kojima R. Ito M. Saito H. Laparoscopy should be strongly considered for women with unexplained infertility.J Obstet Gynaecol Res. 2007; 33: 665-670Crossref PubMed Scopus (33) Google Scholar, 3Bonneau C. Chanelles O. Sifer C. Poncelet C. Use of laparoscopy in unexplained infertility.Eur J Obstet Gynecol Reprod Biol. 2012; 163: 57-61Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar). Visible endometriosis such as endometriomas present a special challenge, especially since ovarian reserve may be compromised when ovarian surgery is performed. In lieu of reliable biomarkers, decisions on surgery for endometriosis have depended less on available data and even more on what the physician specialist prefers: scalpels or IVF retrieval needles. In this debate, the elephant in the room is not the endometrioma, but rather the vast number of undiagnosed cases of endometriosis that are hidden within the population of IVF clients. Given that few providers are actively looking for endometriosis anymore, it is safe to say that the majority of women with endometriosis and infertility who are attempting IVF do not know they have this disease. Why does it matter? Most practitioners do not seem convinced that endometriosis is a cause of IVF failure. Based on meta-analyses, the impact indeed seems small (4Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (607) Google Scholar). The evidence, however, is subjective and strongly influenced by ascertainment bias and study design. Most studies on the impact of endometriosis on IVF outcomes are based on women with a prior diagnosis and, therefore, past treatment. The much larger group with undiagnosed endometriosis remains uncounted. With the advent of reliable biomarkers for endometriosis including BCL6 (5Evans-Hoeker E. Lessey B.A. Jeong J.W. Savaris R.F. Palomino W.A. Yuan L. et al.Endometrial BCL6 overexpression in eutopic endometrium of women with endometriosis.Reprod Sci. 2016; 23: 1234-1241Crossref PubMed Scopus (40) Google Scholar, 6Yoo J.-Y. Kim T.H. Fazleabas A.T. Palomino W.A. Ahn S.H. Tayade C. et al.KRAS activation and over-expression of SIRT1/BCL6 contributes to the pathogenesis of endometriosis and progesterone resistance.Sci Rep. 2017; 7: 6765Crossref PubMed Scopus (63) Google Scholar), newer studies suggest that IVF outcomes are indeed compromised by the presence of unrecognized endometriosis (7Almquist L.D. Likes C.E. Stone B. Brown K.R. Savaris R. Forstein D.A. et al.Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study.Fertil Steril. 2017; 108: 1063-1069Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar). Future randomized controlled trials to address this “fertile battle” question must address two questions: [1] Does untreated endometriosis alter IVF outcomes and [2] is surgery helpful? Other debates might include the mechanism of these implantation defects (ovarian versus endometrial) and how big an endometrioma has to be to result in defects in endometrial receptivity. For the patient, ironically, the important question that is rarely asked is, “Could I conceive without IVF if my endometriosis was first diagnosed and treated?” Most couples never think to ask that question as they have been infertile for a year or more and assume that they need IVF to conceive. In the United States, where coverage for IVF is often poor or nonexistent, the answer to this question could have significant ramifications, especially for couples struggling to afford health care for their infertility. The success rates for IVF remain below 50%, even when euploid embryos are transferred (8Harton G.L. Munné S. Surrey M. Grifo J. Kaplan B. McCulloh D.H. et al.Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization.Fertil Steril. 2013; 100: 1695-1703Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar). Surgical treatment of endometriosis improves outcomes and allows couples to conceive, often without IVF (9Littman 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: 1574-1578Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar). Endometrial receptivity defects appear to be a primary mechanism by which endometriosis impacts IVF outcome (based on sibling ETs) (10Prapas Y. Goudakou M. Matalliotakis I. Kalogeraki A. Matalliotaki C. Panagiotidis Y. et al.History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes.Reprod Biomed Online. 2012; 25: 543-548Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar), although ovarian inflammation as a mechanism cannot be ruled out (11Marcoux S. Maheux R. Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.N Engl J Med. 1997; 337: 217-222Crossref PubMed Scopus (830) Google Scholar). The argument for surgery is clear when symptoms of pelvic pain are present but less obvious in asymptomatic women with infertility. In the case of unexplained infertility, treatment of mild disease provides a more favorable outcome than expectant management (11Marcoux S. Maheux R. Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.N Engl J Med. 1997; 337: 217-222Crossref PubMed Scopus (830) Google Scholar). Establishing a diagnosis and providing improved chances for conception before IVF will also lead to advances in overall IVF success rates across the board. The choice to perform surgery demonstrates a commitment to optimal patient care. Like an auto mechanic who changes the oil but does not notice the flat tire, a reproductive specialist who relies solely on IVF is doing a great disservice to his or her patients. A complete evaluation of female factor infertility includes diagnosis and treatment of endometriosis, which, after all, is quite common in this population. This failing affects millions of women each year, representing a large percentage of the population of infertile couples. We need to take off our blinders and face the facts: endometriosis is a primary cause of infertility and reduces the chance of conception, even in the setting of IVF. Why is it that the discussion regarding the decision to treat with IVF or surgery involves only the endometrioma and is not questioned for other benign ovarian cysts? Ovarian endometrioma is distinguished from other benign ovarian cysts by the complexity of the disease and because it causes diminished fertility. First, there is the absence of a cystic wall separating the cystic structure from the normal ovarian tissue (12Donnez J. Nisolle M. Gillet N. Smets M. Bassil S. Casanas-Roux F. Large ovarian endometriomas.Hum Reprod. 1996; 11: 641-646Crossref PubMed Google Scholar). The illusion of the existence of a cystic wall is created by the fibrosis underlying the pseudocystic structure. Second, fibrosis is already present in endometriomas <4 cm with the presence of significantly more morphologically atretic early follicles compared with the cortex of the contralateral normal ovary, suggesting the deleterious impact of the endometrioma itself on the ovarian reserve (13Kitajima M. Dolmans M.-M. Donnez O. Masuzaki H. Soares M. Donnez J. Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas.Fertil Steril. 2014; 101: 1031-1037Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar). Third, independent from the technique used, each surgery carries the risk of damaging the follicular reserve. This contrasts with other benign ovarian cysts that have an intraovarian localization and are delineated by a well-defined cystic wall (14Muzii L. Bianchi A. Crocè C. Manci N. Panici P.B. Laparoscopic excision of ovarian cysts: is the stripping technique a tissue-sparing procedure?.Fertil Steril. 2002; 77: 609-614Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar, 15Alborzi S. Foroughinia L. Kumar P.V. Asadi N. Alborzi S. A comparison of histopathologic findings of ovarian tissue inadvertently excised with endometrioma and other kinds of benign ovarian cyst in patients undergoing laparoscopy versus laparotomy.Fertil Steril. 2009; 92: 2004-2007Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). The impaired ovarian reserve caused by the disease itself and the potential harm done by surgery are challenging for the treatment (16Niewe'glowska D. Hajdyla-Banas I. Pitynski K. Banas T. Grabowska O. Juszczyk G. et al.Age-related trends in anti-Mullerian hormone serum level in women with unilateral and bilateral ovarian endometriomas prior to surgery.Reprod Biol Endocrinol. 2015; 13: 128Google Scholar). Several studies have documented the delay of diagnosis in women with endometriosis (17Arruda M.S. Petta C.A. Abrão M.S. Benetti-Pinto C.L. Time elapsed from onset of symptoms of endometriosis in a cohort study of Brazilian women.Hum Reprod. 2003; 18: 756-759Crossref PubMed Scopus (236) Google Scholar, 18Hudelist G. Fritzer N. Thomas A. Niehues C. Oppelt P. Haas D. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (216) Google Scholar). This delay of diagnosis is certainly unacceptable in adolescents with pain as such delay can cause serious damage in young women and impair their future fertility. Although progressivity is hard to prove, progression in adolescents has been suggested by Unger and Laufer (19Unger C.A. Laufer M.R. Progression of endometriosis in non-medically managed adolescents: a case series.J Pediatr Adolesc Gynecol. 2011; 24: e21-e23Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar) and Reese et al. (20Reese K.A. Reddy S. Rock J.A. Endometriosis in an adolescent population: the Emory experience.J Pediatr Adolesc Gynecol. 1997; 9: 125-128Abstract Full Text PDF Google Scholar), and progression was laparoscopically proven in 31% of the patients in a study by Savaris et al. (21Savaris R.F. Nichols C. Lessey B.A. Endometriosis and the enigmatic question of progression.J Endometr Pelvic Pain Disord. 2014; 6: 121-126Google Scholar). In addition, Saridogan concluded that the endometriosis can be progressive in a significant number of adolescents (22Saridogan E. Adolescent endometriosis.Eur J Obstet Gynecol Reprod Biol. 2017; 209: 46-49Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar). In the adolescent, endometriosis is characterized by the presence of red lesions, adhesion formation, and the presence of endometrioma. Recent reports on the presence of endometriosis in adolescents reveal a high incidence of severe endometriosis stages III–IV due to the presence of extensive adhesions and the ovarian endometrioma (23Brosens I. Gordts S. Benagiano G. Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.Hum Reprod. 2013; 28: 2026-2031Crossref PubMed Scopus (92) Google Scholar). The delayed diagnosis and treatment contrast with the progression of the disease that shows an increase in cyst size and progressive smooth muscle metaplasia. Inspection of the inner wall of a small endometrioma of 1–2 cm in size performed by transvaginal hydrolaparoscopy clearly shows a strong inflammatory reaction with neoangiogenesis and the presence of active endometrium-like tissue (24Gordts S. Puttemans P. Gordts Sy Valkenburg M. Brosens I. Campo R. Transvaginal endoscopy and small ovarian endometriomas: unravelling the missing link?.Gynecol Surg. 2014; 11: 3-7Google Scholar) (Fig. 1). As such, size is not an indicator for the aggressiveness of the disease and the decision whether to treat with surgery should not be based on this parameter. The size of 3 cm used in the European Society of Human Reproduction and Embryology guidelines (25Dunselman G.A.J. 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: 400-412Crossref PubMed Scopus (1316) Google Scholar) is purely arbitrary and has no scientific background. One of the papers used to support this recommendation clearly showed that there was no statistically significant difference in the number of follicles when stimulating for IVF in operated endometriomas less than or greater than 3 cm using a CO2 ablative surgery (26Donnez J. Wyns C. Nisolle M. Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin?.Fertil Steril. 2001; 76: 662-665Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). Early diagnosis and treatment of endometriomas increase the chances that fibrosis is limited and vascularization of the ovarian bed is preserved; surgery in an early stage on smaller cysts will cause less ovarian trauma. Minimally invasive ablative surgery is preferred. Older and new data show the beneficial effect of surgery in reducing pain and in obtaining a spontaneous pregnancy rate of 50%–60% within a delay of 12 months after the procedure (27Gordts S. Boeckx W. Brosens I. Microsurgery of endometriosis in infertile patients.Fertil Steril. 1984; 42: 520-525Abstract Full Text PDF PubMed Scopus (44) Google Scholar, 28Vercellini P. Fedele L. Aimi G. De Giorgi O. Consonni D. Crosignani P.G. Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current classification system.Hum Reprod. 2006; 21: 2679-2685Crossref PubMed Scopus (166) Google Scholar, 29Donnez J. Chantraine F. Nisolle M. The efficacy of medical and surgical treatment of endometriosis-associated infertility: arguments in favour of a medico-surgical approach.Hum Reprod Update. 2002; 8: 89-94Crossref PubMed Scopus (61) Google Scholar). If on the basis of these data we can offer an individual patient a serious chance of a spontaneous conception, surgery should be the first treatment option. The prerequisite for this is that an experienced reproductive surgeon should perform it. Unfortunately, there is a direct correlation between the increase of liberal referral of patients to an IVF program and the increase of inexperienced surgeons, leading to a vicious cycle. Stand-alone IVF centers without the possibility of performing reproductive surgery or without collaboration and proven referral to a center performing reproductive surgery will not be able to provide patients with an accurate and correct treatment modality. Referral of a couple for IVF treatment should not be based only on the diagnosis of endometriosis but mainly on concomitant fertility-impairing factors. Only surgery in the early stages of the disease can avoid further impairment of fertility caused by the progressivity of the disease, can be performed with a minimal trauma to the ovary, and offers the possibility for a spontaneous conception and, when present, relief of pain. Several arguments are proposed in favor of surgical treatment of ovarian endometriosis. Studies have already shown decreased pain and increased fertility (up to more than 50%) after surgical treatment of endometriomas (12Donnez J. Nisolle M. Gillet N. Smets M. Bassil S. Casanas-Roux F. Large ovarian endometriomas.Hum Reprod. 1996; 11: 641-646Crossref PubMed Google Scholar, 30Hart R.J. Hickey M. Maouris P. Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata.Cochrane Database Syst Rev. 2008; 16: CD004992Google Scholar). It is important to note that ovarian endometriosis itself may compromise fertility. Indeed, it has been shown that ovaries with endometriotic cysts already exhibit reduced follicle numbers (31Maneschi F. Marasa L. Incadela S. Mazzarese M. Zupi E. Ovarian cortex surrounding benign neoplasms: a histologic study.Am J Obstet Gynecol. 1993; 169: 388-393Abstract Full Text PDF PubMed Scopus (182) Google Scholar, 32Schubert B. Canis M. Darcha C. Artonne C. Pouly J.L. Dechelotte P. et al.Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation.Hum Reprod. 2005; 20: 1786-1792Crossref PubMed Scopus (81) Google Scholar, 33Kitajima M. Defrere S. Dolmans M.M. Colette S. Squifflet J. et al.Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis.Fertil Steril. 2011; 96: 685-691Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). According to Kitajima et al., the “burnout hypothesis” may explain the mechanism partly responsible for the reduced ovarian reserve in women with endometriomas (33Kitajima M. Defrere S. Dolmans M.M. Colette S. Squifflet J. et al.Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis.Fertil Steril. 2011; 96: 685-691Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). Formation of endometriomas may cause focal inflammation in the ovarian cortex. This inflammation could result in structural alteration of the ovarian cortex, which manifests as massive fibrosis and loss of the cortex-specific stroma that maintains follicular nests. Focal loss of follicular density may be associated with a vicious circle of dysregulated folliculogenesis that eventually results in burnout of the stockpile of dormant follicles. Indications for surgery should be adapted to the age of the patient, her symptoms, whether she wants to conceive soon, previous surgery, other possible indications for IVF, and endometrioma size. Patients wishing to conceive and without other infertility factors or previous surgery will clearly benefit from surgical management. Even if IVF is required afterward, pregnancy rates will not be adversely affected (34Nickkho-Amiry M. Savant R. Majumder K. Edi-O'sagie E. Akhtar M. The effect of surgical management of endometrioma on the IVF/ICSI outcomes when compared with no treatment? A systematic review and meta-analysis.Arch Gynecol Obstet. 2018; 297: 1043-1057Crossref PubMed Scopus (25) Google Scholar). Rapid growth, suspicious features noted on ultrasound, potential for rupture in pregnancy, and inability to access follicles in normal ovarian tissue are also indications for surgery before IVF (35Garcia-Velasco A. Somigliana E. Management of endometrioma in women requiring IVF: to touch or not to touch.Hum Reprod. 2009; 24: 496-501Crossref PubMed Scopus (203) Google Scholar). Surgery must be performed carefully to keep to a minimum any damage to the ovary (by excision or ablative technique). To achieve this, experienced surgeons and an appropriate technique are required. The level of expertise in endometriosis surgery inversely correlates with the amount of ovarian tissue inadvertently removed together with the endometrioma wall (36Muzii L. Marana R. Angioli R. Bianchi A. Cucinella G. Vignali M. et al.Histologic analysis of specimens from laparoscopic endometrioma excision performed by different surgeons: does the surgeon matter?.Fertil Steril. 2011; 95: 2116-2119Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). Indeed, the experience of the surgeon may affect the live birth rate after IVF in women with surgically removed endometriomas (37Yu H.T. Huang H.Y. Soong Y.K. Lee C.L. Chao A. Wang C.J. Laparoscopic ovarian cystectomy of endometriomas: surgeons' experience may affect ovarian reserve and live-born rate in infertile patients with in vitro fertilization intracytoplasmic sperm injection.Eur J Obstet Gynecol Reprod Biol. 2010; 152: 172-175Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar). Looking at the excisional technique (removing of the cyst wall), the ablative technique is defined by the destruction of the cyst wall (using bipolar coagulation, CO2 laser, or plasma energy vaporization). Vaporization allows quick and easy vaporization of the internal wall, with minimal thermal damage to the normal ovarian cortex. A two-step procedure may be used for large endometriomas (more than 5–6 cm in size). Administration of 12 weeks of GnRH analog between the two surgical procedures reduced endometrioma size by up to 50% (38Donnez J. Nisolle M. Gillerot S. Anaf V. Clerckx-Braun F. Casanas-Roux F. Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage.Fertil Steril. 1994; 62: 63-66Abstract Full Text PDF PubMed Google Scholar). A second-look laparoscopy then allows vaporization of the cyst wall (39Tsolakidis D. Pados G. Vavilis D. Athanatos D. Tsalikis T. Giannakou A. et al.The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.Fertil Steril. 2010; 94: 71-77Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 40Pados G. Tsolakidis D. Assimakopoulos E. Athanatos D. Tarlatzis B. Sonographic changes after laparoscopic cystectomy compared with three-stage management in patients with ovarian endometriomas: a prospective randomized study.Hum Reprod. 2010; 25: 672-677Crossref PubMed Scopus (60) Google Scholar). Functional ovarian tissue, as determined by antral follicle counts and antimüllerian hormone levels, was less compromised after the two-step procedure than after cystectomy for endometriomas (40Pados G. Tsolakidis D. Assimakopoulos E. Athanatos D. Tarlatzis B. Sonographic changes after laparoscopic cystectomy compared with three-stage management in patients with ovarian endometriomas: a prospective randomized study.Hum Reprod. 2010; 25: 672-677Crossref PubMed Scopus (60) Google Scholar). The advantages of the two-/three-step technique may also be found in the combined technique, without the inconvenience of two different surgical procedures (41Donnez J. Lousse J.C. Jadoul P. Donnez O. Squifflet J. Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery.Fertil Steril. 2010; 94: 28-32Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). A large part of the endometrioma is first excised according to the cystectomy technique. If the excision provokes bleeding or the plane of cleavage is not clearly visible, the cystectomy is stopped because of the risk of removing healthy ovarian tissue containing follicles and provoking bleeding close to the hilus. The ablative technique is then used to ablate the remaining endometrioma wall close to the hilus. Care must be taken to ablate all the residual cyst wall to avoid recurrence. The combined technique (41Donnez J. Lousse J.C. Jadoul P. Donnez O. Squifflet J. Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery.Fertil Steril. 2010; 94: 28-32Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 42Donnez J. Squifflet J. Donnez O. Minimally invasive gynecologic procedures.Curr Opin Obstet Gynecol. 2011; 23: 289-295Crossref PubMed Scopus (15) Google Scholar) associates the positive effects of both cystectomy and ablation. In a study using this combined technique, vaginal ultrasound revealed a normal antral follicle count and normal ovarian volume 6 months after surgery (41Donnez J. Lousse J.C. Jadoul P. Donnez O. Squifflet J. Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery.Fertil Steril. 2010; 94: 28-32Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). In conclusion, surgery has a fundamental role to play in the treatment of endometriomas. Despite concerns about the effects of this surgery on the ovarian reserve, the benefits in terms of pain relief and spontaneous pregnancy rates favor this approach. However, in cases of recurrent endometriomas or decreased ovarian reserve, the risks of repeated surgery should be considered. Informative randomized controlled trials on the comparison between surgery and IVF for infertile women carrying ovarian endometriomas are lacking, and available guidelines are contradictory (43Hirsch M. Begum M.R. Paniz É. Barker C. Davis C.J. Duffy J. Diagnosis and management of endometriosis: a systematic review of international and national guidelines.Br J Obstet Gynecol. 2018; 125: 556-564Google Scholar). Moreover, from the patient perspective, these two management strategies are extremely different and involve several clinical and personal aspects that are beyond the mere pregnancy rate. One may even wonder whether randomized controlled trials will ever provide a satisfactory answer to the question (44Vercellini P. Somigliana E. Cortinovis I. Bracco B. de Braud L. Dridi D. et al.“You can't always get what you want”: from doctrine to practicability of study designs for clinical investigation in endometriosis.BMC Womens Health. 2015; 15: 89Crossref PubMed Scopus (14) Google Scholar). Therefore, a shared and informed decision with the patient is mandatory, and, to be balanced, this requires in-depth and transparent information in a multidisciplinary context that can offer both surgery and IVF. Two main sets of information should be provided, a general set and a personalized set. The first information set includes realistic information on the effectiveness of the two approaches (an about 25% live birth rate for surgery and a similar 25% live birth rate for a single IVF attempt) (45Vercellini P. Somigliana E. Viganò P. Abbiati A. Barbara G. Crosignani P.G. Surgery for endometriosis-associated infertility: a pragmatic approach.Hum Reprod. 2009; 24: 254-269Crossref PubMed Scopus (188) Google Scholar, 46De Geyter C. Calhaz-Jorge C. Kupka M.S. Wyns C. Mocanu E. Motrenko T. et al.European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE).Hum Reprod. 2018; 33: 1586-1601Crossref PubMed Scopus (272) Google Scholar), their general risks (higher risk of hemorrhage, organ injury, infection, and anesthesia complications for surgery and risk of ovarian hyperstimulation syndrome and multiple pregnancy exclusively for IVF) (47Chapron C. Pierre F. Querleu D. Dubuisson J.B. Complications of laparoscopy in gynecology.Gynecol Obstet Fertil. 2001; 29: 605-612Crossref PubMed Scopus (56) Google Scholar, 48Van Voorhis B.J. Clinical practice. In vitro fertilization.N Engl J Med. 2007; 356: 379-386Crossref PubMed Scopus (121) Google Scholar), their peculiar risks (damage to the ovarian reserve for surgery and endometrioma infection for IVF) (49Somigliana 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: 486-499Crossref PubMed Scopus (64) Google Scholar), and their costs (these vary widely and depend on the local context) (50Chambers G.M. Adamson G.D. Eijkemans M.J. Acceptable cost for the patient and society.Fertil Steril. 2013; 100: 319-327Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). The second information set should be more patient centered and should consider additional factors such as history of previous surgery for endometriosis (favoring IVF) (51Vercellini P. Somigliana E. Viganò P. De Matteis S. Barbara G. Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review.Acta Obstet Gynecol Scand. 2009; 88: 1074-1082Crossref PubMed Scopus (79) Google Scholar, 52Ferrero S. Scala C. Racca A. Calanni L. Remorgida V. Venturini P.L. et al.Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study.Fertil Steril. 2015; 103: 1236-1243Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar), dimension and ultrasound appearance of the endometriomas (larger cysts and doubtful cases favor surgery) (53Ferrero S. Scala C. Tafi E. Racca A. Venturini P.L. Leone Roberti Maggiore U. Impact of large ovarian endometriomas on the response to superovulation for in vitro fertilization: A retrospective study.Eur J Obstet Gynecol Reprod Biol. 2017; 213: 17-21Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 54Guerriero S. Condous G. van den Bosch T. Valentin L. Leone F.P. Van Schoubroeck D. 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: 318-332Crossref PubMed Scopus (306) Google Scholar), bilaterality (favors IVF because of the risk of severe impairment of the ovarian reserve after surgery) (55Somigliana E. Arnoldi M. Benaglia L. Iemmello R. Nicolosi A.E. Ragni G. IVF-ICSI outcome in women operated on for bilateral endometriomas.Hum Reprod. 2008; 23: 1526-1530Crossref PubMed Scopus (131) Google Scholar), concomitant