Stage Of Endometriosis Research Articles

Is vagus nerve-mediated regulation of immunity an etiological target for therapeutic intervention in endometriosis?

Endometriosis is a complex chronic neuro-inflammatory disorder, affecting roughly 10% of reproductive-age women. It is characterized by the presence of endometrial-like tissue outside the uterus, which induces a chronic inflammatory reaction. This disease can present a wide range of symptoms, including chronic pain and infertility. Despite extensive research, the exact pathogenesis of endometriosis remains incompletely understood. New strategies and paradigms on pathogenesis and treatment are needed. Schematic factors contributing to the development of endometriosis lesions include genetic, hormonal, and immunological factors. Although genetics may contribute to the epidemiologically suggested heritability of endometriosis, epigenetics has gained an increasing consideration in research. Remarkably, microbiota dysbiosis, acting as a catalyst for the main acknowledged epigenetic etiologies (locally produced estradiol, pro-inflammatory cytokines, and hypoxic stress) demands further attention. Indeed, over the past 10 years, it has become clear that the vagus nerve, the fastest component of the microbiota-gut-brain axis, can efficiently control inflammation through the cholinergic anti-inflammatory pathway. Therefore, stimulation of the vagus nerve could be a good candidate for modulating the severity of endometriosis. The detrimental consequences of microbiome dysbiosis and the estrobolome activity on the initiation of the disease as well as counterpart dysfunctions in the central nervous system will be focused on, both supporting a key role of the vagus nerve since the early stage of endometriosis. Consequently, the rationale for using non-invasive vagus nerve stimulation will be discussed, introducing a fruitful shift of paradigm in this still enigmatic disease.

Retinoic acid receptor alpha expression in endometrioid heterotopias and the endometrium of patients with endometriosis

BACKGROUND: Vitamin A is a fat-soluble compound, which is a biologically inactive food form and undergoes transformation by cytosolic alcohol dehydrogenases and microsomal retinol dehydrogenases into retinaldehyde, followed by oxidation by retinaldehyde dehydrogenases 1, 2 and 3 into retinoic acid. All-trans-retinoic acid has been identified as an active metabolite of retinoic acid, indirectly participating in various processes: differentiation, proliferation and apoptosis. Based on a number of studies, the role of retinoic acid and its receptors in various diseases has been proven. For example, the destruction of the RAR-β gene by the integration of the hepatitis B virus into its loci can be a factor in the development of human hepatocellular carcinoma. Subsequently, it was described that the characteristic point of interruption of translocation t(15:17), observed in acute promyelocytic leukemia, was located at the locus encoding retinoic acid receptor-α. As a result, in patients with acute promyelocytic leukemia, complete remission of the disease could often be achieved by treatment with high doses of all-trans-retinoic acid. Existing data on the ability of retinol to influence the processes of differentiation, proliferation, and apoptosis indicate that retinol may be involved in the pathogenesis of endometriosis, but the mechanisms of its effect on the disease are subject to further study. AIM: The aim of this study was to evaluate the retinoic acid receptor alpha expression in endometrioid heterotopias and the endometrium of patients with different endometriosis stages according to the Revised American Society for Reproductive Medicine classification. MATERIALS AND METHODS: This was a prospective study to determine the retinoic acid receptor alpha expression in the endometrium and endometrioid heterotopias of patients with endometriosis (n = 28) and of the control group (n = 10). RESULTS: The retinoic acid receptor alpha expression in endometrioid heterotopias was lower compared to the eutopic endometrium of patients with endometriosis and the endometrium of patients in the control group by 3.4 and two times, respectively (p 0.001; the Kruskal – Wallis method). CONCLUSIONS: The data obtained indicate the involvement of retinol in the pathogenesis of endometriosis. Despite the relative increase in retinol level in the peripheral blood and peritoneal fluid in patients with endometriosis compared to the control group, shown in our previous studies, the reduced retinoic acid receptor alpha expression in endometrioid heterotopias does not allow for full binding of vitamin A to the receptor and is accompanied by its improper metabolism.

Surgical Enhancement with the Placement of Temporary Bilateral Ureteral Stents with Indocyanine Green Injection for all Stages of Endometriosis in vNOTES: Retrospective Cross-Sectional Study

Study ObjectiveTo demonstrate the time to place temporary bilateral stents with indocyanine green (ICG) injection, time to intra-operative identification of bilateral ureters - with and without the use of ICG, and number of times for ICG activation in endometriosis excision surgery. DesignRetrospective cross-sectional study. SettingSingle Tertiary Academic Hospital. PatientsFifty serial patients with functioning pelvic ureters, who underwent vaginal natural orifice transluminal endoscopic surgery (vNOTES) for all stages of endometriosis excision between September 2023 and May 2024. InterventionsPlacement of temporary bilateral ureteral stents with indocyanine green injection before the start of vNOTES, noting the time needed to identify intra-peritoneal ureters with and without ICG activation, and average number of times ICG was activated for endometriosis excision. Measurements and Main ResultsThe median time to place bilateral ureteral stents with ICG injection was 229 seconds. The median time for intra-operative ureteral identification with ICG was 1s (L) and 1s (R). The median time for intra-operative ureteral identification without ICG was 17s (L) and 17s (R). The median time ICG was activated for ureteral identification to perform endometriosis excision was 12 times (L), 11 times (R). From the observations previously described, we share the potential of improved efficiency and efficacy in using ICG in ureteral identification for endometriosis surgery. ConclusionPlacement of temporary bilateral ureteral stents with ICG has the potential for more efficient ureteral identification even after including time for ureteral stent placement and ICG injection. The upfront time needed to place stents may prove to lead to a safer, more efficient procedure.

Intra-operative and post-operative complications of endometriosis excision using the SOSURE approach - A single- surgeon retrospective series of 1116 procedures over 8 years.

Endometriosis surgery outcomes have been widely studied, yet heterogeneity in terminology and techniques persist. This study focuses on the perioperative outcomes of a single surgeon using the same structured approach (SOSURE: Survey & Sigmoid mobilisation, Ovarian mobilisation, Suspension of uterus and ovaries, Ureterolysis, Rectovaginal and pararectal space development, Excision of all visible disease) and adheres to the recent standardised terminology proposed by international gynaecological and endometriosis societies. A quality improvement study was conducted retrospectively from January 2015 to January 2023. Data collection involved two databases: the National British Society for Gynaecological Endoscopy (BSGE) database and a more comprehensive locally kept database. The methodology also integrated four endometriosis staging systems. Intra-operative and post-operative complication rates. Between 2015 and 2023, 1047 women underwent 1116 endometriosis procedures in various UK hospitals with S.K. as primary surgeon. Exclusions totalled 20 due to missing records and specific surgical criteria. The rate of major post-operative complications (Clavien-Dindo grade 3a and 3b) was 1.5% and minor post-operative complications (Clavien-Dindo grade 1 and 2) were seen in 13.8%. No Clavien-Dindo grade 4 or 5 complications were noted. Our study has shown a low complication rate in endometriosis surgery, despite increasing complexity of surgical cases. This is likely attributed to the surgeon's learning curve, high surgical volume and adherence to a structured approach. Our study demonstrates the learning curve of a surgeon over the course of 8 years. This series involved more than 1000 patients and to our knowledge, is the first to report the complexity of the casemix using four different endometriosis staging systems.

LAPAROSCOPIC DIAGNOSIS OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY

The purpose of the study – to generalize the laparoscopic manifestations of genital andextragenital endometriosis in women with infertility, followed by the determination of itsbelonging to international classifications of pathology for the possibility of choosing fullfledged methods of influencing the focus of the disease.Materials and methods. The study was conducted in two stages: a detailed analysis ofscientific studies on the issue of classification of endometriosis R-AFS, Enzian, EFI witha generalization of the main search criteria during laparoscopy; a study based on themedical center «Yuzko» in Chernivtsi, in which 42 women who contacted about infertilitytook part. In the practical part of the work, clinical and paraclinical methods of diagnosis,laparoscopic revision were used, followed by the formation of diagnoses according to themain classifiers of endometriosis, determination of the fertility index and generalizationof the form of endometriosis as a cause of infertility.Research results. Endometriosis is a chronic pathology of the female reproductive system,which often leads to infertility and is accompanied by various clinical manifestations inthe form of pain and menstrual dysfunction. For the purpose of a complete diagnosis ina specific case, an important stage is the determination of the depth and stage of developmentof the endometrioid focus based on the results of laparoscopy according to the classificationproposed by the American Fertility Society (R-AFS classification), Enzian, followed bythe determination of the fertility index (EFI) in order to choose individual managementtactics of each patient. A study was conducted at Yuzko Medical Center, in which 42 womenof various ages who complained of infertility took part. In the course of laparoscopicoperations, various methods of removing endometrioid foci were implemented depending onthe specific clinical case, after which the stage of endometriosis was determined according to the Enzian, R-AFS classification, and a conclusion was formed about the directdependence of the risk of infertility and the depth of the spread of endometriosis foci.Conclusion. The stage and depth of endometriosis plays a decisive role in the developmentof female infertility, which requires careful diagnosis according to modern classificationsand the implementation of a specific treatment program with the aim of developinga natural pregnancy or successful embryo transfer during in vitro fertilization.

Continued improvement to imaging diagnosis and treatment triage of endometriosis: The role of the multi-disciplinary conference

Patient-centered endometriosis management tailored to the individual patient's subset of symptoms often requires highly sensitive and specific preoperative imaging. In the setting of a present ongoing learning curve among radiologists who interpret pelvis ultrasounds and MRIs for diagnosis of endometriosis, we have found that routine feedback between minimally invasive gynecology surgeons and radiologists, based on pre-operative imaging and postoperative laparoscopic findings, is essential for the continual improvement of imaging-based staging of endometriosis and empower pre-operative imaging as an important pillar of endometriosis management. We share illustrative patient cases, which, after collaborative discussion during our routine multi-institutional, multi-disciplinary conferences (MDCs) have led to improved patient counseling, better pre-surgical planning, and therefore improved patient satisfaction. Our endometriosis MDCs will continue to improve patient management in the future by providing a forum for trainees in medical, surgical, imaging, and pathology specialties to gain expertise directly from subspecialists, and participate in the care of these patients.

The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-β) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.

Association between Ovarian Endometriomas and Stage of Endometriosis.

Objectives: To determine the association between ovarian endometriomas and stage of endometriosis. Methods: A total of 222 women aged 18-55 years old, who underwent minimally invasive surgery between January 2016 and December 2021 for treatment of endometriosis were included in the study. Patients underwent laparoscopic and/or robotic treatment of endometriosis by a single surgeon (FRN) and were staged using the ASRM revised classification of endometriosis. Pre-operative imaging studies, and operative and pathology reports were reviewed for the presence of endometriomas and the final stage of endometriosis. Using univariate analyses for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data, association between endometriomas, stage of endometriosis, type of endometrioma, and other patient parameters such as age, gravidity, parity, laterality of endometriomas, prior medical treatment, and indication for surgery was analyzed. Results: Of the 222 patients included in the study, 86 patients had endometrioma(s) and were found to have stage III-IV disease. All 36 patients with bilateral endometriomas and 70% of patients with unilateral endometriomas had stage IV disease. Conclusions: The presence of ovarian endometrioma(s) indicates a higher stage of disease, correlating most often with stage IV endometriosis. Understanding the association between endometriomas and anticipated stage of disease can aid in appropriate pre-operative planning and patient counseling.

Bioconcentration of polycyclic aromatic hydrocarbons in the adipose tissue of women with pelvic endometriosis and idiopathic infertility: A case-control study

PurposePolycyclic aromatic hydrocarbons (PAHs), present in air and food, generated during energy production and waste incineration, are known for health toxicity. PAHs may activate the aryl hydrocarbon receptor, which could in turn modify estrogen-dependent inflammatory pathways in endometriosis. The possible role of PAHs in the pathogenesis of endometriosis remains unclear. The study aimed to evaluate the potential link between exposure to PAHs and the occurrence of peritoneal and ovarian endometriosis. MethodsA prospective case-control tertiary-center study included 46 women aged 22–45 undergoing laparoscopy due to pelvic endometriosis (n ​= ​32; arm 1) and idiopathic infertility (n ​= ​14; arm 2). A sample of the greater omentum was collected intraoperatively for detection of 16 standard PAHs by gas chromatography-isotope dilution mass spectrometry method. PAHs concentrations were compared in both study arms. The associations between PAHs concentrations and selected variables were investigated. ResultsThere were no significant differences between both arms in terms of reference PAHs concentrations, nor correlations between PAHs concentrations and the stage of endometriosis. However, notable differences were observed in specific PAHs concentrations related to certain conditions. The concentrations of acenaphthene (p ​= ​0.016) and fluorene (p ​= ​0.013) were significantly lower in women with peritoneal adhesions, while the concentrations of benz[a]anthracene, benzo[k]fluoranthene and indeno[1,2,3-cd]pyrene [ng/g] were higher in cigarette smokers. ConclusionsThe study showed no differences in exposure to PAHs between women with and without pelvic endometriosis. Determining the toxicity of PAHs in endometriosis requires further research.

O-147 Role of serum progesterone levels and subcutaneous progesterone supplementation in endometriosis patients undergoing artificial cycle frozen embryo transfer

Abstract Study question Is there any impact of serum progesterone levels and subcutaneous progesterone supplementation on live birth rate in endometriosis patients undergoing Artificial Cycle-Frozen Embryo Transfer (AC-FET)? Summary answer Endometriosis patients have comparable progesterone levels before transfer to those without endometriosis. Progesterone supplementation results in similar live birth rate (LBR) to the general population. What is known already Progesterone (P4) resistance is a hallmark of uterine alterations in endometriosis. This disease could disrupt balance between progesterone and estrogen signaling pathways, resulting in estrogen dominance and progesterone resistance at the receptor level, which warrants a deeper exploration for adjusting dosages when performing AC-FET. A recent retrospective study highlights the potential significance of a progesterone threshold when using vaginal and intramuscular progesterone systematically in AC-FET, correlating with a significantly higher LBR for endometriosis-patients. However, no current studies have compared LBR according to P4 the day before blastocyst-transfer and progesterone supplementation in endometriosis versus non-endometriosis-patients undergoing AC-FET with standard vaginal treatment. Study design, size, duration This is a retrospective cohort study including 985 cycles undergoing autologous AC-FET with standard vaginal progesterone treatment (600 mg/day) at a university-affiliated fertility center from January 2019 to December 2022. 168 cycles were from patients with confirmed endometriosis. LBR was evaluated in both groups based on P4 levels the day before transfer. Progesterone supplementation via SC injection (25 mg/day) was administered when levels were deemed low (<10.6 ng/mL based on our previously published research). Participants/materials, setting, methods Endometrial preparation involved oral estrogens at 6 mg daily from the begging of menstrual cycle. Micronized vaginal progesterone (600 mg/day) was added when thickness reached 7 mm. P4 was measured before embryo transfer; supplementation (25 mg SC injection) was added if < 10.6 ng/mL. FET occurred 6 days after initiating luteal phase support. Treatment continued until the pregnancy test. If pregnant, treatment ceased at 10 weeks of amenorrhea. Main results and the role of chance Comparisons between endometriosis and non-endometriosis groups revealed similar baseline characteristics regarding age, BMI, parity, number of embryos transferred, and embryo quality. The number of cycles with levels ≥10.6 ng/mL before transfer were comparable between patients with and without endometriosis (aOR 0.98, 95% CI 0.65-1.47) according to a multivariable logistic regression analysis adjusting for age, BMI, and prior progesterone levels <10.6ng/mL the day before transfer. Unadjusted findings demonstrated equivalent clinical pregnancy, miscarriage, and live birth rates in endometriosis compared to non-endometriosis patients. A subsequent multivariable logistic regression analysis to analyze LBR was conducted, considering four groups: Group 1: Endometriosis with progesterone <10.6ng/mL and SC supplementation (51 patients) Group 2: Endometriosis with progesterone ≥10.6ng/mL (117 patients) Group 3: Non-endometriosis with progesterone <10.6ng/mL and SC supplementation (274 patients) Group 4: Non-endometriosis with progesterone ≥10.6ng/mL (543 patients) Adjusted for age, BMI, and embryo quality, Group 1 was considered as the reference. Results showed comparable live birth rates between the reference group and Group 2 (aOR 0.79, 95% CI 0.36-1.74), Group 3 (aOR 0.91, 95% CI 0.45-1.8), and Group 4 (aOR 1.9, 95% CI 0.71-2.74). Subcutaneous supplementation for endometriosis patients with P4<10.6ng/mL the day before embryo transfer led to similar LBR compared to the other groups. Limitations, reasons for caution The main limitation of this study is the single-center retrospective approach. While the total number of endometriosis patients is 168, the representation of endometriosis patients in group 1 may be a study limitation. Furthermore, all endometriosis stages were analyzed together although this may be clinically distinct entities. Wider implications of the findings Endometriosis patients have the same risk to have P4<10.6ng/mL the day before FET as non-endometriosis patients. Vaginal progesterone, with subcutaneous supplementation if necessary, appears user-friendly, leading to a comparable live birth rate to that of patients with normal progesterone levels before transfer, regardless of endometriosis status. Trial registration number not applicable

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

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

Contribution of Matrix Metalloproteinase-7 Genotypes to Endometriosis Risk in Taiwan.

The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort. In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology. The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021). MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese.

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis.

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease.

Clinical characteristics and treatment outcomes of patients with a septate uterus complicated by endometriosis

ObjectivesPatients with a septate uterus often have endometriosis, which can exacerbate their adverse pregnancy outcomes. We aimed to describe the clinical characteristics and treatment outcomes of patients with a septate uterus complicated by endometriosis. Study designThis retrospective study included patients who had a septate uterus complicated by endometriosis and were treated in Wuhan Tongji Hospital in the past 10 years. The characteristics of patients with a septate uterus and endometriosis were collected and described in terms of their preoperative and postoperative pregnancy outcomes. ResultsThere were 24 cases with a complete septate uterus and 49 cases with an incomplete septate uterus.Combinations of other malformations are more common in patients with complete septate uterus. In patients with a septate uterus, endometriosis often affected the ovaries, most commonly the left side (P < 0.001). Non-significant difference in the staging of endometriosis between complete and incomplete septate uterus (P= 0.812). Surgical treatment greatly improved the reproductive function and increased the live birth rate of patients with a septate uterus complicated by endometriosis (P < 0.001). ConclusionsCompared to a septate uterus uncomplicated endometriosis, a septate uterus complicated by endometriosis significantly affects reproductive function. Surgical treatment can significantly improve the pregnancy outcomes of patients with a septate uterus and endometriosis. Clinicians should pay attention to timely diagnosing and treating these patients.

Pregnancy-related complications in patients with endometriosis in different stages

BackgroundEndometriosis is one of the most common and costly diseases among women. This study was carried out to investigate pregnancy outcomes in women with endometriosis because of the high prevalence of endometriosis in reproductive ages and its effect on pregnancy-related complications outcomes.MethodsThis was a cross-sectional study performed on 379 pregnant women with endometriosis who were referred to the endometriosis clinic of the Avicenna Infertility Treatment Center from 2014 to 2020. Maternal and neonatal outcomes were assessed for the endometriosis group and healthy mothers. The group with endometriosis was further divided into two groups: those who underwent surgery and those who either received medication alone or were left untreated before becoming pregnant. The analysis of the data was done using SPSS 18.ResultsThe mean age of the patients was 33.65 ± 7.9 years. The frequency of endometriosis stage (P = 0.622) and surgery (P = 0.400) in different age groups were not statistically significant. The highest rates of RIF and infertility were in stages 3 (N = 46, 17.2%) (P = 0.067), and 4 (N = 129, 48.3%) (P = 0.073), respectively, but these differences were not statistically different, and the highest rate of pregnancy with ART/spontaneous pregnancy was observed in stage 4 without significant differences (P = 0.259). Besides, the frequency of clinical/ectopic pregnancy and cesarean section was not statistically different across stages (P > 0.05). There is no significant relationship between endometriosis surgery and infertility (P = 0.089) and RIF (P = 0.232). Most of the people who had endometriosis surgery with assisted reproductive methods got pregnant, and this relationship was statistically significant (P = 0.002) in which 77.1% (N = 138) of ART and 63% (N = 264) of spontaneous pregnancies were reported in patients with endometriosis surgery. The rate of live births (59.4%) was not statistically significant for different endometriosis stages (P = 0.638). There was no stillbirth or neonatal death in this study. All cases with preeclampsia (N = 5) were reported in stage 4. 66.7% (N = 8) of the preterm labor was in stage 4 and 33.3% (N = 4) was in stage 3 (P = 0.005). Antepartum bleeding, antepartum hospital admission, preterm labor, gestational diabetes, gestational hypertension, abortion, placental complications and NICU admission were higher in stage 4, but this difference had no statistical difference.ConclusionEndometriosis is significantly correlated with infertility. The highest rates of RIF and infertility are observed in stages 3 and 4 of endometriosis. The rate of pregnancy with ART/spontaneous pregnancy, preterm labor, preeclampsia and pregnancy-related complications is higher in stage 4. Most of the people who had endometriosis surgery with assisted reproductive methods got significantly pregnant. Clinical/ectopic pregnancy, cesarean sections, and live birth were not affected by the endometriosis stages.

Heme metabolism and HO-1 in the pathogenesis and potential intervention of endometriosis.

Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase-1 (HO-1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions. Regulation occurs at molecular, cellular, and pathological levels. Numerous studies suggest that heme is an indispensable component in EM and may contribute to its pathogenesis. The regulatory role of heme in EM encompasses cytokines, signaling pathways, and kinases that mediate cellular responses to external stimuli. HO-1, a catalytic enzyme in the catabolic phase of heme, mitigates heme's cytotoxicity in EM due to its antioxidant, anti-inflammatory, and anti-proliferative properties. Certain compounds may intervene in EM by targeting heme metabolism, guiding the development of appropriate treatments for all stages of endometriosis.

Analysis of factors affecting pregnancy rate after laparoscopic surgery for infertility associated with endometriosis

ObjectiveTo analyze the factors that might influence the pregnancy rate in patients with infertility related to endometriosis (EMs) after undergoing laparoscopic surgery, providing guidance for our clinical diagnostic and therapeutic decision-making. MethodsA retrospective analysis was conducted on clinical records and 1-year postoperative pregnancy outcomes of 335 patients diagnosed with endometriosis-related infertility via laparoscopic surgery, admitted to our department from January 2018 to December 2020. ResultsThe overall pregnancy rate for patients with endometriosis (EMs) related infertility 1-year post-surgery was 57.3 %, with the highest pregnancy rate observed between 3 to 6 months after surgery. Factors such as Body Mass Index (BMI) (P = 0.515), presence of dysmenorrhea (P = 0.515), previous pelvic surgery (P = 0.247), type of EMs pathology (P = 0.893), and preoperative result of serum carbohydrate antigen 125 (CA125)（P = 0.615）had no statistically significant effect on postoperative pregnancy rates. The duration of infertility (P = 0.029), coexistence of adenomyosis (P = 0.042), surgery duration (P = 0.015), intraoperative blood loss (P = 0.050), preoperative result of serum anti-Müllerian hormone (AMH) (P = 0.002) and age greater than 35 (P = 0.000) significantly impacted postoperative pregnancy rates. The post-surgery pregnancy rate in patients with mild (Stage I-II) EMs was notably higher than those with moderate to severe (Stage III-IV) EMs (P = 0.009). Age (P = 0.002), EMs stage (P = 0.018), intraoperative blood loss (P = 0.010) and adenomyosis (P = 0.022) were the factors that affected the postoperative live birth rate. ConclusionFor patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors.

Soluble Factors CD14, CD163, and Migration Inhibitory Factor Are Associated with Endometriosis-Related Infertility

Objectives: Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serve as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. Design: Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. Participants: Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. Methods: The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. Results: Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the rASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the rASRM endometriosis score. In receiver operating characteristic analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. Limitations: Some limitations of the current study deserve to be underlined. First, the sensitive ELISA method was the sole-validated tool for detecting the markers in patient samples. Second, healthy or fertile women were not involved as the control group. Conclusions: The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.

Neutrophil to lymphocytes ratio in deep infiltrating endometriosis as a new toll for clinical management.

Several mechanisms, including altered local and systemic immune system, apoptosis, and new angiogenesis, are responsible for the development and progression of endometriosis. Over the years many markers have been studied, like CA 125 and, recently, neutrophil-to-lymphocyte ratio (NLR). This tool is cost-effectiveness and non-invasiveness as a marker of systemic inflammatory diseases. The aim of this study is to assess the role of NLR in the real-life management of patients with endometriosis in order to evaluate the possible association between this value and symptoms. We performed a retrospective analysis of 199 premenopausal women affected by endometriosis, from January 2013 to December 2020, evaluating the characteristics of disease, the symptoms and the NLR. Analyzing the neutrophiles, the mean ± SD value was 6.1 ± 4.5 × 103/ul, while for lymphocytes mean ± SD value was 1.8 ± 0.7.NLR was categorized according to its median value (> 2.62 vs ≤ 2.62). The comparison between NLR values and CA 125, endometriosis stage, dysmenorrhea and presence of chronic pelvic pain, adjusting for previous therapy did not find a significant association. An interesting result, although not significant, was the association between NLR and chronic pelvic pain (OR = 1.9). In the sub-group of patients without previous therapy this association is even stronger (OR = 4.8, 95% CI 0.5-50.2, p = 0.190). The link between NLR and chronic pelvic pain can provide a further hint to the clinician even when taking symptoms into account to develop a particular therapeutic treatment related to the various expressions of NLR. Finally, NLR may enable the creation of customized follow-up protocols that divide patients into high- and low-risk categories for endometriosis recurrence.

Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma.

The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.