Endometriosis Phenotype Research Articles

Adenomyosis Localized in Both the Anterior and Posterior Myometrium Is Associated with Deep Rectal Endometriosis: A Retrospective Study

Background: Endometriosis and adenomyosis are two closely related, estrogen-dependent, benign gynecological diseases. The available evidence on their common pathogenesis and association is limited and often does not address the heterogeneity of both entities. The aim of our study is to investigate the association between different types and localizations of adenomyosis and endometriosis phenotypes, using magnetic resonance imaging (MRI) and laparoscopic findings. Methods: We performed a retrospective observational study involving premenopausal women over 18 years old who underwent laparoscopic surgery for endometriosis and were pre-operatively diagnosed with adenomyosis through MRI examination at the Cantonal Hospital of Schaffhausen, Switzerland between 2011 and 2022. Results: Of 130 patients with adenomyosis, 23 (17.7%) women had adenomyosis only in the anterior wall (group 1), 38 (29.2%) only in the posterior wall (group 2), and 69 (53.1%) in both the anterior and posterior wall (group 3). Women in group 1 experienced significantly more dysuria compared to the two other groups (p = 0.018), while the prevalence of other pain symptoms (dysmenorrhea, dyspareunia, dyschesia) was comparable between the groups. Women in group 3 had significantly thicker anterior and posterior myometrium compared to groups 1 and 2 (p < 0.001). Co-existence of deep rectal endometriosis was more frequent in women from group 3 compared to groups 1 and 2 (p = 0.039) and in women with adenomyosis in the outer (extrinsic) compared to adenomyosis in the inner myometrium (intrinsic) (p < 0.001). Conclusions: This study provides evidence of an association between the localization of adenomyosis and the distribution of concomitant endometriosis. Specifically, adenomyosis localized in both the anterior and posterior wall appears to be more proliferative compared to adenomyosis found only in the anterior or posterior wall. This is indicated by its association with higher uterine volume, thicker posterior junctional zone, and greater myometrial thickness and with a higher co-existence with deep rectal endometriosis. These findings support an association between the development of specific subtypes of both entities, which represents a valuable resource for the identification of future targets for the treatment and clinical management of adenomyosis and endometriosis.

Tertiary lymphoid structures in endometriosis

To determine whether tertiary lymphoid structures (TLSs), which reflect organized immune cell aggregates present in non-lymphoid tissues, are consistent features of endometriosis lesions. Detailed histopathological analysis of endometrial and lesion tissue from endometriosis patients and controls was performed. Multiplex immunofluorescence on select samples was then conducted to identify canonical cell populations present within TLSs: CD3+ and CD8+ T-cells, CD79a+ B-cells, CD208+ dendritic cells, CD21+ follicular dendritic cells (fDC), and PNAd+ high endothelial venules (HEVs). Histologically confirmed endometriosis patients (N=113; 44.3± 6.0) and control individuals (N=110; 44.6±7.1). Not applicable. Detection of TLSs as characterized by the presence of all canonical cell types that constitute TLS and structure morphology. Of the selected samples (N=18; 6 ectopic/eutopic/control), mature TLSs were identified in 3 ectopic tissue samples present on the ovary and fallopian tube, with immature TLSs (lacking fDC networks and HEVs) present throughout eutopic and control endometrial samples. These findings demonstrate the presence of TLSs across various endometriosis phenotypes, prompting further research into their significance within disease pathophysiology and the prognostic implications for patients.

Distribution of endometriosis phenotypes according to patients' age in adult women with surgical evaluation.

What is the distribution of endometriosis phenotypes according to age in adult women undergoing surgery? The phenotype of endometriosis did not significantly vary after 24 years old. The phenotypic evolution of endometriosis over time remains unclear. While adolescents can exhibit any type of endometriosis lesions, ovarian endometriosis (OMA) and/or deep-infiltrating endometriosis (DIE) tend to increase with age in young adults. In adulthood, understanding the evolution of lesions is crucial for disease management, but the literature on this subject is limited. This study aims to examine the distribution of endometriosis phenotypes in relation to age among adult patients requiring surgical treatment. This observational cohort study included patients aged between ≥18 and ≤42 years, who underwent surgery for benign gynecological conditions at our institution between January 2004 and December 2022. A standardized questionnaire was completed for each patient during a face-to-face interview conducted by the surgeon in the month preceding surgery. Women with histologically proven endometriosis were included. The distribution of endometriosis phenotypes (isolated superficial (SUP) endometriosis, OMA ± SUP, DIE ± SUP/OMA) was compared between young adults (≤24 years) and adults (>24 years) and among adults (25-28 years, 29-33 years, 34-38 years, 39 to ≤42 years) using univariate and multivariate analysis. The distribution of different subtypes of DIE (uterosacral ligament(s), vagina, bladder, intestine, and ureter), OMA size, and intensity of pain symptoms were also examined. A total of 1311 adult women with histologically proven endometriosis were included. In women aged 24 years or younger (n = 116), the distribution of endometriosis phenotypes differed significantly from women older than 24 years (n = 1195): The frequency of the DIE ± SUP/OMA phenotype was lower (41.4% versus 56.1%, respectively), while the rate of isolated superficial lesions was higher (from 32.0% versus 25.9%) (P = 0.001). In the group of women aged >24 years, a significantly higher proportion of vaginal DIE lesions (P = 0.012) and a lower proportion of uterosacral ligament DIE lesions (P = 0.004) were found compared to women aged ≤24years. No significant differences were observed in terms of endometrioma size. Between the ages of 25 and 42years, there were no significant changes in the distribution of endometriosis phenotypes after univariate and multivariate analysis. The distribution of subtype of DIE lesions did not significantly change with age between 25 and 42 years. Concerning pain symptom scores, there was a significant decrease with age for dysmenorrhea and dyspareunia. Inclusion of only surgical patients may have introduced a selection bias. Women referred to our center may have suffered from particularly severe clinical forms of endometriosis. This study highlights that endometriosis presentation did not change with age in adult women. Further research on endometriosis phenotype evolution is necessary to assist practitioners in clinical decisions and treatment strategies. None declared. N/A.

Norethindrone-Associated Transaminitis in Endometriosis Patients: A Case Series and Literature Review.

In this case series, we discuss 10 cases of norethindrone-induced transaminitis and conduct a literature review of this rare adverse event. A retrospective chart review was conducted on 10 patients (median age: 33 years) with diverse endometriosis phenotypes who received norethindroneand subsequently developed transaminitis, which is defined aselevated alanine transaminase (ALT) and aspartate transaminase (AST) levels. This condition was diagnosed in both asymptomatic and symptomatic patients, either during the work-up of acute symptoms or incidentally through routine lab tests. Our objective was to assess and characterize a case series of transaminitis associated with norethindrone use in endometriosis patients, detailing clinical presentations, management strategies, and outcomes. All cases exhibited normalization of liver function tests after discontinuation, occurring within one to 12 months with varying intervals of liver function testing. Patients receiving higher dosages (10 mg daily) demonstrated quicker resolution (average: four months). The reported adverse effects included nausea, vomiting, headache, rash, polyarthralgia, and abnormal uterine bleeding. Vigilant management, including prompt discontinuation, consistently resulted in the resolution of transaminitis. This study underscores the importance of continuous monitoring of liver function, even in asymptomatic patients on norethindrone therapy. Further investigations are imperative to identify specific groups susceptible to this adverse event.

P-285 Serum progesterone level may not impact ongoing pregnancy rate (OPR) in patients with endometriosis undergoing frozen-warmed-blastocyst transfer employing hormone replacement treatment (HRT) with subcutaneous progesterone

Abstract Study question Do serum progesterone (P4) levels on frozen embryo transfer (FET)-1 day impact OPRs in patients with endometriosis undergoing HRT-FET with subcutaneous progesterone (sc P)? Summary answer In HRT cycles employing sc P, serum P4 levels on FET-1 day do not affect OPRs in patients with or without endometriosis. What is known already In HRT-FET cycles employing vaginal P, reproductive outcomes are improved by serum P4 monitoring and employing a rescue protocol, if needed. However, there is paucity of data for the need of serum P4 monitoring in HRT cycles employing sc P. Endometriosis is associated with P4 resistance. There is only one study evaluating the impact of serum P4 levels on reproductive outcomes in patients with endometriosis; in this study lacking a control group and employing vaginal P gel 90 mg/12 hours supplemented by daily 50 mg intramuscular P, a threshold of 37.1 ng/ml has been reported for improved live birth rates. Study design, size, duration Retrospective cohort study. 451 consecutive patients undergoing their first HRT- vitrified warmed blastocyst transfer during November 2021-June 2023 at Anatolia IVF Centre were included. 44 patients had endometriosis with surgical and/or ultrasound findings and the remaining 407 patients did not harbor endometriosis. The presence of adenomyosis was an exclusion criterion. Following 10-12 days of 6 mg/day estradiol valereate use, sc P 25 mg/12hours (Prolutex, Ibsa) was administered. The primary outcome measure was OPR. Participants/materials, setting, methods Serum P4 levels were measured 4-5 hours after morning administration of sc P on FET-1 day. The impact of serum P4 on OPRs was assessed at various percentiles adjusting for female age, body mass index, prior birth, preimplantation genetic testing for aneuploidy, number/grade of blastocysts transferred. Multivariate regression models were performed in the whole cohort incorporating polynomial P4 terms and endometriosis interactions; optimal model for OPR prediction was selected using the lowest Akaike Information Criteria. Main results and the role of chance Patients with (27/44, 61.4%) and without (214/407, 52.6%) endometriosis had comparable OPRs. In the endometriosis group, the 10th, 50th, and 90th percentiles of serum P4 were 15.6, 25.1, and 35.4 ng/ml, respectively, compared to 14.9, 23.5, and 35.6 ng/ml in the non-endometriosis group. In the endometriosis group, the OPRs were 60.0%, 66.7%, 56.3%, and 60.0% for the <10p, 10-50p, 50-90p, >90p groups, respectively. These figures were 46.3%, 50.3%, 56.8%, and 51.2%, in the non-endometriosis group, respectively. In the endometriosis group, taking the 50-90p group as the reference, the adjusted odds ratios (aORs) for OPR of < 10p, 10-50p, and >90p groups were 1.24 [0.03, 50.45], 1.77 [0.31, 10.24], and 2.08 [0.05, 80.23], respectively. In the non-endometriosis group, the respective aORs were 0.85 [0.40, 1.79], 0.80 [0.49, 1.29], and 0.72 [0.34, 1.50]. In the multivariate regression analysis to determine the optimal model, neither serum P4 levels (aOR for linear term: 1.11 [0.98, 1.26]; for quadratic term: 0.998 [0.996, 1.00]) nor the diagnosis of endometriosis (OR: 1.48 [0.74, 2.98]) significantly predicted ongoing pregnancy after adjusting for confounders. Additionally, the optimal model did not include the interaction term, suggesting that endometriosis does not significantly modify the impact of serum P4 levels on OPRs. Limitations, reasons for caution The study’s limitations include retrospective study design, a limited sample size of the endometriosis cohort, absence of laparoscopy for endometriosis exclusion in the non-endometriosis group, and lack of data on endometriosis phenotypes. Wider implications of the findings In HRT-FET cycles employing sc P 25 mg/12hours neither serum P4 nor the presence of endometriosis have an impact on OPRs. Endometriosis may not modify the impact of serum P4 on OPRs suggesting a lack of P resistance in such cycles or the overcoming of P resistance by this regimen. Trial registration number not applicable

P-379 Fertility outcomes several years after fertility preservation for endometriosis

Abstract Study question To study the fertility outcomes of women who tried to conceive at least 2 years after fertility preservation (FP) for endometriosis. Summary answer To advise patients with endometriosis on the benefit of FP, particulary on the utilization rates of frozen oocytes and the actual chances of pregnancy What is known already Endometriosis is found in 25-40% of infertile patients. Due to the multiple and recurrent nature of lesions and the significant incidence of repeated ovarian surgery, endometriosis increase the risk of damaging the ovarian follicular stockpile. Since the revision of the French bioethics law (2014), women with endometriosis can be offered FP techniques. However, there is currently little data available in this population, limiting the possibility to establish formal recommendations Study design, size, duration A retrospective observational, bicentric cohort study conducted at Antoine Beclère and Jean Verdier University Hospitals.Inclusion criteria were: i) patients with confirmed endometriosis using imaging (pelvic MRI or ultrasound scan); ii) controlled ovarian hyperstimulation for FP between from July 1st 2013, and December 31st, 2019 (n = 200). The endpoint date was February 15, 2023, with data collected retrospectively. Participants/materials, setting, methods Cumulative incidences of pregnancy and live birth were calculated. Time to conception, time to utilization of oocytes, and predictive factors for pregnancy and live birth were assessed using logistic regression Cox models. Main results and the role of chance Among the 184 patients with available data after FP for endometriosis, 76 attempted to conceive (41%). The mean number of oocytes vitrified per patient were 14.7 ± 7.6 [8-20]. Patients attempting conception at least 2 years post-FP were more likely to have a partner at the first consultation (70.7% vs. 25.7%, p < 0.0001). Overall, 48 patients (43%) achieved a pregnancy, predominantly through spontaneous conception (50%), frozen-thawed oocytes (37.5%), or a new IVF attempt using fresh eggs (12.5%). Among those attempting conception, 31 (39%) reported a live birth. Cumulative chances of pregnancy at 4 years post-FP were estimated at 52% CI 95% [41% - 65%]. Utilization rates for frozen oocyteswere 7% CI 95% [4% - 12%] and 18% CI 95% [13% - 26%], respectively, 2 and 5 years post-freezing. Nulliparity was the only factor significantly associated with an increased probability of oocyte utilization (RR = 1.43 [1.0 - 2.06]). Limitations, reasons for caution The result should be interpreted with caution due to the small sample size of our study. Data were collected retrospectively and some information, concerning obstetrical and neonatal information where missing. Furthermore, the duration of the follow up time was too short to evaluate long-term fertility. Wider implications of the findings Despite endometriosis affecting fertility, our study revealed that half of pregnancies occurred spontaneously, irrespective of the endometriosis phenotype. These findings provide valuable insights into advising women on the utilization rates of frozen oocytes (7% to 18%) and the relatively high chances of natural conception after FP for endometriosis. Trial registration number NA

Surgical Treatment of Patients with Endometriosis in the Certified Endometriosis Centers of the DACH Region - A Subanalysis of the Quality Assurance Study QS ENDO pilot.

Introduction After puberty, at least 10% of all women and girls suffer from endometriosis. Surgery is useful for both the diagnosis and therapy. To date, quality indicators for the surgical treatment of endometriosis are lacking. QS ENDO aims to record the quality of care provided in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis. In the first phase of the study, QS ENDO real, the reality of care was recorded using a questionnaire. The second phase, QS ENDO pilot, investigated the treatment of patients who underwent surgery in certified endometriosis centers in a defined time-period. Material and Methods The surgical data of 10 patients from each of the 44 endometriosis centers in the DACH region was recorded using an online tool. Collected data included the approach used, the endometriosis phenotype, a description of the surgical site, resection status, histological confirmation, the use of a classification, and any complications. All operations were carried out in October 2016 as the defined time-period. The surgical approaches used were compared with the recommendations in the current guidelines. Results The data of 435 patients with a median age of 34years were evaluated. 315 (72.4%) were nulliparous. 120patients had given birth to at least one child and 42.5% (51) of them had delivered their child by caesarean section. About 50% of all patients also had deep infiltrating endometriosis in addition to ovarian endometriosis, and the median NAS score was 7.5. With regards to the surgical treatment, endometriomas were completely resected in 81% (94) of patients. 87.3% of patients underwent resection of peritoneal endometriosis. Forty-one patients had a hysterectomy, with a total hysterectomy carried out in 26 (63.4%) and a supracervical hysterectomy in 15 (36.6%) patients. Of the 59 patients with bowel endometriosis, half had segmental resection and half had shaving of the anterior rectal wall. Complications requiring revision occurred in 0.9% of cases. Conclusion The surgical procedures carried out in the certified endometriosis centers of the DACH region are largely in line with the recommendations for appropriate surgical approaches in the current standard guidelines.

The interplay between systemic inflammatory factors and endometriosis: A bidirectional mendelian randomization study

ObjectiveTo utilize vast genetic data to reveal the interplay between 41 systemic inflammatory factors and endometriosis. DesignBidirectional Mendelian randomization study. Mains outcome measuresThis study obtained believable genetic instrumental variables for systemic inflammatory factors. The effect of systemic inflammatory factors on different endometriosis phenotypes, and the effect of endometriosis on the concentrations of systemic inflammatory factors were investigated. ResultsIn this mendelian randomization study, we found 20 causal relationships involving 18 systemic inflammatory factors and it was shown that Monocyte chemotactic protein-1, Macrophage inflammatory protein-1a, Granulocyte colony-stimulating factor, Macrophage migration inhibitory factor, Interleukin-4, Interleukin-5, Interleukin-8, Interleukin-9, Interleukin-12p70, Interleukin-16, and Interleukin-17 may be the upstream causes of endometriosis (P<0.05). Additionally, if the definition of exposure in the mendelian randomization was endometriosis, it could suggestively cause an increase in Eotaxin, cutaneous T-cell attracting chemokine, and Interferon gamma-induced protein 10 levels, and a decrease in growth-regulated oncogene-alpha, Interleukin-2 receptor, alpha subunit, platelet-derived growth factor BB, and Interleukin-18 (P<0.05). Reverse causality was not observed between a single systemic inflammatory factor and endometriosis. ConclusionsOur findings indicate that several systemic inflammatory factors may act as the initiator at the onset of endometriosis. Additionally, several other inflammatory factors are far more probable to involved downstream during disease development.

Endometriosis: A Narrative Review

Although much progress has been made since endometriosis was first scientifically described centuries ago, numerous unanswered questions still surround this chronic, inflammatory condition. For instance, one theory on the pathogenesis of endometriosis suggests that the condition begins from retrograde menstrual flow implanting on surfaces in the abdomen and pelvis (Samson’s theory), which is a logical mechanism given the high rates of endometriosis in patients with obstructive anomalies of the lower genital tract and significant retrograde flow. This explanation has many shortcomings however, as retrograde menstruation occurs more commonly than the reported 10% prevalence of endometriosis. Additionally, endometriosis lesions can be found in areas quite remote from the pelvis, such as the thoracic cavity. As such, research has been increasingly focused on identifying immune, genetic, and local environmental factors that likely play critical roles in the development of endometriosis. This growth of benign endometrial-like tissue outside of the uterus can sometimes be asymptomatic, but it can also cause debilitating pain, infertility, ovarian cysts (endometriomas), and can invade surrounding organs such as the bowel or bladder. There are three main phenotypes of endometriosis: superficial lesions, deeply infiltrating endometriosis (including nodules), and ovarian endometriomas. While the exact etiology may be obscure, the societal and economic impacts of this condition are undeniable. Patients diagnosed with endometriosis are at a significantly higher risk of absenteeism from work or school, lower quality of life, chronic pelvic pain, and are more likely to receive a mental health diagnosis such as depression or anxiety. Apart from direct and indirect incurred costs to patients (estimated at approximately $5000 per patient annually), at a national level the economic burden of endometriosis exceeds $2 billion annually in Canada, and approaches $80 billion in the USA.

Saliva-based microRNA diagnostic signature for the superficial peritoneal endometriosis phenotype

ObjectivePatients with superficial peritoneal endometriosis (SPE) present with symptoms suggestive of endometriosis but clinical and imaging exams are inconclusive. Consequently, laparoscopy is usually necessary to confirm diagnosis. The present study aimed to evaluate the accuracy of microRNAs (miRNAs) to diagnose patients with SPE from the ENDOmiARN cohort Study DesignThis prospective study (NCT04728152) included 200 saliva samples obtained between January and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy and/or MRI to confirm the presence of endometriosis. Among the patients with endometriosis, two groups were defined: an SPE phenotype group of patients with peritoneal lesions only, and a non-SPE control group of patients with other endometriosis phenotypes (endometrioma and/or deep endometriosis). Data analysis consisted of two parts: (i) identification of a set of miRNA biomarkers using next-generation sequencing (NGS), and (ii) development of a saliva-based miRNA signature for the SPE phenotype in patients with endometriosis based on a Random Forest (RF) model. ResultsAmong the 153 patients with confirmed endometriosis, 10.5 % (n = 16) had an SPE phenotype. Of the 2633 known miRNAs, the feature selection method generated a signature of 89 miRNAs of the SPE phenotype. After validation, the best model, representing the most accurate signature had a 100 % sensitivity, specificity, and AUC. ConclusionThis signature could constitute a new diagnostic strategy to detect the SPE phenotype based on a simple biological test and render diagnostic laparoscopy obsolete. PrécisWe generated a saliva-based signature to identify patients with superficial peritoneal endometriosis which is the most challenging form of endometriosis to diagnose and which is often either misdiagnosed or requires invasive laparoscopy.

Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability

Background Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients’ quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. Objective To evaluate DNG as a long-term treatment of endometriosis, focusing on patients’ compliance and side effects, also correlating with different phenotypes of endometriosis. Methods This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. Results At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. Conclusions DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

Data Mining Techniques for Endometriosis Detection in a Data-Scarce Medical Dataset

Endometriosis (EM) is a chronic inflammatory estrogen-dependent disorder that affects 10% of women worldwide. It affects the female reproductive tract and its resident microbiota, as well as distal body sites that can serve as surrogate markers of EM. Currently, no single definitive biomarker can diagnose EM. For this pilot study, we analyzed a cohort of 21 patients with endometriosis and infertility-associated conditions. A microbiome dataset was created using five sample types taken from the reproductive and gastrointestinal tracts of each patient. We evaluated several machine learning algorithms for EM detection using these features. The characteristics of the dataset were derived from endometrial biopsy, endometrial fluid, vaginal, oral, and fecal samples. Despite limited data, the algorithms demonstrated high performance with respect to the F1 score. In addition, they suggested that disease diagnosis could potentially be improved by using less medically invasive procedures. Overall, the results indicate that machine learning algorithms can be useful tools for diagnosing endometriosis in low-resource settings where data availability and availability are limited. We recommend that future studies explore the complexities of the EM disorder using artificial intelligence and prediction modeling to further define the characteristics of the endometriosis phenotype.

Causal effects of endometriosis stages and locations on menstruation, ovulation, reproductive function, and delivery modes: a two-sample Mendelian randomization study.

Endometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear. We explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women's menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed. MR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960-0.986) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965-0.988) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942-0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216-0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence. Our findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.

Are Adenomyosis and Endometriosis Phenotypes of the Same Disease Process?

In recent literature reviews, we concluded that the possibility that endometrial molecular aberrations are the sole or a necessary determinant of endometriosis and the Tissue Injury and Repair (TIAR) theory are yet to be convincingly proven. Here, we critically examine the theory that adenomyosis and endometriosis represent different phenotypes of a single disease. A common etiopathology for adenomyosis and endometriosis has been suggested because both conditions entail the presence of endometrial tissue at locations other than the lining of the uterus. There are wide differences in reported disease incidence and prevalence and, consequently, in estimates of the coexistence of both conditions. There are some similarities but also differences in their clinical features and predisposing factors. Each condition has a range of subtypes. These differences alone pose the question of whether subtypes of endometriosis and adenomyosis have different etiopathologies, and, in turn, this raises the question of whether they all share a common etiology. It is debatable whether the recognized differences between the eutopic endometrium in adenomyosis and endometriosis compared to those in unaffected women are the cause or the effect of the disease. The finding of common mutations, particularly of KRAS, lend support to the notion of shared predisposing factors, but this alone is insufficient evidence of causation.

Visualized peritoneal fluid variation in adolescents and young adults with endometriosis: is there more to it?

Peritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics, endometriosis type and lesion location in adolescents and young adults with endometriosis. We conducted a cross-sectional analysis among 545 patients undergoing surgery for endometriosis who enrolled in the Women's Health Study: from Adolescence to Adulthood cohort study. Patient characteristics, surgically visualized endometriosis phenotypes, and gross characteristics of peritoneal fluid were collected in compliance with World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. Chi-square or Fisher's exact tests were applied to test for differences across categories. Most of the patients were adolescents or young adults (86% age <25 years) of white race (89%), with only superficial peritoneal lesions and rASRM stage = I/II observed at surgery (both 95%). We observed variation in peritoneal fluid color across different menstrual cycle phases at time of surgery (p = 0.006). Among those who were cycling at time of surgery, endometriosis patients with red peritoneal fluid were most likely to be in the proliferative phase (49%) compared to the secretory phase (27%), while those with yellow or orange peritoneal fluid were most likely to be in the secretory phase (57% and 86% respectively). Yellow color was significantly less common in those taking combined oral contraceptives but much more common with progesterone only formulation exposure (p = 0.002). Peritoneal fluid volume did not differ by cycle phase but was more likely to be low (≤6 ml) for those exposed to hormones at time of surgery (p = 0.01). Those with acyclic pelvic pain were less likely to have red peritoneal fluid (p = 0.001) but had greater volume (p = 0.02) compared to those without. Our findings highlight the importance of accounting for menstrual cycle phase and hormonal exposures when designing research using peritoneal fluid samples and inferring from biomarker results intended to advance our understanding of endometriosis and associated symptom pathophysiology.

Co-Existence of Endometriosis with Ovarian Dermoid Cysts: A Retrospective Cohort Study.

Both endometriosis and ovarian dermoid cysts are benign conditions characterized by the presence of well-differentiated tissues in ectopic locations. The presence and surgical excision of these entities can potentially impact ovarian reserves, contributing to reduced chances of future pregnancy. The objective of our study is to investigate the bidirectional association between endometriosis and ovarian dermoid cysts, as well as to analyze the clinical characteristics of patients diagnosed with both conditions. A retrospective cohort study was conducted, including women who underwent laparoscopy and received histological diagnoses of endometriosis and/or dermoid cysts between 2011 and 2019 at the Cantonal Hospital of Schaffhausen. We identified 985 women with endometriosis and 83 women with ovarian dermoid cysts. Among these groups, 22 women presented with both endometriosis and ovarian dermoid cysts. The majority of the above patients had endometriosis stage rASRM I-II (72.7%), with peritoneal endometriosis being the most common phenotype of endometriosis (77.2%). Out of the 14 patients with a desire for future pregnancy, the majority (11/14, 78.5%) had an EFI score of 7-8. The prevalence of bilateral ovarian dermoid cysts was higher in women with both ovarian dermoid cysts and endometriosis in comparison to women with ovarian dermoid cysts without endometriosis (18% vs. 6.5%). Our study revealed that 26.5% of women with ovarian dermoid cysts also had endometriosis, a notably higher prevalence than observed in the general population. Clinicians should be aware of this co-existence, and preoperative counseling should be an integral part of the care plan for affected individuals, where the potential risks and the available options for fertility preservation should be discussed in detail.

Causal relationship between endometriosis with infertility and ankylosing spondylitis

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

Psycho-emotional status in patients with endometriosis-associated pain syndrome in various disease phenotypes

BACKGROUND: Patients with endometriosis-associated pain syndrome in combination with anxiety or depression have lower treatment effectiveness and satisfaction with both the disease itself and the pain syndrome compared to patients with pain syndrome but without depression or anxiety.&#x0D; AIM: The aim of the study is to assess the relationship between psychosocial status and endometriosis-associated pain syndrome in patients with different phenotypes of endometriosis using pain assessment scales, psychosocial state assessment scales, and quality of life assessment scales.&#x0D; MATERIALS AND METHODS: We examined 81 patients using a number of questionnaires: Visual Analogue Scale, Numeric Rating Scale, Hospital Anxiety and Depression Scale, Beck Depression Scale, Spielberger State-Trait Anxiety Inventory, and Short Form-36 quality of life assessment. The patients were divided into three groups: isolated adenomyosis (n = 39), adenomyosis combined with external genital endometriosis (n = 21), and the control group (n = 21).&#x0D; RESULTS: Our study has shown that patients with adenomyosis combined with external genital endometriosis had the highest scores on all questionnaires for assessing anxiety and depression, as well as a low quality of life in general, which significantly differed from those in the control group (p 0.05). The results in the group of women with isolated adenomyosis are not so unambiguous and, overall, somewhat better than in the group of patients with adenomyosis combined with external genital endometriosis, but significantly worse compared to the control group. When assessing the severity of dysmenorrhea, higher scores were also found in the group of women with adenomyosis combined with external genital endometriosis: 6.64 2.11 cm (Visual Analogue Scale) and 6.9 2.05 cm (Numeric Rating Scale), while in the group of women with isolated adenomyosis, the scores were 5.29 1.9 cm and 5.83 1.72 cm, respectively (p = 0.028). Women in the control group had no pain syndrome.&#x0D; CONCLUSIONS: Poor mental and physical health scores obtained in this study in women with external genital endometriosis dictate the need for an objective and multicomponent assessment of the psycho-emotional status in patients, followed by complex treatment and team management with related specialists.

P-375 Effect of D-Chiro-Inositol in a mouse model of endometriosis

Abstract Study question Can D-Chiro Inositol administration mitigate the phenotype of endometriosis in a mouse model? Summary answer Based on an endometriosis mouse model, we demonstrated that administration of D-Chiro Inositol can reduce development of endometriotic lesions. What is known already Endometriosis, a disease affecting 5-10% of women of reproductive age, is characterized by the spread of endometrial-like tissue outside the uterine cavity that produces ectopic endometriotic lesions causing pain and infertility. The sensitivity of endometriosis to estrogens is a characteristic that can be used for therapeutic purposes. D-Chiro Inositol (DCI), one of the nine isomers of Inositol, is known to decrease the CYP19A1 aromatase gene expression in granulosa cells. Based on these premises, it was suggested that treatment with DCI may have clinical application in conditions where decreased estrogen levels is required. Study design, size, duration To address the study question, a mouse model of endometriosis was generated. Out of 20 CD1 mice, 4 mice were randomly selected as donors of uterine fragments and the remaining 16 were recipient mice. The first day after transplantation, mice were randomly assigned to four experimental group which received for 28 days 2ml of water containing: none (CTRL); DCI 0.4mg (DCI 0.4); DCI 0.2mg and Dienogest 0.33ng (DCI 0.2+DG 0.33); DG 0.67ng (DG 0.67). Participants/materials, setting, methods Uterine horns were removed from donor mice at the diestrous stage of the reproductive cycle. The tissue cut into fragments was inoculated in recipient mice by intraperitoneal injection. Four weeks after induction, all mice were sacrificed. Their endometriotic lesions were excised, measured by number and size, and examined for the presence of blood vessels vascularization under stereomicroscope. Then, lesions were processed for histology examination by hematoxilin-eosin (H&amp;E) and Azan Mallory staining. Main results and the role of chance Endometriotic lesions developed in recipient mice met all criteria for endometriosis, including the presence of endometrial epithelial and stromal cells, and encapsulation in neighboring tissues or organs. The lesions number was reduced in all the treatment groups when compared to control (p &amp;lt; 0.05, t-test), and no differences were observed among DCI 0.4, DCI 0.2+DG 0.33 and DG 0.67. Concomitantly the rate of vascularized lesions was lower in the treated groups, with more pronounced effect in the DCI 0.4 group where no vascularized lesions were observed (p &amp;lt; 0.05, t-test). The histological analysis revealed a marked reduction of endometriotic foci in all groups. These results provide evidence that DCI can reduce development and vascularization of endometriotic lesions in a mouse model, an effect that is not observed when it is employed at lower dose in association with DG. Although molecular mechanisms underlying DCI effects requires further investigation, present findings support the hypothesis that DCI could be more effective than DG in mitigating endometriosis phenotype. Limitations, reasons for caution Results from animal studies should be extrapolated to humans with caution. Wider implications of the findings Present findings may open new avenue in testing whether DCI may have clinical application in endometriosis therapy. Trial registration number Not Applicable

P-329 Oocyte donation outcomes in endometriosis patients with multiple IVF failures

Abstract Study question What are the reproductive outcomes and the prognostic factors of live birth rates in endometriosis patients referred to oocyte donation after multiple in vitro fertilization(IVF)-failures? Summary answer In this specific population, oocyte donation appears to be a viable option to optimize the reproductive outcomes, as the cumulative live birth rate reaches 63.2%. What is known already Assisted Reproductive Technology(ART) is currently recognized as one of the main therapeutic options to manage endometriosis-related infertility, often resulting in satisfactory outcome. A burning issue in this field remains how to deal with patients undergoing recurrent ART failures. As there appear to be two main factors contributing to the failures, i.e., a deleterious effect of endometriosis on embryo implantation and altered oocyte and embryo quality, two competing therapeutic strategies can be considered:(i) endometriosis surgery and (ii) oocyte donation. However, no data has been published to date in the specific population of endometriosis patients with previous IVF failures, undergoing oocyte donation. Study design, size, duration Observational cohort study including fifty-seven women with endometriosis-related infertility and multiple IVF failures (≥ 2 failed IVF cycles) referred to oocyte donation who consulted at our institution between January 2013 and June 2022. Participants/materials, setting, methods Endometriosis was diagnosed based on published imaging criteria using transvaginal sonography and magnetic resonance imaging and confirmed histologically in women who had a history of surgery for endometriosis. The main outcomes measured were the clinical pregnancy rate (CPR) and the cumulative live birth rate (CLBR). We compared the characteristics of women who had a live birth versus those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. Main results and the role of chance Fifty-seven patients underwent 90 oocyte donation cycles, after 244 failed autologous IVF cycles. The mean age of the population was 36.8 ± 3.3 years, with a mean infertility duration of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial endometriosis, 2 patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, the CPR and the CLBR per patient were 49/57 (85.9%) and 36/57 (63.2%), respectively. After multivariate analysis, only being nulligravida (p = 0.002) remained an independent negative predictive factor of the live birth rate. Limitations, reasons for caution In 35.1% of patients there was no surgical/histological proof of endometriosis. However, for all the study participants, endometriosis was diagnosed and staged using patient interviews, clinical examination, and imaging techniques to assess for endometriosis phenotypes, which is in line with the structured diagnostic process acknowledged as being appropriate for endometriosis. Wider implications of the findings In this specific population, poor embryo quality may be the main limiting factor of ART success rates, rather than impaired endometrial receptivity. These data are reason for clinicians not to systematically refer infertile endometriosis patients with recurrent IVF failures to surgery. Trial registration number not applicable