Severe Endometriosis Research Articles

MRI markers of adenomyosis severity associated with worse IVF/ICSI outcomes

Study objective: The aim of this study was to characterise the severity of adenomyosis on MRI in infertile women, and to assess if MRI characteristics of adenomyosis severity are associated with worse IVF/ICSI pregnancy outcomes versus male infertility controls. Materials and methods: This single-centre retrospective study was carried out at Catharina Hospital in Eindhoven, The Netherlands. The MRIs of 124 infertile women undergoing their first, fresh embryo transfer during IVF/ICSI, diagnosed with adenomyosis only ( N = 31), or combined adenomyosis and endometriosis ( N = 93) were assessed. Measurements of MRI adenomyosis features were performed by two independent investigators. IVF/ICSI outcomes (biochemical pregnancy (BP), ongoing pregnancy (OP) and live birth (LB)) of adenomyosis patients were compared to those of 889 male infertility controls. Results: Patients with adenomyosis had significantly worse IVF/ICSI outcomes compared to male infertility controls. When assessing individual MRI parameters, adenomyosis patients with a mean junctional zone (JZ) of >12 mm, a JZ/Myometrium ratio of >40%, presence of myometrial cysts and presence of endometriosis (specifically deep invasive endometriosis(DIE)) showed statistically significantly worse outcomes compared to patients with milder disease. Conclusion: The results of this retrospective study suggest that individual MRI markers for severe adenomyosis (mean JZ > 12 mm, myometrial cysts), especially when combined with (severe) endometriosis, may be associated with fewer pregnancies during IVF/ICSI when compared to male infertility controls. Future prospective studies should investigate the prognostic potential of these markers for prediction of IVF/ICSI success.

Life-time experience of violence as a risk factor for symptomatic endometriosis

The aim of this questionnaire study is to investigate the impact of life-time experiences of violence on the course and severity of endometriosis at a University Endometriosis Center. It also explores women’s attitudes toward medical screening for violence. The questionnaire covered demographic data, medical data, information involving possible experiences of psychological, physical, sexual, and intimate partner violence as well as violence screening in medical care. Questionnaires of 118 participants were analyzed. 41/118 women reported some form of violence (34.8%). These women had a significantly higher risk for severe dysmenorrhea, use of analgesics, and comorbidities in comparison to women without life-time experiences of violence. Statistically significant differences were also found for employment status and impaired working ability. More than 60% of women considered the aspect of violence as important for health. However, only 17.1% of women with experiences of violence recalled being asked about violence by a medical professional. The study results suggest that experiences of violence have a significant impact on the course and severity of endometriosis. The findings highlight the importance of healthcare providers to be aware of the potential impact of violence on women’s health, and routine screening for violence in medical care, especially in women with endometriosis.

Correlations between endometriosis, lipid profile, and estrogen levels.

To explore the association between serum lipids and the occurrence and development of endometriosis using a retrospective review of clinical data. A total of 177 patients who underwent laparoscopic or open surgery due to benign ovarian masses, 117 patients with endometriosis (53 stage III and 64 stage IV), and 60 patients with benign ovarian masses without endometriosis were selected from the gynecology department of Maternal and Child Health Hospital of Hubei Province, between January 1, 2020, and October 30, 2022, to search for endometriosis occurrence by retrospectively analyzed the patients clinical data Risk factors for development and to explore the relationship between blood lipids and endometriosis. The scores of estradiol (E2), carbohydrate antigen 125 (CA125), and pain in the endo - and non-endometriosis groups were significantly different (P < .05), but there was no significant correlation between these 3. There were significant differences (P < .05) in E2, triglyceride (TG), CA125, and the size of the masses between patients with stage III and IV endometriosis. TG, E2, and CA125 were found to be valuable as separate indicators for the prediction of endometriosis, and the 3 indicators could improve the accuracy of the diagnosis of endometriosis when combined. Triglycerides may be positively correlated with the severity of endometriosis. The combination of TG, E2 and CA125 can improve the accuracy of the diagnosis of endometriosis staging.

Transvaginal sonography and surgical findings in the diagnosis of endometriosis individuals: A cross-sectional study.

Endometriosis is a challenging gynecological disease and a debilitating condition that profoundly affects the individual's quality of life. Besides pathological confirmation, diagnostic laparoscopy has been internationally accepted as the standard method to identify the accurate mapping of endometriosis. Transvaginal sonography (TVS) is the first non-invasive imaging modality to estimate the severity of endometriosis. This study aimed to evaluate the accuracy of TVS in affected women compared with surgical findings. This retrospective cross-sectional study surveyed 170 women with deep infiltrating endometriosis (DIE) referred to the endometriosis part of the Avicenna Infertility Center, Tehran, Iran and they underwent TVS followed by laparoscopy. Recorded data of individuals under study in the medical database system were reviewed. Finally, the agreement rate was calculated for ultrasound reports and intraoperative (IO) findings regarding ovarian endometrium, ovarian adhesion, involvement of cul-de-sac, rectovaginal septum, and bowel and ureter. 170 women with DIE entered the study. The agreement of TVS and IO findings were 86.76% for left ovarian endometriosis and 70.86% for right ovarian endometriosis, 93.90% for left ovarian adhesion, and 88.90% for right ovarian adhesion, 88.90% for a cul-de-sac, and 84.82% for bowel nodules. The findings, based on a laparoscopic assessment of the pelvic floor, were completely compatible with ultrasound reports (100%). TVS allows a preoperative evaluation in planning the surgical policy associated. TVS is beneficial for dedicated mapping of DIE; thus, an expert radiologist can aid the surgeon in preoperative evaluation and IO management.

P-655 A prospective, observational, multivariate study to evaluate the best predictor of ovarian response, between AMH measured with fully automated assay and AFC.

Abstract Study question Which of AMH (measured with fully-automated assay) or AFC is the best predictive biomarker of ovarian response to exogenous gonadotropins in IVF/ICSI cycles? Summary answer In patients &amp;gt;35 years, AMH predicts the number of oocytes retrieved better than AFC and it has greater discriminating ability to detect suboptimal response. What is known already Individual variability in ovarian response to a starting dose of gonadotropins is a well-known aspect during controlled ovarian stimulation and many efforts have been made for obtaining the personalization of the treatment, identifying different biomarkers (age, basal FSH, BMI, AMH, AFC) that may predict the ovarian response. Among these biomarkers, AMH and AFC demonstrated the best performance in predicting ovarian response. Nevertheless, approximately one in five patients in clinical practice has a discordance between AMH and AFC; in these cases, the clinicians do not know which indicator should be chosen to individualize the protocol and the starting dose of gonadotropins. Study design, size, duration This prospective, observational, multivariate study compared fully-automated AMH with AFC in the prediction of ovarian response, defined as the number of oocytes retrieved and it involved 161 couples attending their first IVF/ICSI cycle between 2019 and 2022 (ClinicalTrials.gov NCT04168892). The patients underwent a GnRH antagonist protocol and received a HMG starting dose exclusively based on their age (150 IU if ≤ 35 years, 225 IU if &amp;gt; 35 years). Two physicians performed all the AFC determinations. Participants/materials, setting, methods The study was conducted at ANDROS Day Surgery Clinic, Palermo, Italy. Inclusion criteria were: female age 18-40 years, BMI 18-30 kg/m2, FSH ≤15 IU/l, normal menstrual cycles, normal uterine cavity, presence of both ovaries. Exclusion criteria were: PCOS, severe endometriosis, previous ovarian surgery, ovarian cysts, endocrinological diseases. Considering a power (1-β) of 90% and an alpha of 0.01, a total sample size of 160 couples was considered sufficient to verify the study hypothesis. Main results and the role of chance Three out of 161 patients were excluded after randomization. Eighty-eight out of 158 patients (55.7%) received 150 IU as starting dose (age=31.03±3.33; range 21-35 years); 70 patients (44.3%) received 225 IU (age=37.68±1.31, range 36-40). 9/158 cycles (5.6%) were suspended for hypo-response. The two groups were different in number of oocytes retrieved (p &amp;lt; 0.05), with higher number in ≤ 35 years group (M≤35=11.30±7.14, M&amp;gt;35=8.77±5.30). Univariate analyses revealed that the number of oocytes retrieved was correlated, in both groups, with AMH (ps &amp;lt; 0.01) and AFC (ps &amp;lt; 0.01), and in ≤ 35 years group with basal FSH (p = 0.03). No relationships were found with cause of infertility, BMI, smoking. Correlation coefficient (ρ) between AMH and AFC was 0.74 (p &amp;lt; 0.01) in ≤ 35 years group and 0.57 (p &amp;lt; 0.01) in &amp;gt; 35 years group. Multivariate Poisson regressions confirmed that AMH and AFC significantly predicted the number of oocytes retrieved in ≤ 35 years group (p &amp;lt; 0.01, Exp(B)=1.08; and p &amp;lt; 0.01, Exp(B)=1.03, respectively), while only AMH was a significant predictor in &amp;gt; 35 years group (p &amp;lt; 0.01, Exp(B)=1.18) (AFC: p = 0.34, Exp(B)=1.01). For prediction of suboptimal ovarian response (&amp;lt;8 oocytes retrieved), ROC analysis showed that AMH was not different from AFC in ≤ 35 years group (AUCAMH=0.811, AUCAFC=0.767; p = 0.331) but significantly better in &amp;gt; 35 years group (AUCAMH=0.858, AUCAFC=0.675; p &amp;lt; 0.001). Limitations, reasons for caution This is a single-center study; a multicenter trial could be useful for a further validation of the results. Moreover, many laboratories do not use automated assays for measuring AMH and this could make the results of this study hardly applicable in all contexts. Wider implications of the findings The results of this prospective trial highlight that, in patients &amp;gt;35 years, automatized AMH predicts the ovarian response better than AFC and it shows greater discriminating ability to detect suboptimal response. This could open new possibilities of individualizing treatment with AMH-based algorithms, especially in patients with the worst reproductive prognosis. Trial registration number NCT04168892

P-671 Comparing clomiphene citrate/ flexible GnRH antagonist vs ultrashort flare GnRH agonist protocols for controlled ovarian stimulation in poor ovarian reserve patients

Abstract Study question How do Clomiphene citrate (CC)/ flexible GnRH antagonist and ultrashort flare GnRH agonist protocols compare in poor ovarian reserve patients (POSEIDON groups 3 &amp; 4)? Summary answer In poor ovarian reserve patients, irrespective of age, use of CC / flexible antagonist vs ultrashort flare protocol significantly reduces gonadotrophin consumption and stimulation duration. What is known already Poor responders constitute 47% of ART patients and up to 65% of these have diminished ovarian reserve. Despite the various treatment options available, lack of good quality evidence to enable recommendation of a particular protocol or adjuvant continues to pose a challenge to their effective management. The need for multiple stimulations for pooling up embryos also makes effective cost of treatment an added concern in them. Study design, size, duration An open label, multi centric, randomized controlled study was conducted over a period of 1 year recruiting 116 women having AMH &amp;lt;1.2ng/dl and antral follicle count (AFC) &amp;lt;5 who were further analysed in POSEIDON 3 and 4 subgroups. Patients were randomized to 1 of 2 groups for controlled ovarian stimulation. Those with severe endometriosis, adenomyosis, autoimmune or metabolic disorders, sustained hyperprolactinaemia, congenital uterine malformations and with male partners having severe oligoasthenoteratozoospermia were excluded. Participants/materials, setting, methods Group A (55 women) received CC 100mg from D1-D5 with 300 IU human menopausal gonadotrophin (hMG) in a flexible GnRH antagonist protocol. Group B (61 women) underwent ultrashort flare protocol. 1mg leuprolide was administered from D1-D4 and 300 IU hMG given D2 onwards followed by flexible GnRH antagonist administration. Dual trigger with triptorelin and recombinant hCG was administered 35-36 hours before oocyte retrieval. Embryos cultured till D5 were vitrified for transfer at a later stage. Main results and the role of chance The two groups were well matched for baseline characteristics like age, BMI, AMH, duration of infertility, D2 AFC, estradiol and FSH levels. The mean total gonadotrophin consumption (3387.29 + 1082.5 vs 4407 + 1224.2, p value &amp;lt;0.01) and the duration of stimulation (10.71 + 2.52 vs 11.95 + 2.43, p value &amp;lt;0.01) were significantly lower in group A vs group B. The primary outcomes of median number of oocytes retrieved (4 vs 4, p value- 0.71) , M2 rate (3 vs 3, p value-0.91), fertilisation rate were similar in the two groups. The secondary outcomes of oocyte retrieval rate (103.05 + 42.97 vs 97.14 + 42.96, p value- 0.63), FORT (0.81 +0.68 vs 0.96 + 0.48, p value- 0.37) FOI (0.91 + 0.55 vs 0.92+ 0.54, p value 0.92), top quality embryo rate (0.53 + 1.1 vs 0.41 + 0.84, p value 0.61), cycle cancellation rate (26.22% vs 29.09%), implantation rate (23.63% vs 24.59%) and clinical pregnancy rate (21.31% vs 20%) were also similar in group A vs B respectively. A subgroup analysis of POSEIDON 3 versus POSEIDON 4 patients revealed similar outcomes with both the protocols in the two groups. Limitations, reasons for caution Small sample size of the cases limits the current statistical power of the study. Wider implications of the findings CC /flexible GnRH antagonist protocol is an effective alternative to ultrashort flare protocol in patients with poor ovarian reserve irrespective of their age. The lower gonadotrophin dosage required and shorter duration of stimulation observed make it a viable option in patients who might need multiple stimulations for pooling up embryos. Trial registration number Not applicable

P-323 Associations between endometrial microbiome and the local immune cell composition during the mid-secretory phase

Abstract Study question Is there an association between the endometrial microbiome and the local immune cell composition during the mid-secretory phase? Summary answer The percentage of endometrial neutrophils was negatively related to the highest number of microorganisms, while B-cells and T-helpers were positively related to certain bacterial taxa. What is known already Endometrial receptivity is strongly influenced by the local immune cell composition and its inflammatory status. Meanwhile, many studies on the endometrial microbiome and its impact on receptivity are arising. Knowing that bacterial composition has an effect on the immune system, it is worth studying the potential associations between the microbiome and immune cell populations in the endometrium during the mid-secretory phase. This relationship could adjust the magnitude of inflammation which has a strong effect on embryo implantation process. Investigations on the endometrial bacterial communities’ effect on the local immune cell composition could be applied in improving assisted reproductive technologies. Study design, size, duration Prospective observational study performed between April 2021 and January 2023 in a private in vitro hospital. Endometrial biopsies were collected from 30 women aged between 34 and 45 years during the mid-secretory phase, on day 7 after LH surge. Patients with history of recent inflammatory disease, chronic endometritis, recent antibiotic treatment, endocrinological disorders, autoimmune diseases, oncological diseases, moderate or severe endometriosis, adenomyosis, uterine hyperplasia, and endometrial polyps were not included. Participants/materials, setting, methods B cells, T cells, T helpers, NK cells, macrophages and neutrophils in the endometrial stroma were identified by immunohistochemical staining with antibodies against CD79α (IS62, Dako), CD3 (BRB063, Zytomed), CD4 (IS649, Dako), CD56 (А00121-0007, ScyTek), CD14 (Е-AB-71017, Elabscience) and neutrophil elastase (950334, NOVUSBIO), respectively. The immune cell percentages were calculated by HALO image analysis software (version 2.3, IndicaLabs). Endometrial microbiota (EM) composition was analyzed after DNA isolation using 16S rRNA (v4-v5 region) gene sequencing. Main results and the role of chance Totally 271 bacterial species and 668 genera were identified in the endometrial samples. The median (range) immune cell percentages found were: 0.083% (0.49) B-cells, 0.974% (4.93) T-cells, 0.066% (0.44) T-helpers, 0.931% (5.36) NK-cells, 1.129% (3.11) macrophages and 0.207% (3.86) neutrophils. Spearman analysis revealed significant correlations between T-helpers percentage and the relative abundance of Cutibacterium acnes (R = 0.475, p = 0.012) and its genus Cutibacterium (R = 0.477, p = 0.012) as well as between B-cells and the relative abundance of Bacteroides vulgatus (R = 0.532, p = 0.003) and its genus Bacteroides (R = 0.457,p = 0.013). NK-cells presence was not related to any of the found bacterial species or genus (p &amp;gt; 0.05). Neutrophils demonstrated significant correlations with the relative abundance of the highest number of species: Prevotella melaninogenica (R = −0.404, p = 0.03), Butyrivibrio crossotus (R = 0.433,p = 0.02), Moraxella osloensis (R = −0.433, p = 0.019), Blautia sp. (R = 0.427, p = 0.021), Alicyclobacillus acidocaldarius (R = −401,p = 0.031) also related with the T-cells percentage (R = −0.380, p = 0.042) and Acinetobacter lwoffii (R = −0.458, p = 0.008) also related with the macrophages (R = −0.454, p = 0.013). Among the studied species Alloprevotella tannerae was showing significant correlations with neutrophils (R = −0.0602, p = 0.001), macrophages (R = −0.416, p = 0.025) and T-cells (R = −0.464, p = 0.011). At genus level, most of the bacteria were related to the neutrophils – Pseudoalteromonas (R = −0.540, p = 0.002), Aliterella (R = −0.617, p&amp;lt;0.001), Endhydrobacter (R = −0.433,p = 0.019) and AKIW781 (R = −0.493, p = 0.011). Aliterella and AKIW781 were also related to the macrophages (R = −0.473, p = 0.01 and R = −0.423, p = 0.031, respectively) and T-cells (R = −0.387, p = 0.038 and R = −0.519, p = 0.007, respectively). Limitations, reasons for caution The study was limited in sample size. Wider implications of the findings The results of this study indicated that there is a quantitative relation between the main endometrial immune cells and the endometrial core microbiome. The association between these two determinants of endometrial receptivity could help in understanding the fine tuning of the endometrium for accepting the embryo. Trial registration number The current research was funded by National Science Fund, Ministry of Education, Bulgaria, Contract № KP-06-N53/14/16.11.2021.

P-715 NGS-based metagenome analysis of endometrial microbiome in women with implantation failure after in vitro fertilization: results of a prospective cohort study

Abstract Study question We aimed to compare the endometrial microbiome between pregnant and non-pregnant women after frozen embryo transfer (FET) with euploid embryos. Summary answer Specific bacteria taxa had significantly higher relative abundance in the endometrium of patients with implantation failure after FET with euploid embryos. What is known already Several studies revealed a significant association between the endometrial microbiome composition, including the abundance of Lactobacilli and pathogen species and the occurrence of implantation failure or miscarriage. However, there is still scarce information about the influence of relative abundance of certain bacteria taxa on the pregnancy outcome in patients with idiopathic infertility and FET. Study design, size, duration In this prospective observational cohort study endometrial biopsies were collected from 30 women aged between 34 and 45 during the mid-luteal phase (LH + 7) in a natural cycle. FET was performed with euploid embryos (after preimplantation genetic testing for aneuploidy (PGT-A)), up to 6 months after the biopsy. The exclusion criteria for the patients were history of recent inflammatory disease, chronic endometritis, recent antibiotic treatment, moderate or severe endometriosis, adenomyosis, uterine hyperplasia, and endometrial polyps. Participants/materials, setting, methods Endometrial microbiota composition was analyzed using 16S rRNA (v4-v5 region) next generation sequencing (NGS). The sequencing data was assigned to bacterial taxonomy and the background-contaminated bacteria were excluded from the analysis. The Student t-test or Mann-Whitney U test for the relative abundance of each bacteria taxa were applied according to normal or not normal distribution of data. A Bonferroni correction was applied to the significant levels obtained. Main results and the role of chance The performed analysis of 30 patients with different clinical outcomes, including no pregnancy (n = 16), clinical pregnancy confirmed by ultrasound (n = 14) revealed differences in the endometrial microbiome composition. Baseline characteristics including age, BMI and duration of infertility were comparable between the studied groups of patients. In total, 271 distinct bacterial species and 668 bacterial genera were identified. The number of unique species, found in non-pregnant women was 62 (22.88%), while in pregnant patients it was 39 (14.39%). Among them, bacteria with high frequency of occurrence such as Cutibacterium granulosum, Isoptericola, Acetomicrobium, Marivivens, Syntrophomonas and Bacteroides were found only in patients with unsuccessful implantation while Bosea was present only in women with successful implantation. Based on the analysis of bacteria relative abundance, Lactobacillus was the most prevalent genus in both groups. The abundance of this genus was not significantly different between the studied groups. In contrast, Serratia marcescens, Delftia, Massilia, Glutamicibacter, Lactococcus and Staphyloccocus were significantly enriched in the non-pregnant group (p &amp;lt; 0.05). Limitations, reasons for caution Our study is a single-center study with a relatively small sample size. Wider implications of the findings The microbiome showed specific composition in pregnant compared to non-pregnant women. It could be hypothesized that an appropriate treatment for optimization of endometrial microbiome content in women with diagnosed microbiome dysbiosis could be beneficial for improvement of pregnancy rates. Trial registration number The current research was funded by National Science Fund, Ministry of Education, Bulgaria, Contract № KP-06-N53/14/16.11.2021.

P-317 Associations between endometrial microbiome composition and cellular senescence

Abstract Study question Is there an association between the percentage of senescent cells and microbiome composition in human endometrium? Summary answer We found that cellular senescence is negatively associated with the relative abundance of certain bacterial taxa. What is known already Recent studies indicated that endometrial microbiome characteristics and certain levels of cellular senescence are essential for the establishment of normal endometrial receptivity and successful embryo implantation. The secretion of senescence-associated secretory phenotype (SASP) components is responsible for immune cell activation and might cause endometrial dysbiosis. On the other hand, some studies suggest that the presence of specific metabolic groups of bacteria and their metabolites could influence cellular stress response that might suppress the development of senescent cells. However, the direct relationship between the quantity of senescent cells and microbiome content in the endometrium has never been studied. Study design, size, duration This was a prospective observational cohort study performed between April 2021 and January 2023. Endometrial biopsies were collected from 30 women aged between 34 and 45 during the mid-luteal phase (LH + 7) in a natural cycle. Each biopsy was divided for genetic and immunohistochemical analyses. The exclusion criteria were history of recent inflammatory disease, chronic endometritis, recent antibiotic treatment, endocrinological disorders, autoimmune diseases, oncological diseases, moderate or severe endometriosis, adenomyosis, uterine hyperplasia, and endometrial polyps. Participants/materials, setting, methods We used immunohistochemical biomarker p16ink4a (MAD-000690QD–7, Master Diagnostica) to identify senescent cells. The percentages of positively stained cells in the endometrial stroma and in the luminal epithelium were calculated by HALO image analysis software (version 2.3, IndicaLabs). Endometrial microbiota composition was analyzed after DNA isolation from the endometrial samples using 16S rRNA (v4-v5 region) gene sequencing. Statistical analysis was performed by Spearman’s correlation test using SPSS v.21 (IBM Corp., Armonk, NY, USA). Main results and the role of chance A total of 271 distinct bacterial species and 668 genera were identified across the studied 30 endometrial samples. The percentage of p16+ senescent endometrial stromal cells ranged from 0 to 1.7%, with a mean value of 0.37%, while the percentage of p16+ luminal epithelial cells ranged between 2.5% and 74.0%, with a mean value of 21.5% Spearman analysis revealed significant negative correlation between the percentage of p16+ stromal cells and the relative abundance of Porphyromonas sp. (R = −0.41, p = 0.03) and Sphingobacterium sp. (R = −0.37, p = 0.05). The percentage of p16+ luminal senescent cells correlated negatively with the abundance of Micrococcus luteus (R = −0.44, p = 0.02), Moraxella osloensis (R = −0.37, p = 0.05), Rubellimicrobium sp. (R = −0.46, p = 0.02), Stenotrophomonas sp. (R = − 0.45, p = 0.03), Chryseobacterium sp. (R = −0.41, p = 0.04), Carnobacterium sp. (R = −0.40, p = 0.04), Deinococcus sp. (R = −0.38, p = 0.05), and Enhydrobacter sp. (R = − 0.37, p = 0.05). Limitations, reasons for caution The study was limited in sample size. The assessment includes only endometrial samples from the mid-luteal phase of the cycle. Wider implications of the findings We found that the level of senescence is negatively associated with the relative abundance of certain bacteria taxa in human endometrium, including some related to impaired reproductive function and early embryonic development arrest. These findings suggest a possible specific interaction between senescent cells and microbiome that might influence endometrial receptivity. Trial registration number The current research was funded by National Science Fund, Ministry of Education, Bulgaria, Contract № KP-06-N53/14/16.11.2021

Uterine junctional zone and adenomyosis: comparison of MRI, transvaginal ultrasound and histology.

The uterine junctional zone is the subendometrial area in the myometrium that contributes to peristalsis and aids in spermatozoa and blastocyst transport. Alterations in the appearance of the junctional zone on transvaginal sonography (TVS) or magnetic resonance imaging (MRI) are associated with adenomyosis. The lack of standardization of description of its appearance and ill-defined boundaries on both histology and imaging hamper understanding of the junctional zone and limit its role in the diagnosis of adenomyosis. The objectives of this review were to investigate the accordance in definition of the junctional zone across different diagnostic approaches and to examine how imaging findings can be linked to histological findings in the context of diagnosis of adenomyosis. A comprehensive literature review was conducted of articles describing the appearance on imaging and the histological structure of the uterine junctional zone. Our review suggests that the junctional zone is distinguished from the middle and outer myometrium by gradual changes in smooth-muscle cell density, extracellular space, connective tissue, water content and vascular properties. However, while the signal intensity from the junctional zone to the middle myometrium changes abruptly on MRI, the histopathological changes are gradual and its border may be difficult or impossible to distinguish on two-dimensional TVS. Moreover, the thickness of the junctional zone measured on MRI is larger than that measured on TVS. Thus, these two imaging modalities reflect this zone differently. Although a thickened junctional zone is often used to diagnose adenomyosis on MRI, the presence of adenomyosis can be described more accurately as interruptions of the junctional zone by endometrial tissue, which leads to direct signs on imaging such as subendometrial lines and buds on two- and three-dimensional TVS or bright foci on MRI. The histopathological criteria for diagnosis are based on enlargement of the uterus with severe adenomyosis, and might not reflect its early stages. Clinicians should be aware that findings on MRI cannot be extrapolated readily to ultrasound. An understanding of this is necessary when investigating the uterine junctional zone as a functional unit and the association between visualization of direct features of adenomyosis in the junctional zone and clinical symptoms. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Long-term risk of repeated surgeries in women managed for endometriosis: a 1,092 patient-series

To assess the long-term risk of repeated surgery in women undergoing complete excision of endometriosis by an experienced surgeon and to identify circumstances leading up to repeat surgery. Retrospective study based on data recorded in a large prospective database. University Hospital. A total of 1,092 patients managed for endometriosis, from June 2009 to June 2018, by one surgeon. Complete excision of endometriosis lesions. The recording of a repeated surgery linked to endometriosis performed during follow-up. Endometriosis was exclusively superficial in 122 patients (11.2%) and 54 women (5%) had endometriomas without associated deep endometriosis nodules. Deep endometriosis was managed in 916 women (83.9%), leading to infiltration or not of the bowel in 688 (63%) and 228 (20.9%) patients, respectively. A majority of patients were managed for severe endometriosis infiltrating the rectum (58.4%). Mean and median follow-up was 60 months. A total of 155 patients underwent a repeated surgery relating to endometriosis; 108 procedures were required because of recurrences (9.9%), 39 surgeries were related to the management of infertility by assisted reproductive techniques (3.6%), and in 8 surgeries, a direct relationship between surgery and endometriosis was probable but not certain (0.8%). The majority of procedures involved hysterectomy for adenomyosis (n=45, 4.1%). The probability of requiring repeated surgery at 1, 3, 5, 7, and 10 years was 3%, 11%, 18%, 23%, and 28%, respectively. Cox's multivariate model identified postoperative pregnancy and hysterectomy as being statistically significant independent predictors for a reduction in the probability of having a repeated surgery, after adjustment on continuous postoperative amenorrhea, the main localization of the disease, and management for endometriosis infiltrating the rectum during the first surgery. Up to 28% of patients may require a repeated surgical procedure during the 10 years after complete excision of endometriosis. Conservation of the uterus is followed by an increased risk of repeated surgery. The study is based on outcomes resulting from a single surgeon, which limits the generalizability of results.

Natural progression of deep pelvic endometriosis in women who opt for expectant management.

The natural history of endometriosis is poorly understood, and despite numerous studies, the rate of the disease progression and optimal treatment planning in women who are asymptomatic or experience mild symptoms not requiring treatment are unknown. The aim of this study was to assess the behavior of deep endometriosis in women who are managed expectantly without any medical or surgical intervention. A retrospective cohort study of women diagnosed with deep endometriosis on transvaginal ultrasound scan at the Department of Gynecology, University College London Hospitals and The Gynecology Ultrasound Centre, London, UK, from April 2007 to April 2022. All women attended for at least two ultrasound scans which were carried out by a single expert ultrasound examiner and at least 6 months apart. The number and position of endometriotic nodules were recorded, and the mean diameter of each nodule was calculated from measurements taken in three orthogonal planes. During the study period, 1922 women were found to have moderate or severe deep endometriosis on pelvic ultrasound examination. A total of 135 premenopausal women who were managed expectantly fitted the inclusion criteria. The median number of endometriotic nodules per woman at the initial visit was 2 (range: 0-7), and the median follow-up time was 666 days (181-2984). In the follow-up period, 50/135 women (37%, 95% CI: 29-46) developed additional nodules or experienced an increase in nodule size, and 17/135 women (13%, 95% CI: 8-19) had a regression in the number or size of the nodules. In the remaining 68/135 women (50%, 95% CI: 42-59) the disease remained static during the follow-up. The median change in mean diameter of nodules during the study period per woman was +0.13 mm (-11.67 - +5.83), with an annual growth rate of +0.09 mm/year (-6.65 - +6.45). In our study we found evidence of deep endometriosis progression in just over a third of women. In view of this, asymptomatic or mildly symptomatic women diagnosed with deep endometriosis could be reassured that their disease is unlikely to worsen with time.

The Relation between Patient-Centered Care and Quality of Life in Women with Endometriosis

Objective: The objective of this study was to examine the hypothesis that experiences with patient-centered endometriosis care are related to the endometriosis-specific quality of life dimensions “emotional well-being” and “social support.” Design: A secondary regression analysis of two cross-sectional studies was conducted. Participants/Materials: In total, data from 300 women were eligible for analysis. The participating women all had surgically proven endometriosis. Setting: The study was conducted in one secondary and two tertiary endometriosis clinics in the Netherlands. Questionnaires were disseminated between 2011 and 2016. Methods: Both included studies investigated patient-centeredness of endometriosis care and endometriosis-specific quality of life using, respectively, the ENDOCARE questionnaire (ECQ) and the Endometriosis Health Profile 30 (EHP-30). To increase power, the regression analysis focused on the previously found relation between the ten dimensions of the ECQ and the EHP-30 domains “emotional well-being” and “social support” rather than all five EHP-30 domains. After the Bonferroni correction to limit type 1 errors, the adjusted p value was 0.003 (0.05/20). Results: The participating women had a mean age of 35.7 years and had predominantly been diagnosed with moderate to severe endometriosis. None of the relations between patient-centered endometriosis care and the EHP-30 domain “emotional well-being” were significant. Three dimensions of patient-centered endometriosis care proved to be significantly related to the EHP-30 domain “social support”: “information, communication, and education” (p < 0.001, beta = 0.436), “coordination and integration of care” (p = 0.001, beta = 0.307), and “emotional support and alleviation of fear and anxiety” (p = 0.002, beta = 0.259). Limitations: This cross-sectional study identified relations rather than proving causality between experiencing less patient-centeredness of care and having lower quality of life. Nevertheless, it is very tangible that some causality exists, either directly or indirectly (e.g., through empowerment) and that by improving patient-centeredness, quality of life might be improved as well. Conclusion: “Information, communication, and education”; “coordination and integration of care”; and “emotional support and alleviation of fear and anxiety” as dimensions of patient-centered endometriosis care are related to the quality of life domain “social support” of women with endometriosis. Improving the patient-centeredness of endometriosis care was already considered an important goal, but even more so given its relation with women’s quality of life, which is increasingly considered the ultimate measure of health care quality. Quality improvement projects focusing on “information, communication, and education” are expected to impact women’s quality of life the most.

Serum concentrations of IL-16 and its genetic polymorphism rs4778889 affect the susceptibility and severity of endometriosis in Nigerian women

BackgroundEndometriosis is the presence of active ectopic endometrial glands and stroma at other sites outside the uterine cavity. It is a common cause of chronic pelvic pain which is sometimes debilitating, and inflammation is one of the known triggers of endometriosis. Interleukins 6 and 16 (IL-6 and IL-16) are proinflammatory cytokines which play essential roles in inflammatory diseases. We therefore investigated the relationship between genetic polymorphisms of interleukins 6 and 16, and the development of endometriosis in Nigerian women.MethodOne hundred and thirty (130) consenting women were consecutively enrolled, sixty-five (65) of whom had endometriosis and 65 age-matched women as reference group, surgically confirmed as not having endometriosis. Spectrophotometric determination of serum concentrations of Interleukins 6 and 16 was carried out and the genotyping of IL-6 (rs1800795) and IL-16 (rs4778889, rs11556218, rs4072111) genes were performed using TaqMan assays.ResultsSerum IL-16 concentration was significantly higher in women with severe chronic pelvic pain compared to those with mild pain (p = 0.023). The C allele of rs4778889 was associated with endometriosis (OR: 1.80, 95% CI: 1.08 – 3.02, p = 0.024).ConclusionSerum IL-16 and IL-16 rs4778889 may be important markers for endometriosis in Nigerian, and by extension, African women. Multicentre African studies would clarify this.

Severe Pelvic Endometriosis Involving the Rectum with Near Complete Bowel Obstruction: A Case Report

Severe Pelvic Endometriosis Involving the Rectum with Near Complete Bowel Obstruction: A Case Report

I saw the “kissing ovaries” sign: Too close for comfort

The Kissing ovaries sign is a radiological sign seen in women with deep pelvic endometriosis. It refers to abutment of the ovaries within the cul-de-sac. The term kissing ovaries was first described by Ghezzi et al. (2005) and has been since used widely. When seen on imaging it indicates moderate to severe endometriosis with the ovaries tethered within abnormal pelvic soft tissue, which may warrant surgical management.

Forskolin versus cAMP-Induced Decidualization and Survival of Endometrial Stromal Cells of Endometriosis Patients.

Impairment of decidualization of eutopic human endometrial stromal cells (hESCs) may cause an increase in cell survival of endometrial tissue in the peritoneal cavity constituting a precondition for endometriosis development. Decidualization is a physiological process involving progesterone action and cAMP signaling. We here evaluated the effect of 8-Br-cAMP, the adenylate cyclase activator forskolin and of the progestin progesterone and medroxyprogesterone acetate (MPA) alone and in combination on decidualization induction using prolactin ELISA, and on cell size, cell granularity, and cell survival via flow cytometry in hESCs of patients with and without endometriosis. While progestins alone did not induce functional decidualization in hESCs, 8-Br-cAMP and forskolin induced decidualization in hESCs from both cohorts, whereas the induction of FOXO1 transcription and prolactin secretion by forskolin was significantly lower than by 8-Br-cAMP. 8-Br-cAMP- and forskolin-induced prolactin secretion was significantly enhanced by MPA, but not by progesterone. Decidualization entailed a decrease in cell size and in cell granularity. In general, hESCs from women with mild (ASRM I/II) as well as severe (ASRM III/IV) endometriosis in trend displayed a higher granularity, whereas mainly hESCs from severe endometriosis showed a stronger resistance to the induction of cell death after decidualization induction. In both cohorts, the amount of the decidual marker protein prolactin rather exhibited an anti-proportional correlation to cell death induction during six day treatment. This study contributes to widen our understanding of the connection of decidualization and cell death in endometriosis.

MP30-19 HUMAN SPERM IGF2 mRNA LEVELS INVERSELY CORRELATE WITH EMBRYO GROWTH VELOCITY DURING EARLY STAGE OF EMBRYO DEVELOPMENT

You have accessJournal of UrologyCME1 Apr 2023MP30-19 HUMAN SPERM IGF2 mRNA LEVELS INVERSELY CORRELATE WITH EMBRYO GROWTH VELOCITY DURING EARLY STAGE OF EMBRYO DEVELOPMENT Rossella Cannarella, Scott Lundy, Nina Desai, Sarah Vij, and Aldo E. Calogero Rossella CannarellaRossella Cannarella More articles by this author , Scott LundyScott Lundy More articles by this author , Nina DesaiNina Desai More articles by this author , Sarah VijSarah Vij More articles by this author , and Aldo E. CalogeroAldo E. Calogero More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: IGF2 is a potent growth factor capable of influencing cell division and modulating numerous cellular functions. IGF2 mRNA has been identified in human spermatozoa, but little is known about its function in in early embryo development. The aim of this study is to evaluate whether IGF2 levels in spermatozoa is associated with early growth kinetics of human embryos in couples undergoing ICSI. METHODS: This study was conducted on patients undergoing ICSI treatment with fresh oocytes and fresh ejaculated spermatozoa. Couples with infertility due to suspected female factor (e.g., impaired oocyte quality as in patients with severe endometriosis and premature ovarian failure) were excluded from the study. Following clinical use, a surplus aliquot of the semen sample used for ICSI was used to analyze the levels of IGF2 mRNA. The kinetic parameters of each embryo were correlated with the amount of IGF2 mRNA measured in the same swim-up sperm sample used for ICSI. RESULTS: 16 patients were enrolled and a total of 131 embryos were collected. Patients were divided into two groups based on the βhCG test results. We found no statistically significant difference in IGF2 mRNA levels and embryo morphokinetic parameters between the two groups (Table 1). At the correlation analysis, we found a significant negative correlation between sperm IGF2 mRNA levels and the time of pronuclei (tPN) fading (r= -0.2572, p= 0.0078, n=106 embryos), and between sperm IGF2 mRNA and t2 (r= -0.2368, p= 0.0145, n=106 embryos). In contrast, sperm IGF2 mRNA levels were not significantly correlated with tPN, t3, t4, t5, t6, t7, t8, t9, t morula (tM), t blastocyst (tB), and time of expanded blastocyst (tEB) (Table 1). CONCLUSIONS: These results suggest a role for sperm IGF2 mRNA in the very early embryo development (tPN fading -t2). This evidence may help in identify the etiology of apparently idiopathic couple infertility. Indeed, since prolonged t2 has been associated with a poor chance of embryo development into a viable blastocyst, a low level of sperm IGF2 mRNA level can delay t2 and lead to no blastocyst formation. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e398 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rossella Cannarella More articles by this author Scott Lundy More articles by this author Nina Desai More articles by this author Sarah Vij More articles by this author Aldo E. Calogero More articles by this author Expand All Advertisement PDF downloadLoading ...

KRAS mutations and endometriosis burden of disease.

The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p=0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p=0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR]=1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR=0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR=1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.

Total laparoscopic hysterectomy when there is posterior cul-de-sac obliteration: a step-by-step nerve-sparing technique

Dense adhesions due to severe endometriosis between the posterior cervical peritoneum and the anterior sigmoid or rectum obliterate the cul-de-sac and distorts normal anatomic landmarks. Surgery for endometriosis is associated with severe complications, including ureteral and rectal injuries as well as voiding dysfunction. Surgeons should recognize the importance of not only avoiding ureteral and rectal injuries but also focusing on the preservation of the hypogastric nerves. We herein report the anatomical highlights and surgical steps of laparoscopic hysterectomy for posterior cul-de-sac obliteration with the nerve-sparing technique.