Treatment Of Endometriosis Research Articles

Эффективность методов лечения бесплодия у пациенток с эндометриозом I–II стадии

Aim. To evaluate the effectiveness of surgical treatment and assisted reproductive technologies (ART) for infertility associated with stage I–II endometriosis, according to the revised American Society for Reproductive Medicine (rASRM) classification. Design. Randomized study. Materials and methods. This study included 62 women aged 25 to 41 years with infertility and stage I–II endometriosis, determined by clinical symptoms and magnetic resonance imaging data. Patients were randomized into 2 groups: group 1 (laparoscopy) — surgical treatment of endometriosis, followed by planning a spontaneous conception within 12 months (n = 35); group 2 (ART) — treatment of infertility associated with endometriosis using ART methods (n = 27). Reproductive outcomes in group 1 were assessed after 1 year from the date of surgical treatment; in group 2 — based on the results of 3 attempts of embryo transfer as part of the use of ART methods. Results. Rate of pregnancy (group 1 — 34.3%; group 2 — 33.3%; p = 0.937), pregnancy termination (group 1 — 25%; group 2 — 44.4%; p = 0.397), childbirth (group 1 — 20%; group 2 — 14.8%; p = 0.643) did not differ significantly between treatment groups. Conclusion. Surgical treatment and the use of ART methods in the treatment of infertility in patients with stage I–II endometriosis are equally effective. The choice of method may depend on the patient’s preference, medical history, characteristics and disease stage, the presence of concomitant pathology, as well as the other factors of infertility. Keywords: endometriosis, magnetic resonance imaging, surgical treatment of endometriosis, laparoscopy, infertility, assisted reproductive technologies, in vitro fertilisation, hormonal treatment.

Progesterone resistance in endometriosis: A pathophysiological perspective and potential treatment alternatives

AbstractBackgroundEndometriosis is a common gynecological disease affecting women of reproductive age. Patients with endometriosis frequently experience severe chronic pain and have higher chances to experience infertility. Progesterone resistance is a major problem that develops during the medical treatment of endometriosis, which often leads to treatment failure of hormonal therapies. Previous studies indicated that the dysregulation of progesterone receptors (PR) is the primary factor leading to progesterone resistance in endometriosis.MethodsThis review article systematically reviewed and summarized findings extracted from previously published papers available on PubMed, encompassing both experimental studies and clinical trials.Main findingsVarious determinants influencing PR expression in endometriosis have been identified, including the environmental toxins, microRNAs, cell signaling pathways, genetic mutations, and the pro‐inflammatory cytokines. The selective estrogen/progesterone receptor modulators have emerged as novel therapeutic approaches for treating endometriosis, offering potential improvements in overcoming progesterone resistance.ConclusionConcerns and limitations persist despite the newly developed drugs. Therefore, studies on unraveling new therapeutic targets based on the molecular mechanisms of progesterone resistance is warranted for the development potential alternatives to overcome hormonal treatment failure in endometriosis.

Seleno-relaxin analogues: effect of internal and external diselenide bonds on the foldability and a fibrosis-related factor of endometriotic stromal cells.

Human relaxin-2 (H2 relaxin) is a peptide hormone of about 6 kDa, first identified as a reproductive hormone involved in vasoregulation during pregnancy. It has recently attracted strong interest because of its diverse functions, including anti-inflammatory, anti-fibrotic, and vasodilatory, and has been suggested as a potential peptide-based drug candidate for a variety of diseases. Mature H2 relaxin is constituted by the A- and B-chains stabilized by two interchain disulfide (SS) bridges and one intrachain SS linkage. In this study, seleno-relaxins, SeRlx-α and SeRlx-β, which are [C11UA,C11UB] and [C10UA,C15UA] variants of H2 relaxin, respectively, were synthesized via a one-pot oxidative chain assembly (folding) from the component A- and B-chains. The substitution of SS bonds in a protein with their analogue, diselenide (SeSe) bonds, has been shown to alter the physical, chemical, and physiological properties of the protein. The surface SeSe bond (U11A-U11B) enhanced the yield of chain assembly while the internal SeSe bond (U10A-U15A) improved the reaction rate of the folding, indicating that these bridges play a major role in controlling the thermodynamics and kinetics, respectively, of the folding mechanism. Furthermore, SeRlx-α and SeRlx-β effectively reduced the expression of a tissue fibrosis-related factor in human endometriotic stromal cells. Thus, the findings of this study indicate that the S-to-Se substitution strategy not only enhances the foldability of relaxin, but also provides new guidance for the development of novel relaxin formulations for endometriosis treatment.

Adenosine Deaminase Family Acting on RNA 1 (ADAR1) May Be a De Novo Target for Endometriosis Treatment.

Adenosine deaminase family acting on RNA 1 (ADAR1) expression was examined to determine its correlation with endometriosis. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in a human endometriotic cell line. ADAR1 was examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR), and the apoptotic expression of ADAR1 small interfering RNA (siRNA) was confirmed using flow cytometry. The biological functions and inhibitory effects of ADAR1 knockdown were investigated using RT-PCR in a 12Z immortalized human endometriotic cell line. ADAR1 expression was significantly higher in patients with endometriosis than in those without (p<0.001). ADAR1 siRNA increased early and late apoptosis, compared to the mock (24.83%) and control (19.96%) cells. ADAR1 knockdown led to apoptosis through MDA5, RIG-I, IRF3, IRF7, caspase 3, caspase 7, and caspase 8 expression in the cell lines. ADAR1 is a potential novel therapeutic target in endometriosis.

Endometriosis Patients Have an Increased Risk of Experiencing Long-Covid Symptoms: Results from a Cross-Sectional Multicenter Study.

Women are more at risk for developing long-term symptoms after a COVID-19 infection. Only limited data are available for patients with coexisting endometriosis and/or menstrual pain symptoms. A total of 840 premenopausal women with menstrual pain and/or endometriosis were included in this observational cross-sectional study using an online survey platform. A total of 840 women with menstrual pain (mean age 30.7 ± 6.9, 15-54 years) were studied. Of these, 714 (84.2%) had a COVID-19 infection, 123 did not (14.5%). A total of 312 subjects had acute COVID-19 (AC) with symptoms ≤4 weeks (43.7%), 132 (18.5%) developed postacute COVID-19 syndrome (PC), and 88 (12.3%) had "long Covid" (LC). There were no statistical differences regarding number of vaccination shots between the three groups AC, PC, and LC. A total of 582 patients with surgically confirmed endometriosis (SCE) showed a twofold increased risk of LC [odds ratio (OR): 2.12, 2.18-3.84] in comparison with AC subjects. In SCE the comorbidity anxiety disorder (OR: 2.08, 1.14-3.81) and depression (OR: 2.02, 1.15-3.56) further increased the risk of LC. LC subjects had a significantly higher disturbance level of menstrual pain (p = 0.002), were more restricted in job (p < 0.001), leisure (p = 0.002), and family activities (p < 0.001), and had a higher number of endometriosis surgeries (p = 0.003). Subjects with SCE had a twofold increased risk of LC (in comparison to subjects with nonconfirmed endometriosis menstrual pain). In patients with SCE concomitant diagnosis of depression or anxiety disorder further twice-fold increased risk of LC. Further studies are needed if it is possible to reduce LC risk by improving the treatment of those secondary diagnoses and whether the type of endometriosis treatment can reduce LC occurrence (holistic, coanalgetic, hormonal).

Prevalence, Surgical, and Medical Management of Patients with Endometriosis amongst Indian Women

Objective: This study aims to determine the prevalence of endometriosis in women in South India, the epidemiological factors involved, and evaluate the symptomatic burden associated with it. Design: A large-scale Hospital-based study was conducted among women of reproductive age (16 to 44 years) in the state of Telangana between March 2018 and March 2023. A randomized multi-stage stratified sampling method was adopted and included 2,400 women who were screened using a validated structured questionnaire. Patients presenting with symptoms indicative of endometriosis underwent additional assessment using abdominal ultrasonography (AUS) and serum cancer antigen 125 (CA125) tests. For confirmation, laparoscopy was offered to the patients who consented. Patients who declined laparoscopy were given the option of undergoing magnetic resonance imaging (MRI) instead. Results: Among 2,400 women who participated, 60 women have been diagnosed with endometriosis during the 5-year study period. The prevalence of endometriosis was found to be 2.5%. The mean age of participants was 15.2 ± 3.5 years and the mean age at menarche was found to be 12.9 ± 1.1 years. Out of 60 participants diagnosed with endometriosis 30% (n = 18) experienced irregular menstrual cycles. Approximately 33.3% (n = 20) of the women reported experiencing Dysmenorrhea, with 28.4% (n = 17) complaining of dyspareunia. Among the cases with menstrual pain, exhibited ultrasound findings suggestive of endometriosis, with elevated CA125 levels observed in 45% (n = 27) of these cases. All 60 patients who consented to laparoscopic confirmation, exhibited positive histo-pathological evidence of endometriosis. The prevalence of endometriosis is found to be significant in women of reproductive age group and found to be associated with high rates of infertility in 15 (25%) patients. The results of this study showed that the prevalence of endometriosis is found to be 2.5% which is similar to the other studies reported. The severity of endometriosis during laparoscopy was assessed using the rAFS staging system, revealing rates of 55% and 45% for disease in Stages I &amp; II, Stages III, &amp; IV, respectively. Conclusion: Our study concludes that endometriosis predominantly affects women in the reproductive age group and is often associated with primary infertility. The laparoscopic findings are identified as a standard tool for both diagnosis and treatment of endometriosis.

Resolution of the First Ukrainian endometriosis forum “Drug treatment for endometriosis-associated pelvic pain. The quality of a woman’s life”

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis.The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

Anti-inflammatory, antioxidant, antiangiogenic, and therapeutic efficacy of neroli oil in rats with endometriotic lesions.

Endometriosis is a serious health problem among women of reproductive age, with pelvic pain and infertility. Given the limited success of current treatments, this study explores Neroli oil (N.O.) effects on inflammation, oxidation, angiogenesis, and tissue remodeling implicated in endometriosis. Albino Wistar female rats were used to simulate an endometriosis model. Groups were established for comparison: a control, an endometriosis model, a N.O.-treated group, and a N.O.-treated group postendometriosis induction. The study focused on Tumor necrosis factor-alpha (TNF-α), Interleukin 6, Interleukin 8, vascular endothelial growth factor (VEGF), myeloperoxidase, Matrix metalloproteinase-1 (MMP-1), nitric oxide, superoxide dismutase, catalase, and anti-mullerian hormone values, as well as histopathological evaluations of endometriotic foci. AMH values showed a significant increase in the endometriosis group treated with N.O. compared with the endometriosis group (p < 0,01).A statistically significant decrease was found in MMP-1 level in the endometriosis group that underwent N.O. (p < 0.001). Increased CAT (p < 0.0001) and decrease in nitric oxide (p < 0.01) are found in N.O.-treated endometriosis group. TNF-α levels in the endometriosis group showed a statistically significant increase in the endometriosis group when compared with the control and sham group (p < 0.001, p < 0.01 respectively). In our study, a statistically significant increase was observed in VEGF levels (p < 0.001) in endometriosis group and significant decrease in the N.O. administered endometriosis model group. Groups treated with N.O. showed decreased inflammation and congestion scores. Histopathological assessments demonstrated reduced inflammation and tissue remodeling signs in endometriotic foci. This study highlights the potential of N.O. in the treatment of endometriosis, owing to its anti-inflammatory, antioxidant, and antiangiogenic properties that can disrupt chronic processes. Our findings lend support to utilization of herbal remedies for the management of endometriosis, thereby emphasizing the necessity for additional comprehensive investigations in the future.

Regulatory mechanism of GPER in the invasion and migration of ectopic endometrial stromal cells in endometriosis

ABSTRACT Endometriosis (EMS) is a chronic inflammatory disorder of high incidence that causes serious reproductive consequences. High estrogen production is a consistently observed endocrine feature of EMS. The present study aims to probe the molecular mechanism of G protein-coupled estrogen receptor 1 (GPER) in the invasion and migration of ectopic endometrial stromal cells (Ect-ESCs) and provides a new rationale for EMS treatment. Eutopic and ectopic endometrial tissues were collected from 41 EMS patients, and primary ESCs were separated. GPER, miR-16-5p, and miR-103a-3p levels in cells and tissues were determined by qRT-PCR or Western blot assay. Cell viability, proliferation, invasion, and migration were evaluated by CCK-8, colony formation, and Transwell assays. The upstream miRNAs of GPER were predicted by databases, and dual-luciferase assay was performed to validate the binding of miR-16-5p and miR-103a-3p to GPER 3’UTR. GPER was highly expressed in EMS tissues and Ect-ESCs. Inhibition of GPER mitigated the proliferation, invasion, and migration of Ect-ESCs. GPER was regulated by miR-16-5p and miR-103a-3p. Overexpression of miR-16-5p and miR-103a-3p negatively regulated GPER expression and inhibited the invasion and migration of Ect-ESC. In conclusion, GPER promoted the invasion and migration of Ect-ESCs, which can be reversed by upstream miR-16-5p and miR-103a-3p.

Potential Of Mahkota Dewa Fruit (Phaleria macrocarpa) Flavonoids Extract and Dienogest to Reduce IL-17A Levels in Mice Endometriosis Model

Endometriosis is an inflammatory disease that occurs in glands outside the endometrium. Interleukin 17 (IL-17) is a proinflammatory cytokine degrading Th17 cells, which play an essential role in several inflammatory diseases. IL-17 expression is upregulated in serum, peritoneal fluid (PF), and endometriotic lesions from patients with endometriosis. Usually, treatment for endometriosis is dienogest. However, it has many side effects if used long-term. Fruit and seeds of Phaleria macrocarpa have various critical biological activities in the form of extracts such as antimicrobial, anti-inflammatory, and antioxidant activities. This study aims to analyze the effect of comparing flavonoid fruit extract of Phaleria macrocarpa and dienogest on IL-17A levels in endometriosis mice. A total of 35 endometriosis model mice were divided into seven groups, namely the group of healthy mice (without any treatment), the endometriosis group, and the endometriosis group, which were given the treatment of flavonoid fruit extracts of Phaleria macrocarpa and dienogest. The sample used in this study was peritoneal fluid. The enzyme-linked immunosorbent assay (ELISA) measured IL-17A levels in each observation group. The hypothesis was tested using One-Way ANOVA analysis with SPSS software version 26. This study found a significant difference (p&lt;0.05) between the mean values of the positive control group and the negative control group. There was also a significant difference (p&lt;0.05) in the mean value IL-17 between the treatment groups that were given sphalerite macrocarpa and dienogest extracts. Flavonoid fruit extract of Phaleria macrocarpa had a significant effect on reducing IL-17A levels in endometriosis model mice, and there is a significant difference with dienogest. Thus, the flavonoid fruit extract of Phaleria macrocarpa can potentially treat endometriosis by decreasing inflammatory factors.

Atorvastatin exerts dual effects of lesion regression and ovarian protection in the prevention and treatment of endometriosis

Endometriosis is a frequent, chronic, estrogen-dependent and inflammatory gynecological disease leading to pain and infertility. Clinical and metabolic studies reveal that patients with endometriosis are susceptible to hyperlipemia and lipid dysfunction, putting them at ascending risk of cardiovascular diseases. Statins constitute a group of cholesterol-lowering drugs with pleiotropic effects. A plethora of researches have proved their ability to inhibit the growth of ectopic lesions in endometriosis. However, concerns exist about their possible adverse effects on ovarian function. This study aimed to investigate the possible effect of atorvastatin on the ovarian endocrine function and fertility capacity in the prevention and treatment of endometriosis. Here, 5 mg/kg atorvastatin was intraperitoneally injected to the endometriosis mice once a day for consecutive fourteen days during and after the development of endometriotic implants. The results indicated that atorvastatin not only led to regression of the ectopic lesions, but also caused no discernible harm to the ovary for both the preventive and the therapeutic models. In addition, it elicited a protective effect on the ovarian reserve and fertility possibly by reducing inflammation in the ovary. Hence, atorvastatin could be a promising drug for endometriosis prevention and treatment.

Ovarian Stimulation for In Vitro Fertilization and Reproductive Outcome after Surgical Treatment of Endometriosis Compared with Tubal Factor Infertility.

Endometriosis is a common cause of infertility among reproductive-age women. A low ovarian reserve is associated with the presence of endometriotic cysts, and this is accentuated even more after surgery. Patients with a history of endometrioma are a special category of poor ovarian reserve requiring in vitro fertilization (IVF). The aim of this retrospective study was to evaluate the characteristics and outcome of ovarian stimulation and embryo transfer in women with a history of ovarian surgery for endometrioma compared with a control group with tubal factor infertility. A total of 146 patients had previous laparoscopic cystectomy for endometrioma (group A) and their IVF results were compared with 136 patients with documented tubal obstruction (group B). In both groups, the most frequently used ovarian stimulation protocol was the short antagonist in 84.24% versus 80.88%. The number of stimulation days was between 6 and 15 days in the two groups with a mean value of 12.76 days in group A and 9.47 days in group B. The clinical pregnancy rate was 26.77% in the endometrioma group and 39.68% in the tubal obstruction group. Patients with a history of endometrioma are less likely to conceive than those with tubal obstruction despite having similar ovarian reserve and stimulation results.

TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis in the process of endometriosis

BackgroundT cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) initially discovered on the surface of Th1 cells, negatively regulates immune responses and mediates apoptosis of Th1 cells. An increasing number of studies have since shown that TIM-3 is crucial in the genesis and development of immune diseases, cancers, and chronic infectious illnesses. However, the effect of TIM-3 on endometriosis is still unknown.MethodsQuantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry were used to measure TIM-3 levels in endometriosis. Cell Counting Kit-8, 5-ethynyl-2’-deoxyuridine, colony-forming, Transwell® migration, Matrigel® invasion, and flow cytometry assays were used to explore the function of TIM-3 in vitro, and xenograft experiments in nude mice were used to assess its role in vivo. According to the RNA seq, brain-derived neurotrophic factor (BDNF) was screened. The involvement of specific proliferation-related signaling molecules was determined by transfecting a plasmid and adding an inhibitor in vivo and in vitro.ResultsTIM-3 mRNA and protein expression levels were significantly higher in eutopic and ectopic endometrial tissues than in normal endometrial tissues. By examining the effects of TIM-3 overexpression and knockdown on cell proliferation, migration, and invasion in vitro, and lesions formation in vivo, we found that the expression of TIM-3 was positively correlated with cell proliferation and clone formation in vitro, as well as lesions growth in nude mice. By adding the phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT) pathway inhibitor LY294002 and knocking down PI3K, we further verified that TIM-3 promotes proliferation in vivo and in vitro via the PI3K pathway. By transfecting the plasmid into ESC cells and gave inhibitors to endometriotic rats models, we tested that TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis.ConclusionTIM-3 can promote the proliferation of endometriosis by BDNF-mediated PI3K/AKT axis in vivo and in vitro, which may provide a new therapeutic target for the treatment of endometriosis.

Polycondensed Peptide-Based Polymers for Targeted Delivery of Anti-Angiogenic siRNA to Treat Endometriosis.

Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing endometriotic lesions, some patients require multiple surgeries. Therefore, finding non-surgical treatments for EM is of great interest. One of the promising approaches is anti-angiogenic therapy using siRNA-therapeutics to target the expression of the VEGFA gene. Peptide-based polymers have shown promise as siRNA delivery systems due to their biocompatibility and ease of modification. We conducted a study to evaluate the effectiveness of the R6p-cRGD peptide carrier as a non-viral vehicle for delivering siRNA to endothelial cells in vitro and endometrial implants in vivo. We investigated the physicochemical properties of the siRNA-complexes, assessed cellular toxicity, and examined the efficiency of GFP and VEGFA genes silencing. Furthermore, we tested the anti-angiogenic effects of these complexes in cellular and animal models. The transfection with siRNA complexes led to a significant increase in VEGFA gene knockdown efficiency and a decrease in the migration of endothelial cells. For the animal model, we induced endometriosis in rats by transplanting endometrial tissue subcutaneously. We evaluated the efficiency of anti-angiogenic therapy for EM in vivo using anti-VEGF siRNA/R6p-RGD complexes. During this assessment, we measured the volume of the implants, analyzed VEGFA gene expression, and conducted CD34 immunohistochemical staining. The results showed a significant decrease in the growth of endometriotic implants and in VEGFA gene expression. Overall, our findings demonstrate the potential of the R6p-cRGD peptide carrier as a delivery system for anti-angiogenic therapy of EM.

The effect of hormone-modulating therapy during pregravid preparation on the course of pregnancy and childbirth in patients with a history of endometriosis

BACKGROUND: Endometriosis is a benign proliferation of tissue similar in morphological and functional characteristics with endometrium outside the uterine. In the structure of gynecological diseases, it ranks on the third place and its prevalence is growing steadily every year.&#x0D; AIM: The aim of this study was to analyze the features of pregnancy and childbirth in patients with endometriosis who received hormone-modulating therapy during pregravid preparation.&#x0D; MATERIALS AND METHODS: This retrospective analysis of the course of pregnancy and childbirth in patients with a surgically confirmed diagnosis of varying severity endometriosis (n = 140) in history was carried out at the Center for Diagnosis and Treatment of Endometriosis, The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia. The control group consisted of pregnant women without endometriosis (n = 50).&#x0D; RESULTS: Before pregnancy, 82.1% (n = 115) of patients with endometriosis used hormone-modulating therapy, while 17.9% (n = 15) of patients did not comply with the given therapy. During therapy, 70% (n = 98) of patients mentioned decreasing in the severity of pain. In patients with a history of endometriosis, threatened miscarriage took the leading place and was identified in 24.3% of cases in the first and second trimesters and in 33.6% of cases in the third trimester of pregnancy, which was consistently higher than in the control group. Miscarriage was observed in 38.5% of patients and recurrent pregnancy loss in 18.6% of women. Preeclampsia was diagnosed in 23.8% (n = 33) of patients with endometriosis. The use of hormone-modulating therapy during pregravid preparation was shown to reduce the risk of developing preeclampsia among patients with endometriosis by 4.1 times, and the use of dienogest 2 mg as the therapy of endometriosis to reduce the frequency of preeclampsia by ten times in comparison with patients who did not receive any treatment. Fetal growth restriction was observed in 18.6% (n = 26) of patients with endometriosis. The presence of endometriosis increased the likelihood of developing fetal growth restriction by 3.6 times and reduced the likelihood of having a large fetus by 2.7 times. Preterm birth was observed in 20% (n = 28) of patients with endometriosis, which is four times higher than in the control group (p = 0.019). Most pregnant women with a history of endometriosis – 64.3 % (n = 90) of patients – were delivered by cesarean section, while 35.7% (n = 50) of women had vaginal birth, which was 3.34 times higher than the frequency of cesarean section in the control group.&#x0D; CONCLUSIONS: Patients with a history of endometriosis are at high risk for the development of obstetric complications associated with the pathogenesis of the disease. An integrated approach to the treatment of endometriosis with the use of hormone-modulating therapy during pregravid preparation and personalized management of patients in different trimesters of pregnancy can reduce the risk of complications of pregnancy and childbirth.

Identification of central genes for endometriosis through integration of single-cell RNA sequencing and bulk RNA sequencing analysis.

This study aimed to identify the key genes involved in the development of endometriosis and construct an accurate predictive model to provide new directions for the diagnosis and treatment of endometriosis. Using bioinformatics analysis, we employed the single-cell cell communication method to identify the key cell subtypes. By combining chip data and integrating differential analysis, WGCNA analysis, and the least absolute shrinkage and selection operator (LASSO) model, key genes were identified for immune infiltration and functional enrichment analyses. Cell communication analysis identified tissue stem cells as the key subtype. Differential analysis revealed 1879 differentially expressed genes, whereas WGCNA identified 357 module genes. The LASSO model further selects 4 key genes: Adipocyte Enhancer Binding Protein 1(AEBP1), MBNL1, GREM1, and DES. All 4 key genes showed significant correlations with immune cell content. Moreover, these genes were significantly expressed in single cells. The predictive model demonstrated good diagnostic performance. Through scRNA-seq, WGCNA, and LASSO methodologies, DES, GREM1, MBNL1, and AEBP1 emerged as crucial core genes linked to tissue stem cell markers in endometriosis. These genes have promising applications as diagnostic markers and therapeutic targets for endometriosis.

The Role of Herbal Medicine as An Alternative Treatment Option for Endometriosis: A Literature Review

Introduction: Endometriosis is a benign gynecological disorder characterized by ectopic growth of endometrial tissue. This condition may deteriorate patient’s quality of life due to pain as its main manifestation and its complications, including impaired fertility and risk of ovarian cancer. Current standard endometriosis treatment still yields numerous side effects and controversy. Thus, herbal medicine is hoped to be the safer alternative treatment with excellent efficacy for endometriosis. Methods: The search of literature published in English or Bahasa Indonesia was performed by incorporating the search queries “endometriosis”, “herbal therapy”, “silymarin”, “curcumin”, “Viburnum opulus”, “Pueraria”, “Allium sativum”, “black garlic”, “naringenin” on databases including PubMed, Cochrane, Springer, Science Direct, Nature, and Google Scholar. The studies included were in vitro studies, in vivo studies, and clinical trials. Results: Various herbal treatments have been widely studied regarding their anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, cardioprotective, antiallergy, and immunomodulatory capacity. A lot of herbal compounds have the potential to suppress and manage endometriosis through various mechanisms, such as inhibiting the migration and adhesion of endometriosis to other tissues, suppressing inflammatory response in endometriosis pathogenesis, generating antioxidant, inhibiting estrogen activity, and inducing apoptosis of endometriosis cell through a number of signaling pathways. Conclusion: Herbal medicine has the potential to manage endometriosis through various mechanisms. Further research is needed regarding the efficacy of herbal therapy in managing endometriosis.

Indian Medicinal Plants for the Management of Endometriosis: A Comprehensive Review on their phytopharmacology

Endometriosis is a chronic gynecological disorder characterized by the aberrant growth of endometrial tissue outside the uterus, resulting in severe pain and infertility. Conventional treatments often come with limitations and side effects, prompting a quest for alternative therapies. Medicinal plants, integral to traditional medicine systems, have emerged as potential solutions. This review delves into the phytopharmacology and chemistry of medicinal plants employed in endometriosis treatment. An exhaustive search revealed pertinent studies concerning medicinal plant use in endometriosis treatment. These studies were scrutinized for their phytopharmacological attributes and active chemical constituents. Numerous medicinal plants exhibited anti-inflammatory, analgesic, antioxidant, immunomodulatory, and hormone-regulating properties, pivotal in endometriosis management. Mechanisms encompassed the suppression of inflammatory mediators, modulation of estrogen signaling, mitigation of oxidative stress, and enhancement of immune function. Furthermore, key chemical constituents responsible for these effects were pinpointed and classified into classes such as flavonoids, terpenoids, alkaloids, and phenolic compounds. These bioactive agents elicited their actions via diverse molecular targets, including cyclooxygenase enzymes, estrogen receptors, nuclear factor-kappa B, and reactive oxygen species. The findings underscore the potential of medicinal plants as adjunct therapies for endometriosis. Nonetheless, additional preclinical and clinical investigations are imperative to substantiate their efficacy, safety, and optimal dosing. Grasping the phytopharmacology and chemistry of medicinal plants in endometriosis treatment lays the groundwork for novel therapeutic agent development, spotlighting the capacity of natural products to combat this intricate gynecological ailment.

Machine learning algorithms for a novel cuproptosis-related gene signature of diagnostic and immune infiltration in endometriosis

Endometriosis (EMT) is an aggressive disease of the reproductive system, also called “benign cancer”. However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.

Visual Analogue Scale Cut-off Point of Seven Represents Poor Quality of Life in Patients with Endometriosis.

Establishing objective criteria to assess endometriosis symptoms is crucial in defining therapeutic strategies. The visual analogue scale (VAS) is the most used system to enhance the accuracy and reduce the subjectivity of pain assessment, and symptoms of endometriosis are considered severe when the VAS score is ≥ 7cm. Pain symptoms can significantly impact patients' quality of life, resulting in psychological and social distress. The aim of this study is to evaluate whether a VAS cut-off point of 7cm for each pain symptom correlates with a diminished quality of life in women with endometriosis. This retrospective study included 1129 patients who underwent surgical treatment for endometriosis. Dysmenorrhea, acyclic pelvic pain, deep dyspareunia, dyschezia, and dysuria were assessed using a 0-10cm VAS. The Short Form-36 (SF-36) questionnaire was employed to evaluate the quality of life 6months prior to surgery. Dysmenorrhea was the most prevalent symptom reported in 93.6% of cases, with a mean VAS of 7.6cm. The quality of life reported was reduced in most patients, with domain scores ranging from 49.4 to 80.1. The mean SF-36 scores in all domains were significantly lower in patients with severe pain (VAS score ≥ 7cm) compared to those with mild to moderate pain (VAS < 7cm). This trend was observed across all evaluated pain symptoms. Our research demonstrates that the prevalent VAS cut-off point for establishing severe pain symptoms in endometriosis (VAS ≥ 7cm) accurately represents the negative impact of the disease on women's quality of life, as assessed via the SF-36 questionnaire.