Pelvic Pain Research Articles

Endometriotic Tissue-derived Exosomes Downregulate NKG2D-mediated Cytotoxicity and Promote Apoptosis: Mechanisms for Survival of Ectopic Endometrial Tissue in Endometriosis.

Endometriosis, affecting 10% of women, is defined as implantation, survival, and growth of endometrium-like/endometriotic tissue outside the uterine cavity, causing inflammation, infertility, pain, and susceptibility to ovarian cancer. Despite extensive studies, its etiology and pathogenesis are poorly understood and largely unknown. The prevailing view is that the immune system of endometriosis patients fails to clear ectopically disseminated endometrium from retrograde menstruation. Exosomes are small extracellular vesicles that exhibit immunomodulatory properties. We studied the role of endometriotic tissue-secreted exosomes in the pathophysiology of endometriosis. Two exosome-mediated mechanisms known to impair the immune response were investigated: 1) downregulation of NKG2D-mediated cytotoxicity and 2) FasL- and TRAIL-induced apoptosis of activated immune cells. We showed that secreted endometriotic exosomes isolated from supernatants of short-term explant cultures carry the NKG2D ligands MICA/B and ULBP1-3 and the proapoptotic molecules FasL and TRAIL on their surface, i.e., signature molecules of exosome-mediated immune suppression. Acting as decoys, these exosomes downregulate the NKG2D receptor, impair NKG2D-mediated cytotoxicity, and induce apoptosis of activated PBMCs and Jurkat cells through the FasL- and TRAIL pathway. The secreted endometriotic exosomes create an immunosuppressive gradient at the ectopic site, forming a "protective shield" around the endometriotic lesions. This gradient guards the endometriotic lesions against clearance by a cytotoxic attack and creates immunologic privilege by induction of apoptosis in activated immune cells. Taken together, our results provide a plausible, exosome-based mechanistic explanation for the immune dysfunction and the compromised immune surveillance in endometriosis and contribute novel insights into the pathogenesis of this enigmatic disease.

PELVIC CONGESTION SYNDROME: A REAPPRAISAL.

Pelvic congestion syndrome (PCS) is a poorly understood condition that can be associated with chronic pelvic pain and could impact quality of life. The diagnosis is often made by exclusion of other causes of pelvic pain. The purpose of our review was to provide an update on the etiology, anatomy, physiology, Identification, and the therapeutic management of pelvic congestion syndrome. We conducted a literature review involving publications from 2003 to 2024 in PubMed, Elsevier, Medline as well as manual searches of primary and review articles using keywords such as "pelvic veins", "embolization", "venography", "pelvic congestion syndrome", and "chronic pelvic pain". Pelvic Congestion Syndrome remains poorly understood. Symptoms can be non-specific and difficult to distinguish from other diseases; yet it is an important cause of chronic pelvic pain in women. To date, there have been only a small number of randomized trials and high-level evidence is still lacking. We call for an increased awareness of pelvic congestion syndrome and additional clinical studies in a large number of patients.

Sexual Function of Women with and without Pregnancy-Related Pelvic Girdle Pain and its Relationship with Physical Activity, Kinesiophobia and Body Image: A Cross-Sectional Comparative Study.

The aim of this study was to compare the sexual function of women with and without pregnancy-related PGP, and to investigate its relationship with physical activity (PA), kinesiophobia, and body image (BI). Demographic characteristics, sexual function (Pregnancy Sexual Response Inventory), PA (Pregnancy Physical Activity Questionnaire), kinesiophobia (Tampa Kinesiophobia Scale), and BI (Body Image in Pregnancy Scale) of 125 pregnant women were recorded. In the PGP group (n = 46), visual analogue scales were used to assess the pain intensity during resting and sexual activity, and Pelvic Girdle Questionnaire was used to evaluate the activity limitation. Although total sexual function and BI scores of the groups were similar (p > 0.05), dyspareunia during pregnancy and level of kinesiophobia were higher, and energy expenditure during moderate-intensity PA was lower in pregnant women with PGP (p < 0.05). The PGP group had moderate activity limitation and reported increased PGP intensity during sexual activities (p < 0.001). PA level was significantly correlated with sexual desire (r = 0.180), and overall sexual function was correlated with kinesiophobia (r = -0.344) and BI (r = -0.199) during pregnancy (p < 0.05). These findings suggest that pregnant women with PGP are more vulnerable to sexual dysfunctions, and there is a need to develop biopsychosocial framework-oriented management strategies which aim to improve PA level and to eliminate psychological factors such as kinesiophobia and negative BI.Clinical Trial Registration: NCT05990361.

Dual species transcriptomics reveals conserved metabolic and immunologic processes in interactions between human neutrophils and Neisseria gonorrhoeae.

Neisseria gonorrhoeae (the gonococcus, Gc) causes the sexually transmitted infection gonorrhea. Gc is a prominent threat to human health by causing severe lifelong sequelae, including infertility and chronic pelvic pain, which is amplified by the emergence of "superbug" strains resistant to all current antibiotics. Gc is highly adapted to colonize human mucosal surfaces, where it survives despite initiating a robust inflammatory response and influx of polymorphonuclear leukocytes (PMNs, neutrophils) that typically clear bacteria. Here, dual-species RNA-sequencing was used to define Gc and PMN transcriptional profiles alone and after infection. Core host and bacterial responses were assessed for two strains of Gc and three human donors' PMNs. Comparative analysis of Gc transcripts revealed overlap between Gc responses to PMNs, iron, and hydrogen peroxide; 98 transcripts were differentially expressed across both Gc strains in response to PMN co-culture, including iron-responsive and oxidative stress response genes. We experimentally determined that the iron-dependent TbpB is suppressed by PMN co-culture, and iron-limited Gc have a survival advantage when cultured with PMNs. Analysis of PMN transcripts modulated by Gc infection revealed differential expression of genes driving cell adhesion, migration, inflammatory responses, and inflammation resolution pathways. Production of pro-inflammatory cytokines, including IL1B and IL8, the adhesion factor ICAM1, and prostaglandin PGE2 were induced in PMNs in response to Gc. Together, this study represents a comprehensive and experimentally validated dual-species transcriptomic analysis of two isolates of Gc and primary human PMNs that gives insight into how this bacterium survives innate immune onslaught to cause disease.

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain

BackgroundChronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient’s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP.MethodsVaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2.ResultsSignificant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺.ConclusionsVaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

An unexpected case of an adnexal hydatid cyst in a pregnant woman: a case report

BackgroundCystic echinococcosis, also known as hydatid disease, is a chronic and endemic illness caused by infection with a parasite called Echinococcus granulosus. In Romania, this disease has an incidence rate of 5.6 per 100,000 individuals, which is the highest in the Dobrogea region. The liver is the most affected site, accounting for 68.8% of cases, followed by the lungs at 17.2%. While cases of hydatid disease in the genital organs are rare, occurring at an incidence rate of only 0.5%, it is worth noting that cases of this disease in pregnancy worldwide are also rare, occurring at an incidence rate of 1 in 20,000 to 1 in 30,000 pregnancies.Case reportA 15-year-old Eastern-European woman who was 12 weeks pregnant presented to the emergency room with acute pelvic pain, dysuria, and frequent urination. Her laboratory tests showed that she had a urinary tract infection, and pelvic ultrasound revealed that she had a mass on her right adnexa. Despite receiving treatment, her symptoms did not improve, and she had to undergo surgery to remove the mass, which turned out to be a hydatic cyst. She also had to undergo a cesarean section to deliver her baby owing to fetal distress during labor.ConclusionsThis medical case report provides a detailed description of a pelvic hydatid cyst that was discovered during pregnancy. What makes this case particularly noteworthy is the cyst’s unusual location—it was found at the level of the right broad ligament of the uterus. Despite the complexity of the situation, the patient was able to receive effective treatment and the cyst was successfully managed with great outcomes for both the patient and the newborn. We hope that this report serves as a valuable example of how medical professionals can navigate challenging cases and provide optimal care for their patients.

Ultrasound Appearance of Intravascular Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Case Report

A 43-year-old patient with a history of uterine fibromatosis was referred to our hospital for menometrorrhagia and pelvic pain. At the pelvic ultrasound, a highly-vascularized myometrial lesion in volumetric increase was described. An elongated, solid, hypoechoic, painless, and highly vascularized left parauterine mass was identified. On histological examination, a uterine smooth muscle tumor of uncertain malignant potential (STUMP) with intravascular invasion of the left uterine vein was diagnosed. The adnexa and peritoneum were free of disease. On a retrospective evaluation of the ultrasound images, we noticed that the intravascular lesion showed sonographic features comparable to the original mass. Moreover, the Color Doppler (CD) analysis revealed an interrupted blood flow within the left uterine vein. In this case, the ultrasound proved to be an accurate diagnostic tool. When inhomogeneous uterine masses are suspected, and a parauterine/paraadnexal mass surrounded by irregular vessels are identified, the sonographer should take into account a risk of intravascular invasion. The patency of uterine and ovarian vessels should be accurately evaluated, to guide a tailored patient surgical approach.

Comparison of dienogest or combinations with ethinylestradiol/estradiol valerate on the pain score of women with endometriosis: A prospective cohort study.

Endometriosis is one of the most frequent gynecologic disorders. The pathognomonic symptom of endometriosis is pelvic pain. The recommended pain medications are oral hormonal contraceptives, progestin therapy, danazol, gonadotropin-releasing hormone analogs, nonsteroidal anti-inflammatory drugs, and aromatase inhibitors. In this study, we aimed to compare the efficiency of costing dienogest (DNG) and low-cost oral contraceptives regarding visual analog scores (VAS) score of pelvic pain and also cancer antigen-125 (CA-125), anti-Mullerian hormone (AMH) levels, and size of endometrioma in the patients with endometriosis which is a chronic disease that requires a lifelong management plan. In our study, 18 to 45-year-old patients presented to our institution's gynecology and obstetrician department for various complaints over 2 years, and endometriosis diagnoses were included. Patients were divided into 3 groups (20 patients in each medication group) according to the given medication: cyclic DNG (Visanne) or 0.03 mg ethinylestradiol combined with 2 mg DNG (Dienille) or estradiol valerate combined with 2 mg DNG (Qlarista). We recorded all patients' CA-125/AMH values and VAS scores of pelvic pain. All patients gave informed consent. There was no statistically significant difference between pre-medication and post-medication levels of CA-125, AMH, VAS score, and cyst size in all groups. However, statistically, significant decreases were seen in the cyst size and VAS score, indicating response to therapy in all groups. In conclusion, we think it is more reasonable to use cost-effective oral contraceptive medications, which also cause common side effects, instead of costing DNG since all drugs have the same efficiency and success.

Robot assisted exploration of the Alcock canal: a novel surgical technique

ObjectiveTo demonstrate a safe and reproducible surgical approach to the Alcock canal with a full decompression of the pudendal nerve. SettingPudendal neuralgia, a condition causing debilitating pelvic pain, is traditionally managed through a trans-gluteal incision.1-2 This surgical approach offers limited visualization and ability for nerve decompression.3 With the current technique, a full exposure and decompression of the pudendal nerve was achieved. ParticipantsA 44-year-old para 2 with symptoms of left pudendal neuralgia. InterventionsA 44-year-old para 2 presented with burning vaginal pain radiating to the left groin that was aggravated with sitting. She underwent a robotic-assisted left sacrospinous ligament transection and fasciotomy of the obturator internus muscle for suspected pudendal neuralgia. The surgery was performed with three robotic ports using the daVinci® Xi robotic system. ConclusionWith the enhanced access to the pudendal nerve provided by the novel surgical technique demonstrated in this study, a more comprehensive nerve decompression can be performed. This technique was successfully applied to a patient with pudendal neuralgia. There were no immediate intra-operative or post-operative complications. In short-term follow-up, the patient had significant relief of preoperative symptoms. While all surgical procedures for pudendal neuralgia have a risk of pudendal nerve and vessel injury,4 the presented technique has the potential to limit these risks by providing an enhanced view of the relevant anatomy. Future adaptation and refinement of this technique may contribute to the advancement of the surgical management of pudendal neuralgia.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador

BackgroundChronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies.ObjectivesTo evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador.DesignA cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05.ResultsThe prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia.ConclusionThe prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

P-326 Improving quality of life and awareness of endometriosis patients using personalized web app with indications about non pharmacological support and lifestyle changes

Abstract Study question Is it possible to improve quality of life of endometriosis patients using a personalized web app suggesting non-pharmacological interventions and lifestyle changes ? Summary answer A personalized web app is useful to improve awareness and quality of life of endometriosis patients What is known already Our project is based on four main considerations: first, there is a lack of information and awareness about endometriosis symptoms and possible treatments among affected patients; second, there is no definitive cure yet and nor medications nor surgery can be considered as definitive solution; third, web instruments and social media are useful nowadays to spread knowledges about the disease; fourth, non-pharmacological support is a real instrument to better deal with the symptoms and improve quality of life. Our web app is located in this context. Study design, size, duration This is a pilot study structured on one year follow-up of symptoms and quality of life of patients with confirmed endometriosis, giving them non-pharmacological suggestions and lifestyle changes useful to better face the pathology using a personalized web app. So far, we collected data from 50 patients. Preliminary results will be based on six months followup. The project started in December 2023 Participants/materials, setting, methods Participants are patients with diagnosis of endometriosis -ultrasound,mri and surgery - between 24-45 years old, using a personalized web app in which suggestions about non-pharmacological support/lifestyle changes, given by a multidisciplinary team, are contained. Indications received are based on pelvic symptoms - dysmenorrhea, dyspareunia, chronic pelvic pain- and main systemic symptoms - chronic fatigue syndrome, migraine, bowel implications/endobelly, urinary disfunctions. Quality of life before and after the indications received was measured using EHP-30 questionnaire. Main results and the role of chance A multidisciplinary team - specialists in gynaecology, infertility, urology, pelvic floor, nutrition, chronic pain, acupuncture, psychology, yoga/pilates, law- created a web app in which indications about non-pharmacological treatments/lifestyle changes to face endometriosis symptoms are contained. We divided the indications based on main pelvic symptoms of endometriosis - dysmenorrhea, dyspareunia, chronic pelvic pain- and main systemic symptoms - chronic fatigue syndrome, migraine, bowel implications/endobelly, urinary disfunctions. For each protocol, in validation by Italian ministry of health and structured in six months indications to be followed, we gave correct informations about the pathophysiology of endometriosis, related symptoms and how to recognize them, which specialist patients should consult, what kind of supplements are useful to reduce chronic inflammation in addition/without medical therapy, implications on fertility, nutrition indications, psycological support, physical activity, when surgery should be considered or where to refer to have a proper treatment. We also created the first online community formed by specialists and patients: patients web groups are useful to share experiences, but there is risk of misinformation. The presence of specialists in a web-based community with patients could also make the difference. So far, following our indications, 50 patients reported a significant improvement in quality of life Limitations, reasons for caution Limitation in patients selection is the difference in methods of diagnosis, not always performed by specialists. We do not find reasons for caution: non-pharmacological support exists. Correct informations in unique source raise awareness, the role of supplements, pelvic floor treatments, acupuncture, nutrition, psycological support are widely recognized in literature Wider implications of the findings We aim to properly support patients in management of endometriosis. With easily wide-spreading instruments such a web app created by specialists, supported by social media and online community, we also aim to reduce the diagnostic delay. Results so far indicate improvement in quality of life among the participants. Trial registration number not applicable

P-336 Efficacy of Gonadotrophin (GnRH) antagonists for endometriosis-associated pelvic pain - A systematic review and meta-analysis

Abstract Study question Are Gonadotropin-releasing hormone (GnRH) antagonists effective and safe in managing pain associated with endometriosis? Summary answer GnRH antagonists seem effective and safe in managing endometriosis-associated pain for at least 12 weeks of use. There is uncertainty with the evidence. What is known already GnRH agonists are commonly used as effective second-line treatment for endometriosis-associated pain. However, these agonists have drawbacks and are not well-tolerated by many women. GnRH antagonists, offer potential advantages over the agonists while providing similar efficacy. They lack the initial stimulatory effects thereby avoiding the initial flare-up of symptoms, which is common with agonists. Furthermore, unlike agonists, which are mainly available as injections, the antagonist are also available as oral preparations, which allow titration of doses. In-vitro and animal studies have shown antagonists to induce regression of endometriotic lesions by apoptosis. However, their efficacy in relieving endometriosis-related pains remains uncertain. Study design, size, duration Extensive electronic search was conducted by the Cochrane Gynaecology and Fertility group, up to October 2023 to identify randomised controlled trials (RCTs) evaluating efficacy of GnRH antagonists in managing endometriosis-related pains compared with placebo and/or GnRH agonists. The main searched databases included CENTRAL, MEDLINE and EMBASE. Screening and selection of suitable studies were undertaken. Study eligibility criteria included treatment for ≥12 weeks, laparoscopically confirmed endometriosis and assessment of pelvic pain scores as the primary endpoint. Participants/materials, setting, methods Primary end-point was a change in endometriosis-related pain score after 12-week treatment with GnRH antagonists compared with placebo and/or GnRH agonists. Changes in pain and quality of life (QoL) scores and adverse-events of GnRH-antagonists were compared between the antagonist versus the agonist/placebo groups. Data were analysed using RevMan software (V5.4) to calculate the standard mean difference (SMD) for continuous data, and the risk ratios (RRs) with 95% confident intervals (95% CI) for categorical data. Main results and the role of chance Seven eligible RCTs (n = 3043) were included, all of which compared GnRH-antagonist versus placebo, and only three also compared versus GnRH-agonist (leuprorelin). The GnRH-antagonists included ASP1707, Elagolix, Linzagolix and Relugolix. Meta-analysis of overall pelvic pain data from seven RCTs (n = 1684) showed significantly greater reduction in pain scores after 12 weeks of GnRH-antagonist versus placebo at low (SMD -0.29 95%CI -0.39 to -0.19; I2=0) and high doses (SMD-0.53 95%CI -0.63 to -0.43, I2=38%). Similarly, meta-analysis of other pains (dysmenorrhoea, non-menstrual pain, and dyspareunia) showed significantly greater pain score reduction with GnRH-antagonists versus placebo. Meta-analysis of overall pelvic pain from two RCTs (n = 263) comparing GnRH-antagonist versus leuprorelin showed comparable reduction in pain scores after 12 weeks at low (SMD 0.33 95%CI 0.09 to 0.58, I2=44%) and high doses (SMD 0.06 95%CI -0.19 to 0.30, I2=0%). Similarly, meta-analysis of other forms of pain revealed comparable reductions of pain scores between both drugs. Meta-analysis of QoL data (2RCTs, n = 259) revealed significantly greater improvements in scores with leuprorelin versus antagonists at low (SMD 0.74 95% CI 0.46 to 1.01; I2=98%) and high doses (SMD 0.35, 95%CI, 0.09 to 0.60, I2=97%). The most frequently reported treatment-related side-effects were hot-flushes, headaches and nasopharyngitis. No life-threatening side-effects were reported. Limitations, reasons for caution There was high heterogeneity between studies (e.g. differences in antagonists and pain scoring systems). No information was provided on prior endometriosis surgery, which is a confounding factor. Additionally, declared COI by authors of all trials could introduce high risk of bias. Evidence certainty was therefore deemed low to very low. Wider implications of the findings GnRH-antagonists seem to offer a promising treatment for endometriosis-related pain, with comparable efficacy to the agonists, but with several potential advantages. However, given the low quality and uncertainty of the evidence in this meta-analysis, high quality RCTs with robust designs are needed before making any firm recommendations for clinical practice. Trial registration number not applicable

O-269 Long term efficacy of Linzagolix in women with endometriosis-associated pain

Abstract Study question Does once-daily linzagolix taken up to 12 months maintain pain reduction observed at 6 months in women with endometriosis? Summary answer Linzagolix alone or in combination with combined add-back therapy (ABT) for 12 months maintains improvements of endometriosis-associated pain (EAP) observed at 6 months. What is known already Linzagolix is an oral GnRH antagonist under development for EAP. In the EDELWEISS 3 study, the 200mg+ABT dose met its co-primary endpoints at 3 months by reducing dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) and secondary endpoints such as DYS, NMPP, overall pelvic pain and dyschezia as well as interference of pain with daily activities at 6 months. Linzagolix 75mg significantly reduced dysmenorrhea but not NMPP at 3 months. Both doses of linzagolix were well tolerated over 6 months of treatment. Study design, size, duration EDELWEISS 6 was the extension study of EDELWEISS 3, a placebo-controlled Phase 3 study, investigating linzagolix 75mg and 200mg+ABT for up to 6 months in women with moderate to severe EAP. Subjects who completed EDELWEISS3 were invited to enter the extension study for an additional 6-month treatment on the same linzagolix dose; placebo subjects were randomized to either active dose. After end of treatment, subjects entered a drug-free post-treatment period of 6 months. Participants/materials, setting, methods Women participating to EDELWEISS 6 received linzagolix for up to 12 months consecutively. Key efficacy assessments included dysmenorrhea and non-menstrual pelvic pain (NMPP), dyspareunia (assessed with a 4-point VRS), overall pelvic pain and dyschezia (assessed with an 11-point NRS), and interference of pain with daily activities (assessed with the EHP-30 pain domain) at Month 12. We report the results for dysmenorrhea and NMPP. Main results and the role of chance Of 484 participants in EDELWEISS 3, 353 (72.9%) entered EDELWEISS 6 and were evaluated for efficacy. Demographics were similar to EDELWEISS 3 with a mean age of 35 years, a BMI of 24kg/m2 and 99% of subjects being White. Mean (SD) monthly baseline dysmenorrhea and NMPP pain scores on the VRS were 2.28 (0.41) and 1.76 (0.45), respectively. The threshold for a meaningful pain reduction was established at Month 3, being -1.10 and -0.80 for dysmenorrhea and NMPP, respectively. At Month 3, the proportion of subjects with a reduction of dysmenorrhea of 1.10 or greater, and stable or decreased use of analgesics was 45.2% for the 75mg group and 75.4% for the 200mg+ABT group, which increased to 49.6% and 84.7%, respectively, at Month 6, the end of EDELWEISS 3. At Month 12, the end of EDELWEISS 6 treatment, the proportion of subjects was further increased to 55.9% and 91.0%, respectively. For NMPP, the proportion of subjects with a reduction of 0.80 or greater and stable or decreased use of analgesics at Month 3 was 36.5% for 75 mg and 51.7% for 200mg+ABT, increased to 54% and 61% at Month 6, and increased to 59.5% and 67.6%, respectively, until Month 12. Limitations, reasons for caution Edelweiss 6 is the extension of the previously reported double blind, placebo controlled Edelweiss 3 study. The results confirm efficacy of 200mg + ABT at 12 months. Longer term data is required to further understand efficacy of GnRH antagonists in women with endometriosis associated pain. Wider implications of the findings The linzagolix 200mg+ABT group provided substantial and sustained improvement in EAP symptoms. The 75mg which did not meet the primary endpoint in EDELWEISS 3 still demonstrated marked improvements. There exists a substantial need for different treatment regimens in women suffering from endometriosis. Trial registration number NCT04335591

O-021 Magnetic Resonance Imaging (MRI) evaluation of Quinagolide Vaginal Ring (QVR) treatment on endometrioma, Deep Infiltrating Endometriosis (DIE), and adenomyosis lesion characteristics: QLARITY trial results

Abstract Study question Can MRI provide a useful assessment of changes to endometrioma, DIE, and adenomyosis lesion burden resulting from QVR treatment? Summary answer MRI successfully measured changes in the number, size, diffusion, and perfusion biomarkers of endometriotic and adenomyotic lesions enabling evaluation of QVR treatment efficacy. What is known already Endometriosis and adenomyosis are associated with chronic pelvic pain, painful menses, and infertility. Determining treatment efficacy is reliant on patient reported outcomes (PRO) which are sensitive to response style effects and may lag changes in underlying pathology. Availability of biomarkers measuring lesion burden could accelerate the development of therapies treating disease rather than managing symptoms. MRI is routinely used in oncology to provide non-invasive biomarkers of treatment effect, a paradigm adapted in this trial. Quinagolide is a dopamine D2 receptor agonist formulated in an extended-release vaginal ring in development for treatment of endometriosis based on presumed inhibition of lesion angiogenesis. Study design, size, duration QLARITY was a randomized, placebo-controlled phase 2 trial investigating the mechanism of action of QVR (1080 µg) administered for four menstrual cycles. Randomization was 1:1 QVR (n = 35) to placebo vaginal ring (n = 32). Primary endpoint was change in the sum of lesion sizes by type from baseline to end of cycle 4 as measured by MRI. Secondary endpoints included changes in lesion volume, PROs and adverse events. MRI-derived imaging biomarkers were analyzed as exploratory endpoints. Participants/materials, setting, methods Women, 18-45 years old with at least one type of lesion (endometrioma, adenomyosis, and/or DIE) visualized by MRI, were enrolled. The analyses were performed by treatment for each of the three lesion types individually and for all types combined. Change in lesion size was analyzed using ANCOVA adjusted for baseline. Number of subjects with lesion regression was analyzed using a Chi-Square test. MRI-derived diffusion and perfusion imaging biomarkers were analyzed as exploratory endpoints. Main results and the role of chance Demographics and baseline characteristics were comparable between treatment groups. Patients had a mean age of 36.1 years and had been diagnosed for 5.25 years on average. Most patients (n = 42, 62.7%) had 2-4 lesions. No statistically significant changes in the sum of lesion sizes or PROs (Numerical Rating Scale, Biberoglu and Behrman Scale, and Endometriosis Health Profile-30) after treatment were noted, when compared to placebo. However, across all lesion types, a statistically significantly higher proportion of QVR patients than placebo patients demonstrated lesion regression of ≥ 65.0% volume (61.3% vs 35.5%, p = 0.042). In the DIE group, lesion regression occurred in more patients treated with QVR than those on placebo (36.8% vs 7.7%, p = 0.016). For diffusion imaging biomarkers, a significant difference in the diffusion coefficient standard deviation of DIE lesions (p = 0.039) was found in the QVR group compared to placebo. For perfusion imaging biomarkers, a statistically significant relationship with the treatment was identified in the endometrioma group for the 25th percentile of difference in fractional volume of extravascular extracellular space (mean difference −1.69, p = 0.009) from baseline. Incidence and severity of adverse events were similar between QVR and placebo. Limitations, reasons for caution MRI cannot currently detect superficial, highly vascularized endometriosis, which may be more responsive to QVR treatment than the more advanced stage of endometriosis (indicated by relatively large endometrioma and DIE) imaged in QLARITY. Moreover, 4 cycles may not be of sufficient duration for optimal treatment of these lesions. Wider implications of the findings QLARITY provides support for the use of MRI to diagnose and characterize changes in endometriotic/adenomyotic lesions. It is also the first MRI characterization of the placebo response in this population. Imaging biomarkers show promise in generating insights. QVR is safe and well tolerated; further studies of its efficacy are warranted. Trial registration number NCT03749109

MRI Imaging Appearance in Mullerian Duct Anomalies

Abstract Background Müllerian duct anomalies include a complex spectrum of anatomical anomalies that arise from deviations during the normal development of the Müllerian ducts. In paediatrics, such defects cannot present with any clinical symptoms before puberty, yet, they can also have obstructive symptoms or a mass effect due to presence of a non communicating rudimentary horn or transverse vaginal septum. At the beginning of puberty, girls with these anomalies might have primary amenorrhea, pelvic pain or endometriosis. Müllerian duct anomalies have also associated with a variety of other congenital abnormalities. Aim of the Work To review MRI features of Mullerian Duct Anomalies and classify them according to ASRM and ESHRE-ESGE classifications. Patients and Methods The study was a case series study that included 37 patients who underwent pelvic MRI at Radiology Department “Ain Shams University hospitals” in Cairo, Egypt. Results In our study, Hypoplastic, Agenesis and Didelphysis found to have the same ratio of (21.6%), while Bicornuate uterus was (13.5%), septate (8.1%), unicornuate and transverse vaginal septum all were of (5.4%) incidence and the least common was arcuate uterus with (2.7%) incidence. Conclusion MRI is a highly helpful technique for evaluating female genital abnormalities and is able to consistently provide the essential imaging characteristics for the accurate identification of Mullerian malformations. Additionally, incidental pelvic disease and any related renal abnormalities may be thoroughly evaluated by MRI in a single scan, removing the need for additional diagnostic procedures.

P-289 Optimising the detection of obliterated Pouch of Douglas for endometriosis diagnosis, by combining unpaired endometriosis ultrasounds and magnetic resonance imaging using Artificial Intelligence

Abstract Study question Can we improve the diagnostic accuracy of the detection of POD obliteration in endometriosis magnetic resonance imaging, by leveraging results from unpaired eTVUS data sets? Summary answer We illustrate effective multimodal analysis methods improve POD obliteration detection accuracy from eMRI datasets, with an Area Under the Curve (AUC) from 65.0% to 90.6%. What is known already Traditionally, women investigated for pelvic pain and endometriosis, wait 6.4 years for laparoscopic diagnosis. There is a need for a more timely, non-invasive, accessible diagnostic tool. IMAGENDO is designed to combine eTVUS and eMRI using Artificial Intelligence (AI) to address this delay. We have previously demonstrated detection of pelvic endometriosis, including Pouch of Douglas (POD) obliteration, has a 95% specificity from endometriosis ultrasounds (eTVUS) and 72% from endometriosis magnetic resonance imaging (eMRI). This preliminary data has shown our novel multimodal AI approach, using imaging data from eTVUS and eMRIs, can improve diagnostic accuracy when detecting POD obliteration in endometriosis. Study design, size, duration The IMAGENDO study is a program of research designed to create a new diagnostic algorithm for endometriosis. The first part of the study describes the development of our initial algorithm using retrospective cross sectional transvaginal ultrasounds (n = 749), and magnetic resonance images (n = 89 private, n = 8984 public) from 9822 participants overall aged 18 to 45 years, collected between September 2011 and September 2022. Participants/materials, setting, methods Using public MRIs, we pre-trained a machine learning model, and fine-tuned the algorithm using private eMRIs to detect POD obliteration. Then unpaired eTVUSs were introduced to further improve our diagnostic model. We used a machine learning method known as Masked Autoencoder pretraining, which is unsupervised learning reconstructing masked data to generate a larger dataset. Then we embedded the data, compressing a large dataset into a small representation with the most salient features. Main results and the role of chance Scant training samples limited the generalisability of a 3D Vision Transformer to classify POD obliteration from MRI volumes, with an Area Under the Curve (AUC) of 65.0%. However, the masked auto-encoder pre-training partially mitigates this issue, improving the AUC to 87.2%. Adding knowledge distillation, and training a 3D Vision Transformer from scratch on such a small dataset is still challenging, with an AUC of 66.7%. However, adding both together: The knowledge distillation performance of 3D Vision Transformer with masked auto-encoder pre-training reaches an AUC of 77.2%, worse than without knowledge distillation, with an AUC of 87.2%. This could be due to the excessive domain shift between the pre-training dataset and TVUS dataset. However, fine-tuning the model from masked auto-encoder pre-training, the model improves accuracy from AUC=87.2% to AUC=90.6%. With all the steps using unmatched imaging from an alternative modality, this model ultimately demonstrated improvement in the AUC from 65% to 90% on our private MRI dataset. This is the first POD obliteration detection method that distils knowledge from TVUS to MRI using unpaired data, aiming to improve diagnostic accuracy of endometriosis from MRI; and the first machine learning method automatically detecting POD obliteration from MRI data to diagnose endometriosis. Limitations, reasons for caution Our eMRI datasets had some confounding problems, present as a result of artefacts, mislabelling, and misreporting. These were resolved using model checking, student auditing and expert radiology review. We will further test our algorithm with a diagnostic test accuracy study on at least two test cohorts. Wider implications of the findings Pre-training using digital data from different imaging modalities can improve the diagnosis of endometriosis especially when either imaging modality is missing. Provided specialist scanning is available, women with endometriosis will be able to obtain faster diagnosis prior to surgery. Trial registration number ACTRN12623000646640

A systematic literature review on patient-reported outcome domains and measures in nonsurgical efficacy trials related to chronic pain associated with endometriosis: an urgent call to action.

Endometriosis, a common cause for chronic pelvic pain, significantly affects quality of life, fertility, and overall productivity of those affected. Therapeutic options remain limited, and collating evidence on treatment efficacy is complicated. One reason could be the heterogeneity of assessed outcomes in nonsurgical clinical trials, impeding meaningful result comparisons. This systematic literature review examines outcome domains and patient-reported outcome measures (PROMs) used in clinical trials. Through comprehensive search of Embase, MEDLINE, and CENTRAL up until July 2022, we screened 1286 records, of which 191 were included in our analyses. Methodological quality (GRADE criteria), information about publication, patient population, and intervention were assessed, and domains as well as PROMs were extracted and analyzed. In accordance with IMMPACT domain framework, the domain pain was assessed in almost all studies (98.4%), followed by adverse events (73.8%). By contrast, assessment of physical functioning (29.8%), improvement and satisfaction (14.1%), and emotional functioning (6.8%) occurred less frequently. Studies of a better methodological quality tended to use more different domains. Nevertheless, combinations of more than 2 domains were rare, failing to comprehensively capture the bio-psycho-social aspects of endometriosis-associated pain. The PROMs used showed an even broader heterogeneity across all studies. Our findings underscore the large heterogeneity of assessed domains and PROMs in clinical pain-related endometriosis trials. This highlights the urgent need for a standardized approach to both, assessed domains and high-quality PROMs ideally realized through development and implementation of a core outcome set, encompassing the most pivotal domains and PROMs for both, stakeholders and patients.

Prevalence of neuropathic pain in patients with symptomatic endometriosis: Assessment using the DN4 score

The mechanisms underlying pain in cases of endometriosis or chronic pelvic pain are complex, often involving various types of pain; mainly nociceptive pain, central sensitization, and neuropathic pain. Our main objective was to examine the prevalence of neuropathic pain in women with symptomatic endometriosis, and secondary, to explore the factors associated with this type of pain and to assess the prevalence of a positive PPSC score and a history of sexual violence within this population.This study is a retrospective, comparative, single-center cohort study conducted from September 2019 to January 2023. The presence of neuropathic pain was confirmed by a positive DN4 score, defined as greater than or equal to 4. The association with the following variables was studied: age, BMI, marital status, smoking, alcohol and drugs consumption, age at menarche, gestity, parity, duration of exposure to endometriosis, MRI locations, laparoscopy for endometriosis and post-laparoscopy r-ASRM classification, hormone treatment, associated symptoms, VAS, associated pathologies, infertility consultation, Pain Center consultation, EPH-5 score, positive PPSC score (≥5), and history of sexual violence.The prevalence of neuropathic pain was 44.1%. Younger age, being in a relationship, having a high EPH-5 score and undergoing laparoscopy for endometriosis are associated with neuropathic pain independently of other variables.Our study underscores the persistent high prevalence of neuropathic pain in endometriosis cases, emphasizing the importance of actively screening for it. Identifying neuropathic pain could prompt referrals to pain specialists, integrating it into a comprehensive multidisciplinary approach

Neurologic pelvic pain: Diagnosis and treatment, with attention to hip-spine-pelvis exam

This article summarizes the 2023 International Continence Society (ICS) Workshop 5 focused on neurologically mediated chronic pelvic pain (CPP) (Workshop 5). A team of experts share practical advice and tools for assessment, diagnosis and management relevant to pudendal neuropathy or other nerve entrapment, central nervous system diagnoses such as herniated disc, radiculopathy, Tarlov cyst, tethered cord, hip confounders, and systemic neuropathy such as small fiber neuropathy, neuroinflammatory disease (e.g. Lyme, Multiple Sclerosis) and central sensitization.

Vaginal complications of graft-versus-host disease after hematopoietic stem cell transplantation: a cross-sectional study

Background: Stem cell transplantation is a clinical approach used to treat certain types of cancers, such as hematologic malignancies. Graft-versus-host disease (GVHD) occurs in 30–70% of cases and often diminishes the quality of life of transplant patients. This study aimed to determine the prevalence of vaginal complications of GVHD following hematopoietic stem cell transplantation. Methods: This study employed an analytical cross-sectional design. All patients referred to Shariati Hospital in Tehran between 2019 and 2020 who underwent hematopoietic stem cell transplantation were considered for inclusion in this study if they met the inclusion criteria. Inclusion criteria encompassed nonnot sexually active women aged 18–70 who received stem cell transplantation more than 100 days prior. Exclusion criteria comprised patients who experienced GVHD during the first 100 days posttransplantation. Additionally, individuals over 75 and patients with metastatic cancer were excluded. Results: A total of 55 patients were recruited, with ages averaging 40±9.9 years for recipients and 38.5±12.8 years for donors. Notably, 63.3 and 58.2% of patients exhibited oral and ocular symptoms, respectively. Regarding genital involvement, 49.1% experienced vaginal symptoms, while 25.5% had vulvar involvement. Among the 27 patients with vaginal involvement, two (7.4%) were categorized as mild, 17 (63%) as moderate, and eight (29.6%) as severe. Univariate analysis identified reduced vaginal discharge [odds ratio (OR=6.56)], vaginal tightness (OR=6.23), pelvic pain (OR=5.50), and vaginal involvement (OR=3.81) as significant predictors of other organ symptoms. Moreover, vaginal involvement (OR=3.68) emerged as the sole significant predictor of the cooccurrence of oral, ocular, and other organ symptoms. In the multivariate analysis, reduced vaginal discharge (OR=8.24) and vaginal tightness (OR=3.92) significantly predicted other organ symptoms (P=0.009). Conclusion: Reduced vaginal discharge and vaginal tightness remained significant predictors of other organ symptoms.