Tailoring radicality in diaphragmatic surgery for deep endometriosis: A matter of choice.

Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.

Experimental and new investigational drugs for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids, the most prevalent benign tumors among reproductive-age women, pose treatment challenges that range from surgical interventions to medical therapies for symptom control. Progestins and estroprogestins effectively manage uterine bleeding by suppressing dysfunctional endometrium over fibroids. While GnRH agonists represent a crucial milestone in symptom treatment, their prolonged use results in menopausal-like symptoms and irreversible bone mineral density loss. Advancements in understanding fibroid pathophysiology have prompted the exploration of new compounds to overcome current therapy limitations. AREAS COVERED: This manuscript offers an updated overview of investigational drugs for symptomatic uterine fibroids. EXPERT OPINION: Despite ulipristal acetate's well-established efficacy as a selective progesterone receptor modulator (SPRM) in fibroid treatment, its prescription has declined due to the rare but severe risk of liver damage. Oral GnRH antagonists, like elagolix, relugolix, and linzagolix, with their novel pharmacodynamic properties, are gaining traction in fibroid management, inducing a dose-dependent reduction in circulating sex hormone levels. Ongoing research on natural compounds, such as vitamin D and epigallocatechin gallate (EGCG), presents emerging options for treating uterine fibroids. This evolving landscape reflects the ongoing efforts to improve therapeutic outcomes for individuals with symptomatic uterine fibroids.

Impact of surgery for endometriosis on the outcomes of in vitro fertilization.

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.

"From the tip to the deep of the iceberg": Parametrial involvement in endometriosis.

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.

Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s.

BACKGROUND: The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s. METHODS: The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers' databases, complemented by a cross-check of the reference lists. We used a combination of the search terms "polycystic ovary syndrome", "obesity" and "insulin resistance" with "metformin", "exenatide", "liraglutide", "semaglutide", "orlistat" and terms relevant to the topic of each paragraph (e.g., "pathophysiology", "metabolism", "infertility", "treatment"). RESULTS: All articles describing the mechanisms responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s, were considered for this review. CONCLUSIONS: The existing research on GLP-1 receptor agonists (GLP-1RAs) has not conclusively established a specific therapeutic use for these drugs. Additionally, the efficacy of the newer generation of GLP-1RAs, particularly in terms of dosage and duration of exposure, warrants more extensive research. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.

A postoperative tumor-specific death prediction model for patients with endometrial cancer: a retrospective study.

Background: Endometrial cancer (EC) is an epithelial malignancy occurring in the endometrium, with a 5-year mortality rate of above 10%. However, there is currently a lack of studies exploring the potential of a predictive model of tumor-specific death after surgery in these patients. Methods: From January 2015 to December 2017, data related to 482 patients with EC admitted to the Dushu Lake Hospital Affiliated to Soochow University were analyzed. Patients were divided into death (n=62) and survival (n=420) groups according to whether tumor-specific death occurred at 5 years postoperatively or not. The clinical characteristics of the two groups were compared, and the risk factors for tumor-specific death in patients with EC 5 years after surgery were investigated by logistics regression analysis. A nomogram prediction model was established according to the relevant risk factors. Results: Tumor size, Ki-67 positive rate, Federation International of Gynecology and Obstetrics (FIGO) stage, and the rate of vascular tumor thrombus between the two groups (P<0.05) were found to be the statistically significant factors. Positive Ki-67, tumor size >3.35 cm, stage III, and vascular tumor thrombus were factors that influenced the tumor-specific death at 5 years after surgery (P<0.05). The predictive model obtained an area under the receiver operating characteristic (ROC) curves in the training and verification sets of 0.847 [95% confidence interval (CI): 0.779-0.916] and 0.886 (95% CI: 0.803-0.969), respectively. Conclusions: The nomogram prediction model, which was established in this study, was proved to be valuable in predicting tumor-specific death 5 years after the surgery in patients with EC.

Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.

Ultrasonographic characterization of parametrial endometriosis: a prospective study.

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.

Cornual Pregnancy: Results of a Single-Center Retrospective Experience and Systematic Review on Reproductive Outcomes.

Background and Objectives: Cornual pregnancies (CPs) are rare forms of ectopic pregnancy. When abortion does not occur, it can be a life-threatening condition for the mother and can also impair future fertility. We present our experience in the diagnosis and management of CPs. A systematic review was also conducted to investigate the reproductive outcomes after treatment. Materials and Methods: Between January 2010 and December 2022, we performed a retrospective, cross-sectional, single-center, and descriptive data collection and analysis (ClinicalTrial ID: NCT06165770). The search for suitable articles published in English was carried out using the following databases (PROSPERO ID: CRD42023484909): MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Cochrane Methodology Register), Health Technology Assessment Database, Web of Science, and search register such as ClinicalTrial. Only studies describing the impact of CP treatment on fertility were selected. Results: Two studies were included in the systematic review. Seventeen patients suffering from CPs were selected. In our series, a pelvic ultrasound allowed for the diagnosis of a cornual localization in 35.30% of cases. Thirteen women (76.47%) underwent immediate surgical management. The laparoscopic approach was the most used (76.92%), with a laparotomic conversion rate of 30%. Four patients (23.52%) received medical treatment with methotrexate. After treatment, two patients managed to achieve pregnancy. Conclusions: CP is a rare form of ectopic pregnancy that can quickly become life-threatening for the mother. Ultrasound does not lead to a precise diagnosis in all cases. In the absence of complications and emergencies, laparoscopy is an approach that could be considered valid. For selected asymptomatic patients, medical treatment may be a valid alternative. The data from the studies included in the systematic review, although demonstrating a superiority of medical treatment in terms of future pregnancies, are heterogeneous and do not allow us to reach a definitive conclusion.

The Advantages of Next-Generation Sequencing Molecular Classification in Endometrial Cancer Diagnosis.

Endometrial cancer (EC) is the most frequent gynecological cancer. The ESGO/ESTRO/ESP 2020 guidelines identify prognostic groups based on morpho-molecular characteristics. This study aims to evaluate the clinical applicability of NGS analysis to define an appropriate risk class and to improve the diagnostic and prognostic stratification of ECs. Cases of serous carcinoma (OHEC) and high- (HGEC) and low-grade (LGEC) endometrioid carcinoma diagnosed with the morphological and immunohistochemical (IHC) protocols were considered. After a standardized pre-analytical phase, tumor DNA was semi-automatically extracted and analyzed using NGS with a panel of 14 genes. A total of 63 cases were considered. NGS analysis was successful in 60 cases; all of these were classified according to the new diagnostic algorithm. The molecular risk classification showed a good correlation with the morphological (k = 0.8). The study showed that the protocols of the pre-analytical and analytical phases used are robust and can lead to molecular results that fall within the standards required, which can be used in clinical practice for more precise diagnostic-therapeutic management of patients. The implementation of the classification is particularly relevant for better prognostic stratification of HGECs. In addition, the identification of a suspicious VUS in POLE questions the classification of truncating variants.

"Things Have Changed"-Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients.

OBJECTIVE: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. METHODS: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. RESULTS: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. CONCLUSIONS: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.

A review of phase II and III drugs for the treatment and management of endometriosis.

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.

Current Medical Therapy for Adenomyosis: From Bench to Bedside.

Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.

The nano-revolution in the diagnosis and treatment of endometriosis.

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.

Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. BACKGROUND: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. METHODS: Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, ß-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I-II; 14 resulted in FIGO III-IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). RESULTS: Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III-IV had a worse DFS (HR = 3.34; 95% CI: 1.1-10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27-21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6-32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7-34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2-11.9; p = 0.02). CONCLUSIONS: HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up.

Evaluation of Borderline Ovarian Tumor Recurrence Rate after Surgery with or without Fertility-Sparing Approach: Results of a Retrospective Analysis.

Borderline ovarian tumors (BOTs) comprise 15-20% of primary ovarian neoplasms and represent an independent disease entity among epithelial ovarian cancers. The present study (Clinical Trial ID: NCT05791838) aimed to report a retrospective analysis of the management and outcomes of 86 consecutive BOTs patients, 54 of which were at a reproductive age. All patients with BOTs undergoing surgical treatment from January 2010 to December 2017 were included. Data were retrospectively reviewed. High levels of Ca-125 were observed in 25.6% of the FIGO stage I patients and 58.3% of the advanced disease patients. Fertility-sparing surgery and comprehensive surgical staging were performed in 36.7% and 49.3% of the patients, respectively. Laparotomy was the most frequent surgical approach (65.1%). The most common diagnosis at frozen sections was serous BOT (50.6%). Serous BOTs have significantly smaller tumor diameters than mucinous BOTs (p < 0.0001). The mean postoperative follow-up was 29.8 months (range 6-87 months). Three patients experienced a recurrence, with an overall recurrence rate of 3.5% (10% considering only the patients who underwent fertility-sparing treatment). BOTs have low recurrence rates, with excellent prognosis. Surgery with proper staging is the main treatment. Conservative surgery is a valid option for women with reproductive potential.

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I2 = 99%), decreasing to 1% (95% CI 0.00-0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Rituximab for endometriosis: Unlikely translatability from oncology due to safety concerns?

This letter discusses the article "The Effects of Rituximab on Experimental Endometriosis Model in Rats" by Dogan et al., which evaluated the potential therapeutic efficacy of rituximab in an experimental animal model of endometriosis. While the study showed promising results in decreasing the volume of endometriotic implants and differences in B-cell count and fibrosis score, rituximab is typically used as a therapy for B lymphocyte malignancies and has potential short-term and long-term side effects. Additionally, animal models for endometriosis have limitations, and novel models are still being developed. Therefore, further preclinical research is necessary to evaluate the safety and efficacy of rituximab as a potential treatment for endometriosis in humans.

"A Space Odyssey" on Laparoscopic Segmental Rectosigmoid Resection for Deep Endometriosis: A Seventeen-year Retrospective Analysis of Outcomes and Postoperative Complications among 3050 Patients Treated in a Referral Center.

STUDY OBJECTIVE: To evaluate the feasibility of laparoscopic rectosigmoid resection for bowel endometriosis (RSE), reporting surgical and short-term postoperative outcomes in a consecutive large series of patients. DESIGN: A retrospective cohort study. SETTING: Third-level national referral center for deep endometriosis (DE). PATIENTS: 3050 patients with symptomatic RSE requiring surgical treatment. INTERVENTIONS: Nerve-sparing laparoscopic resection for RSE perfomed by a multidisciplinary team. After collecting intraoperative surgical characteristics, postoperative complications were collected by evaluating the risk factors associated with their onset. MEASUREMENTS AND MAIN RESULTS: Clavien-Dindo IIIb postoperative complications were noted in 13.1% of patients, with anastomotic leakage and rectovaginal fistula accounting for 3.0% and 1.9%, respectively. Postoperative bladder impairment was observed in 13.9% of patients during hospital discharge but spontaneously decreased to 4.5% at the first evaluation after 30 days, alongside a statistically significant change towards global symptom improvement. Multivariate analyses were done to identify the risk factors for segmental bowel resection in terms of occurrence of postoperative major complications. Ultralow (≤5 cm from the anal verge), low rectal anastomosis (<8 cm, >5 cm), parametrectomy, vaginal resection, and previous surgeries seemed more related to anastomotic leakage, rectovaginal fistula, and bladder retention. CONCLUSIONS: Laparoscopic rectosigmoid resection for RSE seems an effective and feasible procedure. The surgical complication rate is not negligible but could be reduced by implementing a multidisciplinary approach, an endless improvement in nerve-sparing techniques and surgical anatomy, as well as technological enhancements. Real future challenges will be to reduce the time for the first diagnosis of DE and the likelihood of surgical indications.