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This narrative review aims to summarize available evidence on the IVF-associated outcomes after surgery for endometriosis. Only one retrospective study investigated if surgical treatment of superficial/peritoneal endometriosis may modify the outcomes of IVF; therefore, more data are needed to confirm the benefit of surgery for this type of disease for improving ART outcomes, and to be able to support it in routine practice. Solid evidence from several meta-analyses demonstrates that surgical treatment of endometriomas does not enhance the outcomes of IVF. In contrast, surgical treatment of ovarian endometriosis may lead to a reduction in ovarian reserve, especially in cases involving bilateral endometriomas or repeated surgical procedures. Some non-randomized studies have examined if surgical treatment on deep endometriosis may influence IVF outcomes. A systematic review with meta-analysis revealed that patients who underwent surgery before IVF exhibited significantly higher pregnancy rates per patient, pregnancy rates per cycle, and live birth rates per patient compared to those without prior surgery. However, the available data are insufficient to recommend surgical excision of deep endometriosis as the first-line treatment for asymptomatic patients to enhance IVF outcomes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In recent years, advancements in cryopreservation techniques for oocytes, embryos, and ovarian tissue have enabled offering fertility preservation (FP) options to women with endometriosis. It is recommended to always conduct specialized counselling on FP, especially before considering surgical interventions for endometriosis. The decision regarding the methods of FP, the timing, and to which women affected by endometriosis these techniques should be offered are still subjects of discussion. However, several studies suggest that it can be proposed before surgical interventions for endometriosis, particularly if the patient is undergoing mono or bilateral endometrioma surgery. The most recommended technique is ovarian stimulation, followed by oocyte cryopreservation. Nevertheless, the literature contains various studies describing FP through embryo cryopreservation or the retrieval and cryopreservation of ovarian tissue., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To study the ultrasonographic diagnostic accuracy and characteristics of parametrial endometriosis comprehensively., Design: This prospective study enrolled patients with suspected deep endometriosis (DE) scheduled for laparoscopic surgical treatment. Preoperative ultrasonographic examinations were performed following the International Deep Endometriosis Analysis criteria. This study aimed to evaluate the presence of parametrial endometriosis and its ultrasonographic characteristics, using surgical diagnosis as the reference standard. Additionally, indirect signs of DE and concomitant DE nodules associated with parametrial involvement were identified, assessing their predictive significance in the anterior, lateral, and posterior parametrial areas., Setting: Referral institution for endometriosis., Patients: Patients with suspected DE scheduled for surgical treatment., Interventions: Standardized preoperative ultrasonographic examination., Main Outcome Measures: The diagnostic accuracy of transvaginal ultrasound in identifying parametrial endometriosis, including sensitivity and specificity, and the ultrasonographic characteristics of parametrial nodules, prevalence in distinct parametrial areas, and associations with indirect DE signs and concomitant DE nodules., Results: Surgical confirmation of parametrial nodules was observed in 105 of 545 patients (left, 18.5; right, 17.0%). Transvaginal ultrasound demonstrated a sensitivity of 77.1% (95% confidence interval, 68.0%-84.8%) and specificity of 99.1% (95% confidence interval, 67.7%-99.8%). Parametrial nodules typically exhibited characteristics such as a mild hypoechoic appearance (83.6%), starry morphology (74.7%), irregular margins (70.2%), and low vascularization. The posterior parametrial region was the most common location (52.2%), followed by the lateral (41.0%) and anterior (6.8%) parametrial regions. Concomitant DE nodules in the rectum (63.5%) and infiltrating the rectovaginal septum (56.5%) were significantly more prevalent in patients with parametrial involvement. Indirect DE signs, such as the ovaries fixed to the uterine wall (71.8%) and the absence of a posterior sliding sign (51.8%), were also more common in women with parametrial nodules. Hydronephrosis, although relatively uncommon in patients with parametrial involvement (8.2%), was largely detected in lateral parametrial nodules (70.0%)., Conclusions: This study represents a systematic ultrasonographic characterization of parametrial endometriosis. Specifically, it comprehensively assesses the diagnostic accuracy of transvaginal ultrasound in identifying parametrial involvement within a sizable cohort of patients with preoperative suspicion of DE., Clinical Trial Registration Number: NCT06017531., Competing Interests: Declaration of Interests F.B. has nothing to disclose. C.Z. has nothing to disclose. M.A. has nothing to disclose. P.D.M. has nothing to disclose. A.S. has nothing to disclose. G.R. has nothing to disclose. M.G. has nothing to disclose. G.A. has nothing to disclose. S.F. has nothing to disclose. M.C. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients., Methods: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test., Results: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001)., Conclusions: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Deep endometriosis (DE) can be localized in the parametrium, a complex bilateral anatomical structure, sometimes necessitating intricate surgical intervention due to the potential involvement of autonomic nerves, uterine artery, and ureter. If endometriotic ovarian cysts have been considered metaphorically representative of "the tip of the iceberg" concerning concealed DE lesions, it is reasonable to assert that parametrial lesions should be construed as the most profound region of this iceberg. Also, based on a subdual clinical presentation, a comprehensive diagnostic parametrial evaluation becomes imperative to strategize optimal management for patients with suspected DE. Recently, the ULTRAPARAMETRENDO studies aimed to evaluate the role of transvaginal ultrasound for parametrial endometriosis, showing distinctive features, such as a mild hypoechoic appearance, starry morphology, irregular margins, and limited vascularization. The impact of medical therapy on parametrial lesions has not been described in the current literature, primarily due to the lack of adequate detection at imaging. The extension of DE into the parametrium poses significant challenges during the surgical approach, thereby increasing the risk of intra- and postoperative complications, mainly if performed by centers with low expertise and following multiple surgical procedures where parametrial involvement has gone unrecognized. Over time, the principles of nerve-sparing surgery have been incorporated into the surgical DE treatment to minimize iatrogenic damage and potentially reduce the risk of functional complications., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endometriosis is a benign, chronic, inflammatory condition affecting up to 10 % of women and characterised by the presence of glands and stroma tissue outside the uterus. Epidemiological and clinical studies demonstrate a consistent association between endometriosis and infertility. However, this relationship is far to be clearly understood and several mechanisms are involved. Available data show that patients with endometriosis have an increased estimated risk of infertility between two and four times compared with the general population. On the other hand, the probability of patients with infertility to have endometriosis is reported up to about 50 % of the cases. Future studies should aim to better elucidate the mechanisms behind endometriosis-associated infertility in order to offer the more appropriate and tailored management for the patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As endometriosis is recognized as a contributing factor to infertility, prompting couples to embark on Assisted Reproductive Technology (ART) treatments, it becomes crucial to comprehend the extent and way this condition can affect success rates. Natural conception data reveal lower success rates for women with endometriosis, yet the same cannot be extrapolated to the outcomes of in vitro fertilization (IVF). In recent years, advancements in the ART process, particularly the distinct stages of the IVF pathway and investigations into embryo quality have shown a comparable rate of embryonic quality and chromosomal normalcy (euploidy) between embryos obtained from individuals with or without endometriosis. Thus, the primary question that lingers relates to the functionality of the endometrium. This review addresses whether endometriosis can influence endometrial receptivity and implantation rates., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy., Areas Covered: The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis., Expert Opinion: Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.

Endometriosis is a painful gynecological disease with a high prevalence, affecting millions of women worldwide. Innovative, non-invasive treatments, and new patient follow-up strategies are needed to deal with the harmful social and economic effects. In this scenario, considering the recent, very promising results already reported in the literature, a commitment to new research in the field of nanomedicine is urgently needed. Study findings clearly show the potential of this approach in both the diagnostic and therapeutic phases of endometriosis. Here, we offer a brief review of the recent exciting and effective applications of nanomedicine in both the diagnosis and therapy of endometriosis. Special emphasis will be placed on the emerging theranostic application of nanoproducts, and the combination of phototherapy and nanotechnology as new therapeutic modalities for endometriosis. The review will also provide interested readers with a guide to the selection process and parameters to consider when designing research into this type of approach.

Study Objective: To evaluate ultrasonographic findings as a first-line imaging tool to indirectly predict the presence of parametrial endometriosis (PE) in women with suspected deep endometriosis (DE) undergoing surgery., Design: Retrospective analysis of a prospectively collected database (ULTRA-PARAMETRENDO I study; NCT05239871)., Setting: Referral center for DE., Patients: Consecutive patients undergoing laparoscopic surgery for DE., Interventions: Preoperative transvaginal ultrasonography was done according to the International Deep Endometriosis Analysis consensus statement. A stepwise forward regression analysis was performed considering the simultaneous presence of DE nodules and the following ultrasonographic indirect signs of DE: diffuse adenomyosis, endometriomas, ovary fixed to the lateral pelvic wall or the uterine wall, absence of anterior/posterior sliding sign, and hydronephrosis. The gold standard for the presence of PE was surgery with histologic confirmation., Measurements and Main Results: Of 1079 patients, 212 had a surgical diagnosis of PE (left: 18.5%; right: 17.0%; bilateral: 15.9%). The obtained prediction model (χ 2  = 222.530; p <.001) for PE included, as independent indirect DE signs presence of hydronephrosis (odds ratio [OR] = 14.5; p = .002), complete absence of posterior sliding sign (OR = 3.3; p <.001), presence of multiple endometriomas per ovary (OR = 3.0; p = .001), and ovary fixation to the uterine wall (OR = 2.4; p <.001); as independent concomitant DE nodules, presence of uterosacral nodules with the largest diameter >10 mm (OR = 3.2; p <.001), presence of rectal endometriosis with the largest diameter >25 mm (OR = 2.3; p = .004), and rectovaginal septum infiltration (OR = 2.3; p = .003). The optimal diagnostic balance was obtained considering at least 2 concomitant DE nodules and at least 1 indirect DE sign (area under the curve 0.75; 95% confidence interval, 0.72-0.79)., Conclusion: Specific indirect ultrasonographic findings should raise suspicion of PE in women undergoing preoperative assessment for DE. The suspicion of parametrial invasion may be critical to address patients to expert leading centers, where proper diagnosis and surgical treatment for PE can be performed., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: The recurrence of deep infiltrating endometriosis (DIE) after its surgical excision is a big problem: postoperative treatment is crucial., Objective: To compare two postoperative treatments: Dienogest and GnRH agonists., Design: Prospective Randomized Controlled Trial (RCT)., Patients: 146 women submitted to laparoscopic eradication of DIE with bowel and parametrial surgery., Interventions: Patients were randomized into two groups. Group A ( n  = 81) received Triptorelin or Leuprorelin 3.75 mg every 4 weeks for 6 months. Group B ( n  = 65) received Dienogest 2 mg/day for at least 6 months. A first interview made after six months valued compliance to therapy, treatment tolerability, pain improvement, and side effects. A second interview at 30 ± 6 months valued pain relapse, imaging relapse, and pregnancy rate., Main Outcomes: The primary outcome was to demonstrate the non-inferiority of Dienogest about the reduction in pain recurrence. Secondary outcomes were differences in terms of treatment tolerability, side effects, imaging relapse rate, and pregnancy rate., Results: Both Dienogest and GnRH agonists were associated with a highly significant reduction of pain at 6 and 30 months, without any significant difference ( p  < .001). About treatment tolerability, a more satisfactory profile was reported with Dienogest ( p  = .026). No difference in terms of clinical relapse, imaging relapse, and live births was found., Conclusions: Dienogest has proven to be as effective as GnRH agonists in preventing recurrence of DIE and associated pelvic pain after surgery. Also, it is better tolerated by patients.

Introduction: Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area., Area Covered: This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas., Expert Opinion: Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.

Introduction: Preoperative assessment of deep endometriotic (DE) nodules is necessary to inform patients about the possible treatments and provide informed consent in case of surgery. This study aims to investigate the diagnostic performance of rectal water-contrast transvaginal ultrasonography (RWC-TVS) and sonovaginography (SVG) in women with suspicion of posterior DE., Material and Methods: This prospective comparative study (NCT04296760) enrolled women with clinical suspicion of DE at our institution (Piazza della Vittoria 14 SRL, Genoa, Italy). Exclusion criteria were previous diagnosis of DE by imaging techniques or laparoscopy. All patients underwent RWC-TVS and SVG, independently performed by two gynecological sonologists blinded to the other technique's results. Patients underwent laparoscopic surgery within the following three months; imaging findings were compared with surgical and histological results., Results: In 208 of 281 (74.0%) patients included, posterior DE was surgically confirmed in rectosigmoid (n = 88), vagina (n = 21), rectovaginal septum (n = 34) and uterosacral ligaments (n = 156). RWC-TVS and SVG demonstrated similar sensitivity (SE; 93.8% vs 89.4%; p = 0.210) and specificity (SP; 86.3% vs 79.4%; p = 0.481) in diagnosing posterior DE. Specifically, both examinations had similar accuracy in detecting nodules of uterosacral ligaments (p = 0.779), vagina (p = 0.688) and rectovaginal septum (p = 0.824). RWC-TVS had higher SE (95.2% vs 82.0%; p = 0.003) and similar SP (99.5% vs 98.5%; p = 0.500) in diagnosing rectosigmoid endometriosis and estimated better infiltration of intestinal submucosa (p = 0.039), and distance between these nodules and anal verge (p < 0.001); only RWC-TVS allowed the estimation of bowel lumen stenosis. A similar proportion of discomfort was experienced during both examinations (p = 0.191), although a statistically higher mean visual analog score was reported during RWC-TVS (p < 0.001)., Conclusions: Although RWC-TVS and SVG have similar accuracy in the diagnosis of DE, RWC-TVS performed better in assessment of the characteristics of rectosigmoid endometriosis., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Research Question: Several studies have investigated reproductive outcomes following surgical treatment of colorectal endometriosis, mainly segmental colorectal resection. This study examines pregnancy and live birth rates of women with rectosigmoid endometriosis not treated by surgery., Design: A retrospective analysis of data collected between May 2009 and January 2020 related to 215 women affected by rectosigmoid endometriosis wishing to conceive. Patients had a diagnosis of rectosigmoid endometriosis by transvaginal ultrasonography and magnetic resonance imaging enema. Patients with estimated bowel stenosis >70% at computed tomographic colonography and/or subocclusive/occlusive symptoms were excluded., Results: During the median length of follow-up of 31 months (range 13-63 months), the total pregnancy and live birth rates of the study population were 47.9% and 45.1%, respectively. Sixty-two women had a live birth after natural conception (28.8%; 95% confidence interval [CI] 22.8-35.6%) with a median time required to conceive of 10 months (range 2-34 months). Eighty-three women underwent infertility treatments (38.6%, 95% CI 32.1-45.5%); among these, 68 patients underwent IVF either directly (n = 51) or after intrauterine insemination (IUI) failure (n = 17). Time to conception was significantly higher in women having conceived by IVF than in those having conceived naturally (P < 0.001) or by IUI (P = 0.006). In patients undergoing IVF cycles, a worsening of some pain and intestinal symptoms was observed., Conclusions: At median follow-up of 31 months, women with rectosigmoid endometriosis have a 48% pregnancy rate. However, these patients must be referred to centres specialized in managing endometriosis to properly assess symptoms and degree of bowel stenosis., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Over the last twenty years, segmental resection (SR) has been the technique most frequently used to treat bowel endometriosis. Nowadays, it is most commonly performed by laparoscopy; however, there is evidence that it can be safely performed by robotic-assisted laparoscopic surgery. Rectovaginal fistula and anastomotic leakage are the two major complications of SR; other complications include pelvic abscess, postoperative bleeding, ureteral damage, and anastomotic stricture. Several studies showed that SR causes improvement in pain and intestinal symptoms; nerve-sparing SR may improve the functional outcomes. The rates of postoperative recurrence of bowel endometriosis vary across the studies, possibly because of the different definitions of recurrence., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The impact of bowel endometriosis on fertility is unclear, and the optimal management of patients who wish to conceive is not well-defined. Infertile patients with bowel endometriosis may either undergo surgery to enhance fertility or assisted reproductive technology (ART). It is necessary to consider that some complications may occur in patients undergoing ART because of the ovarian stimulation needed during these procedures. Interpretation of the available data on fertility outcomes after colorectal surgery for deep endometriosis is difficult as several studies do not distinguish patients with real infertility from those wishing to conceive without proven infertility and outcomes of complex surgery are operator-dependent. The effect of bowel surgery to increase the likelihood of spontaneous conception is yet to be established. Limited data are available on fertility outcomes after the removal of endometriotic nodules without the excision of bowel endometriotic implants., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Transvaginal ultrasonography (TVS) should be the first-line investigation in patients with suspicion of deep endometriosis and, in particular, of rectosigmoid endometriosis. TVS cannot assess the presence of intestinal nodules located proximally to the sigmoid (such as ileal or cecal endometriotic nodules), because these lesions are beyond the field of the transvaginal probe. The ultrasonographic findings of rectosigmoid endometriosis are the presence of an irregular hypoechoic nodule in the anterior wall of the rectosigmoid colon. The learning curve for diagnosing rectosigmoid endometriosis by TVS is quite short; approximately, 40 scans are required to a sonographer who trained in general gynecologic ultrasonography to become proficient at diagnosing bowel endometriosis. Several meta-analyses confirmed the high diagnostic performance of TVS in diagnosing rectosigmoid endometriosis. The presence of "soft markers" (negative sliding sign and kissing ovaries) facilitates the diagnosis of rectosigmoid endometriosis. Enhanced TVS (rectal water-contrast transvaginal ultrasonography, sonovaginography, and tenderness-guided transvaginal ultrasonography) does not improve the performance of TVS in diagnosing rectosigmoid endometriosis. These investigations, however, may be useful to ascertain the depth of infiltration of endometriosis in the intestinal wall or the presence of rectal stenosis. Magnetic resonance imaging has the same performance of TVS in diagnosing rectosigmoid endometriosis; however, it should be recommended as a second-line technique in the preoperative workup of patients with previous equivocal TVS findings., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Pharmacotherapy has a key role in the management of endometriosis. However, a significant proportion of patients gains only intermittent or limited benefits. In this regard, alternative and novel drug delivery methods are of paramount importance to improve efficacy and compliance of available treatments and develop alternative medical approaches., Areas Covered: This review aims to provide the reader with a complete overview of available evidence about alternative and novel drug delivery methods for endometriosis pharmacotherapy and highlight new research lines., Expert Opinion: Progestins and estroprogestins, which represent the first-line therapy, are already available in different formulations, being employed for contraception. Nevertheless, evidence on their adoption is still limited for some drug delivery methods, such as vaginal rings, patches, and subcutaneous implants. Further research is needed to define better their clinical utility in patients with endometriosis. Nanotechnologies have been investigated as novel drug delivery methods able to target the drug at the disease level. However, data are very limited and preliminary, and further research is needed to consider a possible clinical application in endometriosis.

Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis. DCBE provides a complete overview of the entire colon and allows detecting cecal nodules. The accuracy of DCBE is operator dependent and, thus, it may have low specificity. It does not allow identifying the cause of the mass effect. DCBE requires the administration of barium and exposure to radiation. REU precisely estimates the distance between the rectosigmoid nodule and the anal verge. However, it allows investigating only the distal part of rectosigmoid, it misses anterior pelvic lesions, and it has poor sensitivity for the diagnosis of endometriomas. MDCT-e is accurate and reproducible in diagnosing intestinal endometriosis and in assessing its characteristics: the largest diameter of the nodule, the distance between the distal part of the nodule and the anal verge, and depth of infiltration of endometriosis in the intestinal wall. MDCT-e requires the administration of iodinated contrast medium (CM) and the exposure to radiations. CTC has good performance in the diagnosis of rectosigmoid endometriosis. It allows estimating the degree of intestinal stenosis CTC, and the distance between the intestinal endometriotic nodule and the anal verge. It requires exposure to radiations, and it may require the administration of an iodinated CM., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The use of three-dimensional (3D) transvaginal ultrasonography (TVS) has been investigated for the diagnosis of deep endometriosis (DE). This study aimed to evaluate if 3D reconstructions improve the performance of TVS) in assessing the presence and characteristics of bladder endometriosis (BE)., Design: This was a single-center comparative diagnostic accuracy study. Participants/Materials, Setting, Methods: Patients referred to our institution (Piazza della Vittoria 14 Srl, Genova, Italy) with clinical suspicion of DE were included. In case of surgery, women underwent systematic preoperative ultrasonographic imaging; an experienced sonographer performed a conventional TVS; another experienced sonographer, blinded to results of the previous exam, performed TVS, with the addition of 3D modality. The presence and characteristics of BE nodules were described in accord with International DE Analysis group consensus. Ultrasound data were compared with surgical and histological results., Results: Overall, BE was intraoperatively found in 34 out of 194 women who underwent surgery for DE (17.5%; 95% confidence interval: 12.8-23.5%). TVS without and with 3D reconstructions were able to detect endometriotic BE in 82.2% (n = 28/34) and 85.3% (n = 29/34) of the cases (p = 0.125). Both the exams similarly estimated the largest diameter of BE (p = 0.652) and the distance between the endometriotic nodule and the closest ureteral meatus (p = 0.341). However, TVS with 3D reconstructions was more precise in estimating the volume of BE (p = 0.031). In one case (2.9%), TVS without and with 3D reconstructions detected the infiltration of the intramural ureter, which was confirmed at surgery and required laparoscopic ureterovesical reimplantation., Limitations: The extensive experience of the gynecologists performing the ultrasonographic scans, the lack of prestudy power analysis, and the population selected, which may have been influenced by the position of the institution as a referral center specialized in the treatment of severe endometriosis, are limitations of the current study., Conclusion: Our results demonstrated the high accuracy of ultrasound for diagnosing BE. The addition of 3D reconstructions does not improve the performance of TVS in diagnosing the presence and characteristics of BE. However, the volume of BE may be more precisely assessed by 3D ultrasound., (© 2021 S. Karger AG, Basel.)

Introduction: Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary., Areas Covered: This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed from January 1990 to April 2020 in the electronic database MEDLINE, EMBASE, The Cochrane Library, and Web of Science., Expert Opinion: Based on the critical role of estrogens and the rate-limiting step in the production of the estrogens represented by the aromatase enzyme, AIs are a potential therapeutic option for women affected by endometriosis. Nevertheless, further research is needed to clarify the efficacy of AIs in this setting. Adverse effects need to be investigated to clarify the preventive role of add-back therapy. On that basis, AIs should be adopted only as second-line therapy in patients who are refractory to standard treatments in the setting of scientific research. Further studies should define best dosages, appropriate add-back therapies, administration routes, treatment length, and which patients may benefit more from AIs.

Research Question: The major causes of IVF failure in women with endometriosis have been attributed to decreased ovarian reserve, low embryo quality and impaired receptivity of the endometrium. Dienogest (DNG) has anti-inflammatory and anti-angiogenic activity and so may theoretically improve IVF outcomes in women with endometriosis. This study aimed to evaluate the administration of DNG before IVF in women with endometriosis who had previously failed one IVF cycle., Methods: This study was based on the retrospective analysis of a prospectively collected database, including 151 women who had failed a previous IVF cycle and all subsequent embryo transfers and had an imaging diagnosis of endometriosis. Patients either directly underwent IVF without receiving hormonal treatment or received 3 months of treatment with DNG (2 mg/daily) before IVF., Results: Eighty-eight (58.3%) patients underwent IVF without previous hormonal treatment, and 63 (41.7%) received pretreatment with DNG. The cumulative implantation, clinical pregnancy and live birth rates were significantly higher in the DNG-treated group (39.7%, 33.3% and 28.6%) than in the non-treated group (23.9%, 18.2% and 14.8%; P = 0.049, 0.037 and 0.043, respectively). The largest diameter of endometriomas significantly decreased after DNG pretreatment (P < 0.001). The use of DNG increased significantly the number of oocytes retrieved (P = 0.031), two-pronuclear embryos (P = 0.039) and blastocysts (P = 0.005) in women with endometriomas of diameter ≥4 cm., Conclusions: This study suggest that in patients with endometriosis, IVF outcomes can be improved by pretreatment with DNG. In particular, the use of DNG allows for better oocyte retrieval and blastocysts in patients with large endometriomas., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients' adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment., Areas Covered: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects., Expert Opinion: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

Objectives: Rectosigmoid involvement by endometriosis causes intestinal symptoms such as constipation, diarrhea, and dyschezia. A precise diagnosis about the presence, location, and extent of bowel implants is required to plan the most appropriate treatment. The aim of the study was to compare the accuracy of magnetic resonance with distension of the rectosigmoid (MR-e) with computed colonography (CTC) for diagnosing rectosigmoid endometriosis., Methods: This study was based on the retrospective analysis of a prospectively collected database of patients with suspicion of rectosigmoid endometriosis who underwent both MR-e and CTC, and subsequently were treated by laparoscopy. The findings of imaging techniques were compared with surgical and histological results., Results: Of 90 women included in the study, 44 (48.9%) had rectosigmoid nodules and underwent bowel surgery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the diagnosis of rectosigmoid endometriosis were 88.6%, 93.5%, 92.9%, 89.6%, and 91.1% for CTC, and 93.2%, 97.9%, 97.6%, 93.8%, and 95.6% for MR-e. There was no significant difference in the accuracy of both radiologic examinations for diagnosing rectosigmoid endometriosis (P = 0.344). However, MR-e was more accurate than CTC in estimating the largest diameter of the main rectosigmoid nodule (P < 0.001). The pain perceived by the patients was significantly lower during MR-e than during CTC (P < 0.001)., Conclusions: MR-e and CTC have similar diagnostic performance for the diagnosis of rectosigmoid involvement of endometriosis. However, MR-e is more accurate in the estimation of the largest diameter of main rectosigmoid nodule and more tolerated than CTC.

This study aimed to investigate the efficacy of the etonogestrel (ENG)-releasing implant in treating patients with rectovaginal endometriosis. The study was based on the retrospective analysis of a prospectively collected database, including symptomatic women who had ultrasonographic diagnosis of rectovaginal endometriosis. Patients were follow-up at 6, 12 and 24 months from the insertion of the ENG-releasing implant. The intensity of pain symptoms was evaluated using a visual analog scale. The volume of the nodules was estimated by virtual organ computer-aided analysis. The Endometriosis Health Profile (EHP-30) was used to evaluate quality of life. Overall, 43 women were included in the study. The 2-year continuation rate for the ENG-releasing implant was 93.0%. The treatment quickly improved the intensity of non-menstrual pelvic pain, deep dyspareunia, dysmenorrhea, and dyschezia. At 6-month follow-up, there were improvements in all domains of the EHP-30 compared with baseline. Further improvements in the EHP-30 results were observed only in pain sub score at 12-month follow-up and in emotional well-being sub score at 24-month follow-up. At 6-month follow-up the volume of the rectovaginal nodules was significantly lower compared with baseline; a further decrease was observed at 12- and 24-month follow-up. The treatment was well tolerated.

Endometriosis is a chronic disease characterized by the growth of endometrial-like glands and stroma outside the uterine cavity. Nowadays, the exact etiology of endometriosis is unclear and the interaction between a variety of environmental physical and chemical compounds may potentially promote the disease in women with an individual susceptibility. The first demonstration of a relation between an environmental factor and endometriosis was obtained with the chronic dietary exposure of a primate colony to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Besides the well-known dioxin's pathway of action, several papers are focusing on the role of epigenetic mechanisms, a way through which the genome responds to the environment and can lead to permanent changes in gene expression until affecting the phenotypes or cause disease. In this review, we focus on the possible role of dioxin epigenetics modification in endometriosis.

Endometriosis is a very complex condition and has a significant impact on the quality of life, psychological wellbeing and interpersonal relationships of affected women. Endometriosis symptoms progressively impair the woman's ability to carry out some daily activities and result in a perception of worsening health status and overall well-being. The impact of these symptoms has been only partially investigated, and further studies and clinical insights are needed to fully understand the extent of this condition. It has been shown that endometriosis is associated with considerable direct and indirect costs, comparable to those of major worldwide chronic diseases such as diabetes. In addition, endometriosis-related symptoms substantially interfere with the employment of affected women, resulting in many cases in several working days missed. In this scenario, the aim of this narrative review is to provide a general overview of the psychological and social impact of this disease, as well as the effects of different therapeutic options, on quality of life and general well-being.

Intestinal endometriosis occurs in 4% to 37% of women with deep endometriosis (DE). Noninvasive diagnosis of presence and characteristics of rectosigmoid endometriosis permits the best counseling of patients and ensures best therapeutic planning. Magnetic resonance enema (MR-e) is accurate in diagnosing DE. After colon cleansing, rectal distention and opacification improves the performance of MR-e in diagnosing rectosigmoid endometriosis. MR imaging cannot optimally assess the depth of penetration of endometriosis in the intestinal wall. There is a need for multicentric studies with a larger sample size to evaluate reproducibility of MR-e in diagnosis of rectosigmoid endometriosis for less experienced radiologists., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Endometriosis is a chronic gynecological disease that generally affects young and sexually active women in different stages of their development and sexual life. Because endometriosis affects about 5-10% of women in reproductive age, it is possible to estimate that about 2-4% of those who are sexually active may suffer from sexual dysfunction caused by this disease. Surgical and pharmacological treatments of endometriosis can improve the patient's sexual function in the medium and long term, but not necessarily lead to a definitive resolution of the sexual issue. For this reason, the ideal treatment should be conducted by a multidisciplinary team, with the aim to improve overall sexual functioning and not only to reduce the painful symptoms during intercourse. In light of these considerations, the aim of this narrative review was to provide a general overview about the impact of endometriosis on sexuality of women affected and the effectiveness of surgical and pharmacological treatments in improving sexual function.

Background and objective : Previous studies did not draw a definitive conclusion about the influence of the role of deep endometriosis (DE) and ovarian endometrioma (OE) as risk factor for developing adverse perinatal outcomes in patients affected by endometriosis. This study aimed to investigate if adverse fetal and maternal outcomes, and in particular the incidence of small for gestational age (SGA) infants, are different in pregnant women with OE versus pregnant women with DE without OE. Material and methods : This study was based on a retrospective analysis of a database collected prospectively. The population included in the study was divided into three groups: patients with OE, patients with DE without concomitant OE, and patients without endometriosis (controls). The controls were matched on the basis of age and parity. Demographic data at baseline and pregnancy outcomes were recorded. Results : There was no statistically significant difference in first trimester levels of PAPP-A, first and mid-pregnancy trimester mean Uterine Artery Doppler pulsatile index, estimated fetal weight centile, and SGA fetuses' prevalence for patients with OE, and those with DE without OE in comparison to health women; moreover, there was no statistically significant difference with regard to SGA birth prevalence, prevalence of preeclampsia, and five-minute Apgar score between these three groups. Conclusions : The specific presence of OE or DE in pregnant women does not seem to be associated with an increased risk of delivering an SGA infant. These data seem to suggest that patients with endometriosis should be treated in pregnancy as the general population, thus not needing a closer monitoring.

The non-surgical diagnosis of endometriosis is still challenging for the clinician. Ultrasonography and magnetic resonance imaging can be used to diagnose ovarian endometriotic cysts and deep infiltrating endometriosis; but their performance is poor in the diagnosis of initial stages of endometriosis. CA-125 and other serum markers (such as CA 19-9, serum protein PP14, interleukins, and angiogenetic factors) have been measured in women with endometriosis but they are not reliable for the diagnosis of the disease. Although several studies used proteomics technologies to identify plasmatic markers of endometriosis, the non-invasive diagnosis of endometriosis is far from being achieved. In this issue, Manousopoulou et al. compare the integrated quantitative proteomic profile of eutopic endometrium and serum of women with endometriosis and controls. 1214 proteins are differentially expressed in the eutopic endometrium and 404 proteins in the serum of the two study groups. 21 proteins are aberrantly expressed in both eutopic endometrium and serum of women with endometriosis. More work is needed to assess if the differentially expressed proteins identified in this study can be used as clinical markers of endometriosis., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: The primary objective of the study was to compare the performance of the rectal water transvaginal ultrasonography (RWC-TVS) with and without bowel preparation (BP) in diagnosing rectosigmoid endometriosis. The secondary objectives were to compare the performance of the 2 exams in estimating infiltration of the mucosa, length of the largest rectosigmoid nodules, distance of the nodules from the anal verge, and presence of multifocal disease., Methods: This prospective study included patients with pain symptoms and intestinal complaints suggestive of endometriosis. Patients underwent RWC-TVS with and without BP within an interval of 1 week to 2 months. Two independent and blinded gynecologists performed the exams. The results of the 2 exams were compared with surgical and histologic findings., Results: A total of 155 patients were included in the study; 92 patients had rectosigmoid endometriosis. There was no significant difference in the performance of RWC-TVS with or without BP in diagnosing rectosigmoid endometriosis (P = .727). There was no significant difference in the performance of RWC-TVS with or without BP in diagnosing infiltration of the mucosa (P = .424) and multifocal disease (P = .688), in estimating the main diameter of the largest nodule (P = .644) and the distance between the more distal rectosigmoid nodule and the anal verge (P = .090). The patients similarly tolerated the 2 exams (P = .799)., Conclusions: Bowel preparation does not improve the performance of RWC-TVS in diagnosing rectosigmoid endometriosis and in assessing the characteristics of these nodules., (© 2018 by the American Institute of Ultrasound in Medicine.)

Introduction: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis., Areas Covered: This review aims to give to the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research., Expert Opinion: Among the new drugs investigated, late clinical trials on gonadotropin-releasing hormone (GnRH) antagonists and aromatase inhibitors (AIs) have demonstrated the most promising results. For this reason, elagolix, a new GnRH-antagonist, recently received the approval by the Food and Drug Administration (FDA) for treating pain associated to endometriosis. Other drugs with innovative targets have been identified, but the majority of these compounds have only been evaluated in pre-clinical studies or early clinical trials. Thus, a further extensive clinical research is necessary to better elucidate their pharmacologic characteristics, their efficacy, and safety for the treatment of this benign chronic disease.

Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence., Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment., Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence., Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.

Background: The ureter is the second most common site affected by urinary tract endometriosis, after the bladder. Optimal strategies in the diagnosis and treatment of ureteral endometriosis (UE) are not yet well defined., Objective and Rationale: The aim of this study was to systematically review evidence regarding the epidemiology, pathophysiology, diagnosis, medical and surgical treatment, impact on fertility and risk of malignant transformation of UE., Search Methods: A systematic literature review, by searching the MEDLINE and PUBMED database until April 2018, was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/PROSPERO CRD42017060065). A total of 67 articles were selected to be included in this review., Outcomes: The involvement of the ureter by endometriosis is often asymptomatic or leads to non-specific symptoms. When the diagnosis is delayed, UE may lead to persistent hydronephrosis and eventually loss of renal function. Ultrasonography is the first-line technique for the assessment of UE; alternatively, magnetic resonance imaging provides an evaluation of ureteral type involvement. The surgical treatment of UE aims to relieve ureteral obstruction and avoid disease recurrence. It includes conservative ureterolysis or radical approaches, such as ureterectomy with end-to-end anastomosis or ureteroneocystostomy performed in relation to the type of ureteral involvement. Fertility and pregnancy outcomes are in line with those observed after surgical treatment of deep infiltrating endometriosis (DIE). Current evidence does not support the potential risk of malignant transformation of UE., Wider Implications: In this article, we review available evidence on ureteral endometriosis, providing a useful tool to guide physicians in the management of this disease. Diagnosis and management of UE remain a challenge. In relation to the degree of ureteral involvement and the association with other DIE implants, the surgical approach should be planned and carried out in an interdisciplinary collaboration between gynecologist and urologist.

Introduction: Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects., Areas Covered: The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials., Expert Opinion: Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.