Urinary Tract Endometriosis: A Review of Literature

Objective: Deep endometriosis (DE) is the most severe form of endometriosis. Bowel and urinary tract are the most common sites of intrapelvic DE. Urinary tract endometriosis (UTE) mainly involves the bladder and the ureters. The two mostly accepted theories explaining the pathophysiology of UTE are the “Retrograde Menstruation Theory” and the “Müllerian Remnants Theory”. The purpose of this paper is to provide a review of literature on the UTE, a rare form, affecting only 1–6% of patients with endometriosis. Mechanism: A literature review was conducted using keywords specific to UTE and DE to identify peer-reviewed, original research articles published between 1996 and 2024. Findings in Brief : When the bladder is involved, the patient presents lower urinary tract symptoms. Ureteral endometriosis is usually asymptomatic, thus delaying early diagnosis and efficient treatment leading to cases of chronic ureteral stricture. Clinical history and examination as well as questionnaires play an important role in guiding the clinician. Diagnostic modalities include conventional imaging such as ultrasonography and magnetic resonance imaging (MRI) as well as invasive techniques such as cystoscopy. As for all endometriotic lesions, definitive diagnosis should be confirmed by histopathology. Treatment modalities include medical hormonal treatments or surgical treatment. There are a multitude of surgical techniques that are more or less invasive depending on the location and the extent of the lesion. Conclusions: UTE, is an underdiagnosed form of endometriosis, and specialists should be aware of this important entity, due to the serious health implications for women.

urinary endometriosis; deep infiltrating endometriosis; urinary symptoms; surgical treatment; medical treatment 1. Introduction Endometriosis is a debilitating gynecological condi- tion characterized by the presence of endometrial-like tis- sue outside the uterus, leading to significant clinical chal- lenges. Although commonly found within the pelvic cavity, endometriosis can also manifest in extrapelvic sites such as the diaphragm [ 1] and more rarely, the umbilical region, inguinal area, and around nerves and organs like the sciatic nerve, liver, and pancreas [2]. The condition can be catego- rized based on lesion localization and depth of infiltration into three types: superficial, ovarian, and deep endometrio- sis (DE) [ 3]. DE, specifically, involves the endometrial- like tissue on or under the peritoneal surface [ 4], with a contentious definition that has been termed adenomyosis externa by Gordts et al . [ 5], characterized by large, often solitary lesions. Urinary tract endometriosis (UTE), a subtype of DE, includes bladder endometriosis (BE) and ureteral en- dometriosis (UE), both associated with severe pelvic pain and significantly impaired quality of life [ 6]. BE is defined by the infiltration of the bladder’s detrusor muscle by en- dometrial glands and stroma, typically multifocal and af- fecting the bladder’s trigone and dome [ 7]. UE involves either direct endometriotic invasion of the ureters or indi- rect compression by associated fibrosis, potentially leading to intrinsic or extrinsic ureteral obstruction [ 8]. Diagnosing UTE poses significant difficulties due to its often-subtle symptoms and the complex nature of its presentation, which can mimic other urological conditions. Standard imaging techniques may fail to detect the extent of the disease or differentiate it from other pelvic pathologies, necessitating more invasive procedures like laparoscopy for definitive diagnosis. Treatment of UTE is equally challeng- ing; it requires a multidisciplinary approach that balances surgical intervention with the preservation of renal function and fertility. Surgical treatment, particularly for ureteral en- dometriosis, involves risks of significant complications and recurrence of the disease. This review will explore the diagnostic complexities and therapeutic challenges in managing UTE, emphasiz- ing the need for improved diagnostic tools and more ef- fective, less invasive treatment options. It will examine the latest advancements in imaging and surgical techniques, and discuss the emerging research on medical management strategies that could offer alternatives to surgery. The re- view aims to highlight critical gaps in current knowledge and suggest directions for future research to enhance patient outcomes in UTE. 2. Epidemiology While endometriosis affects almost one-fifth of repro- ductive aged women, DE prevalence is 1% in reproductive aged women, and 15 to 20% of patients with endometriosis [9]. UTE, a rare entity affecting only 0.3 to 12% of pa- tients with endometriosis [ 8], is more frequent among pa- tients with DE with an incidence of 16.4% to 52.6% [ 10]. UTE mainly involves the bladder (70–85%), the ureters (9– 23%), the kidneys (4%) and the urethra (2%) [11]. The peak age of incidence is 30–35 years. As for all rare diseases, most of the studies consist of small retrospective cohorts and are performed in refer- ral centers leading to a divergence between the published and the real occurrence. The lack of prospective trials and the short term follow up prevent us from establishing stan- dardized diagnosis and therapeutic approaches. BE is usually associated with other forms of pelvic endometriosis (superficial peritoneal, ovarian endometri- omas, adhesions and extravesical DE). UE is rarely isolated; it is associated with ovarian endometriomas in half of the patients with a predilection to the left side [ 12]. Inversely, literature suggests that the presence of rec- tovaginal endometriosis multiplies the risk of developing UE by more than ten if the largest nodule is >3 cm [13]. 3. Methods A literature review was conducted using keywords specific to UTE and DE to identify peer-reviewed, origi- nal research articles published in English between 1996 and 2024. 4. Pathophysiology When DE lesions invade the urinary tract (bladder, ureters or kidneys), it results in UTE. Similarly, to DE, the pathogenesis is still unclear. Non-UTE lesions can also remotely cause UTE like symptoms without an actual in- volvement, this can be caused by an inflammation or an in- filtration of the hypogastric plexus resulting in an involve- ment of sympathetic and parasympathetic lesions [ 14]. The two mostly accepted theories are “Retrograde Menstruation Theory” and “Müllerian Remnants Theory”. “Retrograde Menstruation Theory” suggests a retro- grade flow of endometriotic tissue through the fallopian tubes. The asymmetrical distribution of endometriotic le- sions is a major argument supporting this theory. The fact that most of DE lesions are located in the declivous parts of the pelvis, particularly the involvement of the bladder in UTE, is explained by the gravitational effect on regurgi- tated endometrial tissue and the presence of the recto sig- moid colon. This favors adhesion of sloughed endometrial debris on the left pelvic wall and peritoneum followed by in- flammation and fibrotic nodules formation. Other anatomic observations supporting this theory are the absence of BE in patients with retroverted uterus, and the mode of progres- sion of lesions from the bladder serosa inwards, sparing the mucosal layer most of the time [ 15]. “Müllerian Remnants Theory” or the “Müllerianosis” hypothesis relies on the histology of DE and UTE lesions to hypothesize that DE lesions are in fact adenomyotic lesions secondary to embryonic remnants of the Müllerian ducts and originating in the retroperitoneum. Thus, the presence of fibrotic tissue and smooth muscle cells surrounding the strains of gland and stroma in these lesions [ 16]. This theory may explain the presence of DE without concomitant peritoneal involvement which cannot be ex- plained by the Retrograde Menstruation Theory. Nisolle and Donnez [ 3] in 1997 suggested that DE, peritoneal and ovarian endometriosis are separate entities with different pathogenesis, with the DE presenting more invasive mechanisms. Other theories include the “Hematogenic or Lym- phatic Spread” of specific cell-free endometrial products capable of inducing the metaplasia of undifferentiated mes- enchyme into endometrial epithelium and glands [17]. This can be responsible for distant implants and probably ex- plaining intrinsic UE or isolated DE. The “Iatrogenic The- ory” states that history of pelvic surgery predisposes the dissemination of endometrial cells in the abdominal cavity [17]. “The forgotten menstruation”, according to Brosens et al . [ 18], states that 5% of neonates have neonatal menstruation during the first week after birth which can play a role in the pathogenesis of endometriosis. “The metaplasia theory” was suggested because some women with Mayer–Rokitansky–Küster–Hauser syndrome devel- oped endometriosis. “The genetic and epigenetic theory” since endometriosis is a hereditary disease with the preva- lence increasing from 6 to 15% in first degree relative and depending on the severity of the disease [ 5]. 5. Clinical Presentation In reproductive age patients, the presence of dys- menorrhea, dyspareunia and non-cyclic pelvic pain should evoke DE. Endometriosis rarely involves both the bladder and the ureters. When the bladder is involved, the posterior wall is usually infiltrated [ 19] and the patient typically presents lower urinary tract symptoms (LUTS) such as frequency, dysuria, hematuria, urgency and bladder pain and it is fre- quently misdiagnosed for cystitis [19]. These symptoms are generally cyclic and worsen during menstruation but may as well be constant. As a matter of fact, hematuria is infre- quent because the lesions rarely infiltrate the mucosal layer. Bladder involvement rarely results in severe sequelae espe- cially that this is a very symptomatic entity leading to in- vestigation and early treatment. Ureteral dilation and renal failure could occur only if the ureteral tract is blocked by the endometriotic lesion [ 20]. UE, as well, is usually asymptomatic, thus delaying early diagnosis and efficient treatment. This may lead, in rare cases, to chronic unnoticed ureteral stricture resulting in renal failure or silent kidney loss. When symptomatic, UE causes non-specific symptoms such as dysmenorrhea, pelvic pain, flank pain, gross cyclical hematuria or pelvic mass [21]. 2 Frequently, UTE is diagnosed incidentally during la- paroscopy for extensive endometriosis. 6. Diagnosis 6.1 Clinical History & Examination In patients presenting possible deep endometriotic le- sions, physical examination should include pelvic, abdomi- nal, vaginal and rectal examination. V aginal examination is essential for evaluating patients with DE and especially for detecting BE [ 22]. A palpable nodule or a thickened area along the anterior vaginal wall may be felt and it is painful most of the time. The combined rectovaginal examination helps assessing the parametrial involvement and the palpa- tion of deep infiltrating nodules in the pouch of Douglas or in the uterosacral ligaments associated. Since physical ex- amination in UTE is usually normal, this diagnosis should be evoked if DE nodules are palpated on rectovaginal exam [23]. Differential diagnoses should be considered in pa- tients with suspected UTE. When patients present lower uri- nary tract symptoms, the physician should consider BE but should also rule out infectious or interstitial cystitis, over- active bladder, bladder carcinoma, bladder pain syndrome and chronic urethral syndrome [24]. When UE is suspected, the physician should also consider other causes or intrin- sic or extrinsic ureteral stenosis such as stones, primary or metastatic neoplastic lesions, retroperitoneal adenopathy, idiopathic retroperitoneal fibrosis and infection [21]. Imag- ing techniques should be used to rule out these entities. 6.2 Questionnaires The modified American Urologic Association Symp- tom Index (AUASI) questionnaire is a 7-itemed question- naire developed in 2007 to evaluate specific catamenial symptoms, and was proven effective in identifying patient with BE [25]. The Bristol Female LUTS is another questionnaire validated in assessing the variety of LUTS symptoms asso- ciated with DE and UTE, as well as the follow up of patients after treatment. It is made of 3 domains: symptoms, sexual function and quality of life questions [ 26]. 6.3 Imaging 6.3.1 Ultrasonography Ultrasonography, a non-invasive, cost effective and reproducible diagnostic tool is recommended for systematic use in assessing women with DE [ 27]. In BE, it evaluates the location and size of lesions and measures the distance between the lesion and the ureteral orifices. When the blad- der is full, endometriotic lesions appear as filling defects of the posterior wall with a variable protrusion into the lu- men of the bladder. Bladder lesions are usually spherical, or comma shaped with regular contours. When contours are irregular, malignancy should be ruled out. Barra et al. [28], detected nodules with a mean diameter of 20 mm ± 9.1 mm. On colored Doppler, bladder endometriotic lesions present minimal to moderate internal blood flow. Abdom- inal ultrasonography does not visualize the entire ureteral course, making it impossible to directly detect ureteral en- dometriotic lesions, but it can evaluate the presence and the severity of hydronephrosis thus indirectly diagnosing UE and obstruction [29]. Both abdominal and transvaginal ultrasound (TVUS) may be used to detect vesical endometriotic lesions, with TVUS being the preferred method and should be used as first-line. During ureteral dilation assessment, the location of the stenosis and its distance from the bladder should be evalu- ated as well as the ureteral diameter upstream and down- stream the obstruction [ 21]. A ureteral diameter of ≥6 mm was associated with ureteral dilation [ 30]. With color Doppler, TVUS was found superior to cys- toscopy in detecting BE nodules partially affecting the de- trusor muscle [ 31] and at least as effective as the magnetic resonance imaging (MRI) in diagnosing and planning the treatment of BE. It is suggested that it may improve the as- sessment of endometriotic nodules, their sizes, volume and infiltration of the bladder wall [32]. Color Doppler can also help to evaluate Relative Jet Frequency which can be a good indicator of obstruction if reduced ( <25%) [33]. Intraluminal ultrasonography is an invasive exam currently under evaluation, consisting of introducing a catheter-based ultrasound probe in the ureters, to assess the ureteral lumen, wall and peri-ureteral tissues [ 21]. 6.3.2 Magnetic Resonance Imaging MRI is the second-line imaging technique used for the evaluation of UTE. In BE assessment, it offers a higher res- olution, better delineation of the bladder wall layers, better tissue characterization and better multiplanar analysis when compared to non-3D ultrasonography [ 34]. In MRI, BE lesions may manifest as localized or dif- fuse wall thickening associated with signal intensity abnor- malities. Typical features are low signal on T2 weighted im- ages with intermediated signal on T1 weighted images and spots of high signal on T1 and T2 weighted images repre- senting hemorrhagic content. Systematic reviews showed no advantage for 3.0-T MRI or for Gadolinium-enhanced imaging. MRI reaches an 88% sensitivity and 99% speci- ficity and 98% diagnostic accuracy for BE diagnosis [ 20]. It is the best imaging for UE assessment; lesions ap- pear as solid nodules with spiculated margins surrounding the ureter and showing low intensity signal on T1 and T2 weighted images. Concurrent retractile adhesions appear as peri-ureteral hypo-intense linear foci with angular devia- tion. In cases of extrinsic endometriosis, the loss of fatty in- terface between the nodule and the ureter suggests ureteral infiltration. MRI showed to be more sensitive but less spe- cific than laparoscopy in identifying intrinsic ureteral in- volvement [35]. 3 A new pre-operative (MRI, TVUS) classification, #ENZIAN, can be used to describe DE lesions including UE [36]. Since MRI is more expensive but not superior to TVUS performed by experienced physicians, it should not be used as a first line diagnostic tool [ 34]. 6.3.3 Other Imaging Intravenous and retrograde pyelography were tradi- tionally used to evaluate women with suspected UTE but have been replaced with MRI [ 37]. Renal scintigraphy should be performed in cases of se- vere hydronephrosis to assess the renal function and plan surgical treatment in association to nephrectomy or kidney preservation. A kidney is considered salvageable if preop- erative glomerular filtration rate is more than 10%. 6.3.4 Cystoscopy It is commonly performed in the outpatient setting to assess the urethra, bladder inner wall and ureteral orifices. Even in the presence of BE, cystoscopy findings are usu- ally normal due to the sparing of the mucosal layer [ 24]. The lesions may appear as adenomatous nodular masses with varying shades of colors (red, blue, brown or black) [38]. Cystoscopy should be planned immediately before or during menstruation to best visualize the nodules when they are enlarged and congested. It helps planning the surgery by estimation of the distance between the nodules and the ureteral openings [ 7], especially when no feasible with TVUS, should also be used to rule out malignancy [24]. 6.3.5 Urodynamics Data in the literature evaluating the role of urodynam- ics in assessing patients with UTE and DE is very scarce. Patients present typically higher bladder sensation, painful bladder filling, voiding symptoms, urgency, frequency and bladder pain. Its use is not recommended in clinical prac- tice and is currently limited to scientific research purposes [39]. 7. Histology As for all endometriotic lesions, definitive diagnosis is confirmed by histopathology. In contrast with surgery, histology can precisely assess the depth of invasion. The two main pathological subtypes are extrinsic and intrinsic endometriosis. Extrinsic endometriosis only invades the ureteral adventitia or surrounding connective tissue, while intrinsic endometriosis directly infiltrates the muscularis, submucosa and rarely the mucosal layer. The two subtypes can sometimes coexist [ 40]. When evaluating UE, two patterns were described: an endometriotic pattern corresponding to endometrial glands or stromal cells seen in the wall of the ureters or in the peri- ureteral space and a fibrotic pattern made of fibrotic tissue only [41]. The endometriotic pattern is more prevalent and as- sociated with the presence of ureteral obstruction and hy- dronephrosis. The fibrotic pattern is associated with the rectovaginal nodules which might be related to the inflam- matory process caused by a DE close to the ureters [ 3,41]. 8. Treatment DE involves mainly the posterior compartment of the pelvis and is frequently associated to UTE and causes LUTS. Treatment modalities for DE/UTE include medical and surgical treatments. Medical treatment can be cho- sen for asymptomatic women without hydronephrosis. Per- sisting symptoms along with ureteral obstruction and hy- dronephrosis require surgery. Compared to minimally inva- sive surgery (MIS), laparotomy is associated with poorer vi- sualization of small infiltrating lesions resulting in larger in- cisions, increased blood loss, increased post-operative pain and recovery time. Laparoscopic management of severe ex- tra genital endometriosis was published in the 1980s. Sur- gical treatment of UTE is still not very common due to its underdiagnoses and failure to identify endometriotic lesions by unexperienced surgeons. Furthermore, most of the gen- eral, urology and gynecology surgeons are not trained to treat DE. 8.1 Medical/Hormonal Treatment Combined hormonal contraceptives and progestogens are the first line therapies for patients with DE and UTE and have proven efficacious in the treatment of different DE including UTE [42]. Recent data suggest that symptoms and lesions may not respond completely to medical therapies because of the desmoplastic reaction within the tissues resulting from repetitive bleeding and resorption of menstrual debris [ 43]. Gonadotropin-releasing hormone agonists (GnRH- as): leuprolide acetate and danazol are second line ther- apy because of the hypoestrogenism related adverse effects ranging from hot flashes, sleep disturbances, irregular vagi- nal bleeding, weight gain and vaginal dryness. Further- more, once the treatment is discontinued, symptoms tend to recur [44]. Aromatase Inhibitors can be prescribed to patients re- fractory to conventional therapies in the setting of clinical research [45]. Women treated medically must undergo regular clini- cal examination, ultrasonography and laboratory testing to monitor renal function, disease progression, and necessity for surgery [24]. Medical treatment is contraindicated in patients with ureteral obstruction because of the risk of disease progres- sion and increased severity of ureteral stricture and hy- dronephrosis, thus surgery is the standard approach for mild to severe UE. However, post-operative medical treatment may be useful in preventing recurrence of endometriosis 4 [21]. 8.2 Surgical Treatment The aim of surgical treatment is to entirely resect the UTE lesions, relieve related symptoms, ureteral obstruc- tion, preserve renal function and avoid recurrence. The sur- gical approach should be tailored to the extent of the dis- ease, the renal function and the surgeon’s skills, thus the major importance of preoperative accurate mapping of all lesions and their distance to the ureteral meatuses [ 46]. MIS remains the recommended approach because la- paroscopy has demonstrated its superiority to laparotomy for treating UE [ 21]. During surgery for UTE, identification of the ureters is essential to avoid iatrogenic injury and to evaluate for pos- sible ureteral involvement [ 29]. Surgical options for BE include trans urethral resection (TUR) and partial cystec- tomy [ 24]. For UE, surgical options include conservative ureterolysis and radical approaches such as ureterectomy with an end-to-end anastomosis, ureteroneocystostomy or nephroureterectomy. Conservative treatments like ureterolysis should be limited to patients with minimal ureteral involvement. When ureteral endometriosis does not cause stenosis and hydronephrosis, ureterolysis with or without ureteral shav- ing may be considered. The indication for ureteroneo- cystostomy should be the presence of moderate/severe hy- dronephrosis due to ureteral obstruction. The risk of conservative treatment is mainly steno- sis with a risk up to 12 to 20% of patients who underwent ureteroureterostomy and ureterolysis, respectively [ 12]. 8.2.1 TUR Surgery TUR is a proposed technique to treat BE without enough evidence supporting its efficacy or safety. Since BE develop from the bladder serosa inwards, complete ex- cision of endometriotic lesions is impossible by trans ure- thral resection without exposing the patient to increased risk of bladder perforation or short-term recurrence in case of incomplete resection [47]. 8.2.2 Segmental Bladder Resection Partial cystectomy is a bladder conserving option proven effective with excellent long-term results in control- ling symptoms and lowering the risk of recurrence. It con- sists of partial bladder resection for detrusor endometriosis performed via laparotomy or MIS with or without robotic assistance. Suturing the bladder defect can be performed in 1 or 2 layers, continuous or interrupted sutures [ 19]. Ureter catheterization is not systematic and depends on the distance between the caudal margin of the lesion and the inter-ureteric ridge; if the distance is less than 2 cm, catheterization is advisable. But in case of recurrent en- dometriosis, lesions tend to be closer to the ureteral mea- tuses, thus catheterization is mandatory. This surgery is considered as simple and safe with fast healing of bladder sutures and low risk of vesical fistula if prolonged drainage is performed [ 46]. Some surgeons combine the TUR surgery with the segmental bladder resection to overcome the limitations of both techniques by allowing complete resection of the nod- ule (contrary to the TUR) without any accidental excision of healthy tissue [ 48]. 8.2.3 Ureterolysis Safe and efficient, it aims to mobilize and free the ureter from the surrounding endometriosis and fibrosis. It is indicated in patients presenting minimal extrinsic non- obstructive UE, but it is also performed in cases of mild to severe obstruction in order to clearly visualize the stenotic area [13]. Intra-urethral injection of near infra-red Indocyanine Green improves the visualization of ureters, therefore pre- venting iatrogenic injuries [ 49]. Moreover, it helps assess ureteral perfusion after conservative surgery. 8.2.4 Endoscopic Excision Retrograde ureteroscopy is a minimally invasive pro- cedure allowing effective excision in cases of polypoid en- dometriotic lesions obstructing the ureteral lumen. It is not efficient for patients presenting deep ureteral wall fibrosis and periureteral connective tissue fibrosis [ 50]. 8.2.5 Ureteral Stenting Literature shows that the risk of ureteral injury dur- ing laparoscopic surgery is 1.5% for patients having UE versus 21% for patients presenting hydronephrosis [ 51]. Ureteral stenting serves mainly to release the obstruction, improve renal function, facilitate ureteral identification, guide ureterolysis and prevent ureteral injury as well as pre- venting postoperative ureteral obstruction due to the local inflammation and edema. 8.2.6 Partial Ureteral Wall Resection Described by Nezhat et al. [ 52] and Ghezzi et al. [ 53] in 1996 and 2007, respectively with no major complications reported. But this technique should undergo further evalu- ation [52]. 8.2.7 Ureteral Resection with End to End Anastomosis This technique allows complete excision of the in- volved segment of the ureter and its surrounding fibrosis. Anastomotic breakdown or anastomotic stricture are the most described complications. By preserving the distal part of the ureter and the vesico-ureteral junction, patients are at a higher risk of recurrent endometriosis [ 54]. This tech- nique is indicated in patients presenting severe segmental ureteral obstruction limited to the middle or upper parts of the ureter. 5 8.2.8 Uretero-Neocystotomy This technique is indicated for cases of extensive ureteral involvement, lesions close to the bladder insertion and lesions extending over a long pelvic ureteral segment making ureterolysis and end to end anastomosis impossi- ble. It consists of excision and reimplantation of the ureter into the bladder, bypassing the endometriotic zone and its surrounding fibrosis. Depending on the length of the re- sected area, a psoas bladder hitch or a Boari flap may be required to insure tension free anastomosis [ 14]. Literature shows a significant improvement of the symptoms with this procedure, a low rate of recurrence at 24 months (1.2%) and a low rate of major complications (4.4%) [21]. 8.2.9 Nephrectomy Chronic gradual ureteral stenosis can ultimately lead to loss of renal function and eventually silent kidney loss (End Stage Renal Disease). This can be evaluated by kidney scintigraphy in patients presenting UE related hydronephro- sis [ 13]. Nephrectomy is indicated in patients with renal functions less than 15%, suffering from flank pain, kid- ney stones, renovascular hypertension and recurrent urinary tract infection or pyelonephritis [ 55]. 9. Conclusions UTE is rare but frequently documented in the context of DE. Careful preoperative planning should be scheduled to diagnose an advanced-stage disease defining the depth, severity and site of these lesions. Medical management could be proposed in a subset of patients, however, the minimally invasive surgical treat- ment remains associated with a long-term optimal outcome. Author Contributions HEH: Data collection, manuscript writing. RS: Data collection, manuscript editing. EF: Interpretation of Data, manuscript editing. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. Ethics Approval and Consent to Participate Not applicable. Acknowledgment We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions. Funding This research received no external funding. Conflict of Interest The authors declare no conflict of interest.

[1] Andres MP , Arcoverde FVL, Souza CCC, Fernandes LFC, Abrão MS, Kho RM. Extrapelvic Endometriosis: A Systematic Review. Journal of Minimally Invasive Gynecology. 2020; 27: 373–389. [2] Fedele F, Di Fatta S, Busnelli A, Bulfoni A, Salvatore S, Candi- ani M. Rare extragenital endometriosis: pathogenesis and ther- apy. Clinical and Experimental Obstetrics & Gynecology. 2022; 49: 43. [3] Nisolle M, Donnez J. Peritoneal endometriosis, ovarian en- dometriosis, and adenomyotic nodules of the rectovaginal sep- tum are three different entities. Fertility and Sterility. 1997; 68: 585–596. [4] International working group of AAGL, ESGE, ESHRE and WES, Tomassetti C, Johnson NP , Petrozza J, Abrao MS, Einars- son JI, et al . An International Terminology for Endometriosis, 2021. Journal of Minimally Invasive Gynecology. 2021; 28: 1849–1859. [5] Gordts S, Koninckx P , Brosens I. Pathogenesis of deep en- dometriosis. Fertility and Sterility. 2017; 108: 872–885.e1. [6] V eeraswamy A, Lewis M, Mann A, Kotikela S, Hajhosseini B, Nezhat C. Extragenital endometriosis. Clinical Obstetrics and Gynecology. 2010; 53: 449–466. [7] V ercellini P , Meschia M, De Giorgi O, Panazza S, Cortesi I, Crosignani PG. Bladder detrusor endometriosis: clinical and pathogenetic implications. The Journal of Urology. 1996; 155: 84–86. [8] Gennaro KH, Gordetsky J, Rais-Bahrami S, Selph JP . Ureteral Endometriosis: Preoperative Risk Factors Predicting Extensive Urologic Surgical Intervention. Urology. 2017; 100: 228–233. [9] Koninckx PR, Ussia A, Keckstein J, Wattiez A, Adamyan L. Epi- demiology of subtle, typical, cystic, and deep endometriosis: a systematic review. Gynecology Surgery. 2016; 13: 457–467. [10] Abrao MS, Dias JA, Jr, Bellelis P , Podgaec S, Bautzer CR, Gro- matsky C. Endometriosis of the ureter and bladder are not asso- ciated diseases. Fertility and Sterility. 2009; 91: 1662–1667. [11] Saavalainen L, Heikinheimo O, Tiitinen A, Härkki P . Deep infiltrating endometriosis affecting the urinary tract-surgical treatment and fertility outcomes in 2004-2013. Gynecological Surgery. 2016; 13: 435–444. [12] Ceccaroni M, Ceccarello M, Caleffi G, Clarizia R, Scarperi S, Pastorello M, et al . Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients. Journal of Minimally Invasive Gynecol- ogy. 2019; 26: 78–86. [13] Donnez J, Nisolle M, Squifflet J. Ureteral endometriosis: a com- plication of rectovaginal endometriotic (adenomyotic) nodules. Fertility and Sterility. 2002; 77: 32–37. [14] Nezhat C, Falik R, McKinney S, King LP . Pathophysiology and management of urinary tract endometriosis. Nature Reviews. Urology. 2017; 14: 359–372. [15] Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. American Journal of Obstetrics and Gynecology. 1927; 14: 422– 469. [16] Batt RE, Y eh J. Müllerianosis: four developmental (embryonic) mullerian diseases. Reproductive Sciences. 2013; 20: 1030– 1037. [17] Laganà AS, Garzon S, Götte M, Viganò P , Franchi M, Ghezzi F, et al. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. International Journal of Molecular Sciences. 2019; 20: 5615. 6 [18] Brosens I, Benagiano G. Is neonatal uterine bleeding involved in the pathogenesis of endometriosis as a source of stem cells? Fertility and Sterility. 2013; 100: 622–623. [19] Tomasi M, Ribeiro PA, Farah D, Cervantes G, Nicola A De, Abdalla-Ribeiro H. Symptoms and Surgical Technique of Blad- der Endometriosis: A Systematic Review. Journal of Minimally Invasive Gynecology. 2022; 29: 1294–1302. [20] Maccagnano C, Pellucchi F, Rocchini L, Ghezzi M, Scattoni V , Montorsi F, et al . Diagnosis and treatment of bladder en- dometriosis: state of the art. Urologia Internationalis. 2012; 89: 249–258. [21] Barra F, Scala C, Biscaldi E, V ellone VG, Ceccaroni M, Ter- rone C, et al . Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malig- nant transformation and fertility. Human Reproduction Update. 2018; 24: 710–730. [22] Bazot M, Daraï E. Diagnosis of deep endometriosis: clinical ex- amination, ultrasonography, magnetic resonance imaging, and other techniques. Fertility and Sterility. 2017; 108: 886–894. [23] Riazi H, Tehranian N, Ziaei S, Mohammadi E, Hajizadeh E, Montazeri A. Clinical diagnosis of pelvic endometriosis: a scop- ing review. BMC Women’s Health. 2015; 15: 39. [24] Leone Roberti Maggiore U, Ferrero S, Candiani M, Somigliana E, Viganò P , V ercellini P . Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fer- tility, and Risk of Malignant Transformation. European Urology. 2017; 71: 790–807. [25] Fedele L, Bianchi S, Carmignani L, Berlanda N, Fontana E, Frontino G. Evaluation of a new questionnaire for the presur- gical diagnosis of bladder endometriosis. Human Reproduction (Oxford, England). 2007; 22: 2698–2701. [26] Jackson S, Donovan J, Brookes S, Eckford S, Swithinbank L, Abrams P . The Bristol Female Lower Urinary Tract Symptoms questionnaire: development and psychometric testing. British Journal of Urology. 1996; 77: 805–812. [27] Menakaya U, Reid S, Infante F, Condous G. Systematic eval- uation of women with suspected endometriosis using a 5- domain sonographically based approach. Journal of Ultrasound in Medicine. 2015; 34: 937–947. [28] Barra F, Alessandri F, Scala C, Ferrero S. Ultrasonographic 3D Evaluation in the Diagnosis of Bladder Endometriosis: A Prospective Comparative Diagnostic Accuracy Study. Gyneco- logic and Obstetric Investigation. 2021; 86: 299–306. [29] 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. Fertility and Sterility. 2010; 93: 2115–2120. [30] Carfagna P , De Cicco Nardone C, De Cicco Nardone A, Testa AC, Scambia G, Marana R, et al . Role of transvaginal ultra- sound in evaluation of ureteral involvement in deep infiltrating endometriosis. Ultrasound in Obstetrics & Gynecology. 2018; 51: 550–555. [31] Ros C, de Guirior C, Rius M, Escura S, Martínez-Zamora MÁ, Gracia M, et al. Accuracy of Transvaginal Ultrasound Compared to Cystoscopy in the Diagnosis of Bladder Endometriosis Nod- ules. Journal of Ultrasound in Medicine. 2021; 40: 1571–1578. [32] Thonnon C, Philip CA, Fassi-Fehri H, Bisch C, Coulon A, de Saint-Hilaire P ,et al. Three-dimensional ultrasound in the man- agement of bladder endometriosis. Journal of Minimally Inva- sive Gynecology. 2015; 22: 403–409. [33] de Bessa J, Jr, Dénes FT, Chammas MC, Cerri L, Monteiro EDS, Buchpiguel CA, et al . Diagnostic accuracy of color Doppler sonographic study of the ureteric jets in evaluation of hy- dronephrosis. Journal of Pediatric Urology. 2008; 4: 113–117. [34] Schneider C, Oehmke F, Tinneberg HR, Krombach GA. MRI technique for the preoperative evaluation of deep infiltrating en- dometriosis: current status and protocol recommendation. Clin- ical Radiology. 2016; 71: 179–194. [35] Balleyguier C, Roupret M, Nguyen T, Kinkel K, Helenon O, Chapron C. Ureteral endometriosis: the role of magnetic res- onance imaging. The Journal of the American Association of Gynecologic Laparoscopists. 2004; 11: 530–536. [36] Keckstein J, Saridogan E, Ulrich UA, Sillem M, Oppelt P , Schweppe KW, et al . The #Enzian classification: A compre- hensive non-invasive and surgical description system for en- dometriosis. Acta Obstetricia et Gynecologica Scandinavica. 2021; 100: 1165–1175. [37] Biscaldi E, Barra F, Leone Roberti Maggiore U, Ferrero S. Other imaging techniques: Double-contrast barium enema, en- doscopic ultrasonography, multidetector CT enema, and com- puted tomography colonoscopy. Best Practice & Research. Clin- ical Obstetrics & Gynaecology. 2021; 71: 64–77. [38] Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertility and Sterility. 2012; 98: 511–519. [39] Ballester M, Dubernard G, Wafo E, Bellon L, Amarenco G, Bel- ghiti J, et al. Evaluation of urinary dysfunction by urodynamic tests, electromyography and quality of life questionnaire before and after surgery for deep infiltrating endometriosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2014; 179: 135–140. [40] Y ohannes P . Ureteral endometriosis. The Journal of Urology. 2003; 170: 20–25. [41] Seracchioli R, Raimondo D, Di Donato N, Leonardi D, Spagnolo E, Paradisi R, et al. Histological evaluation of ureteral involve- ment in women with deep infiltrating endometriosis: analysis of a large series. Human Reproduction. 2015; 30: 833–839. [42] V ercellini P , Buggio L, Berlanda N, Barbara G, Somigliana E, Bosari S. Estrogen-progestins and progestins for the manage- ment of endometriosis. Fertility and Sterility. 2016; 106: 1552– 1571.e2. [43] Noël JC, Chapron C, Bucella D, Buxant F, Peny MO, Fayt I, et al. Estrogen and progesterone receptors in smooth muscle com- ponent of deep infiltrating endometriosis. Fertility and Sterility. 2010; 93: 1774–1777. [44] Rafique S, Decherney AH. Medical Management of En- dometriosis. Clinical Obstetrics and Gynecology. 2017; 60: 485–496. [45] Ferrero S, Remorgida V , Maganza C, V enturini PL, Salvatore S, Papaleo E, et al. Aromatase and endometriosis: estrogens play a role. Annals of the New Y ork Academy of Sciences. 2014; 1317: 17–23. [46] Working group of ESGE, ESHRE, and WES, Keckstein J, Becker CM, Canis M, Feki A, Grimbizis GF, et al . Recom- mendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. Human Reproduction Open. 2020; 2020: hoaa002. [47] Fedele L, Bianchi S, Zanconato G, Bergamini V , Berlanda N, Carmignani L. Long-term follow-up after conservative surgery for bladder endometriosis. Fertility and Sterility. 2005; 83: 1729–1733. [48] Roman H, Arambage K, Pasquier G, Resch B, Huet E. Com- bined cystoscopic and laparoscopic approach in deep en- dometriosis of the bladder. Journal of Minimally Invasive Gy- necology. 2014; 21: 978–979. [49] Mandovra P , Kalikar V , Patankar RV . Real-Time Visualization of Ureters Using Indocyanine Green During Laparoscopic Surg- eries: Can We Make Surgery Safer? Surgical Innovation. 2019; 26: 464–468. [50] Castaneda CV , Shapiro EY , Ahn JJ, V an Batavia JP , Silva MV , Tan Y ,et al . Endoscopic management of intraluminal ureteral endometriosis. Urology. 2013; 82: 307–312. 7 [51] De Cicco C, Schonman R, Craessaerts M, V an Cleynenbreugel B, Ussia A, Koninckx PR. Laparoscopic management of ureteral lesions in gynecology. Fertility and Sterility. 2009; 92: 1424– 1427. [52] Nezhat C, Nezhat F, Nezhat CH, Nasserbakht F, Rosati M, Sei- dman DS. Urinary tract endometriosis treated by laparoscopy. Fertility and Sterility. 1996; 66: 920–924. [53] Ghezzi F, Cromi A, Bergamini V , Bolis P . Management of ureteral endometriosis: areas of controversy. Current Opinion in Obstetrics and Gynecology. 2007; 19: 319–324. [54] Freire MJ, Dinis PJ, Medeiros R, Sousa L, Águas F, Figueiredo A. Deep Infiltrating Endometriosis-Urinary Tract Involvement and Predictive Factors for Major Surgery. Urology. 2017; 108: 65–70. [55] Nezhat C, Paka C, Gomaa M, Schipper E. Silent loss of kidney seconary to ureteral endometriosis. JSLS: Journal of the Society of Laparoendoscopic Surgeons. 2012; 16: 451–455. 8