Therapy For Endometriosis Research Articles

Adolescent Gynecological Surgeries: Cause for Concern

Introduction Gynecological surgery in adolescent girls (10–19 years) remains challenging due to remarkable differences in anatomy, physiology and need for fertility preserving conservative surgical approach. We aimed to identify the various gynecological causes, operative outcomes, and need for follow-up surgeries in adolescents. Methods A single-center hospital record-based retrospective study was conducted for gynecological surgeries performed on adolescents in a 5-year period with exclusion of obstetrical and nongynecological causes. Results Sixty-eight adolescents of mean age 16.77 ± 2.317 years underwent gynecological procedures wherein 63 (92.64%) were postmenarchal girls. Pain abdomen (75%), menstrual abnormality (47%), and abdominal swelling (47%) were their main complaints. Note that 35 (51.4%) surgeries performed were for adnexal masses and 24 (35.3%) for obstructive Mullerian anomalies or neovagina creation. Other indicated surgeries were uterine leiomyoma (4.4%), Bartholin’s cyst (5.8%), and pelvic abscess (1.4%). The mean interval of symptoms to the diagnosis was 1.22 ± 1.381 years while the mean diagnosis to surgery interval was 8.71 ± 5.880 days. A statistically significant difference (243.3 vs. 783.1 days, p < 0.00001) was found in the symptoms to diagnosis interval and the length of hospital stay (difference in means 16 days, p < 0.00001) in the two major operative groups. Minimal access surgery could be completed in 37% of cases. Complications encountered were bowel injury in 5.8%, bladder injury in 2.9%, blood transfusion requirement in 5.8%, and reoperation in 2.94%. Follow-up revealed one death, adjuvant chemotherapy in 7.3%, and suppressive hormone therapy for endometriosis in 13% of operated girls. Conclusion Diagnosis of a gynecological presentation is protracted and delayed in adolescents. Both diagnosis and surgery is challenging, and minimal invasive surgery is preferable. Malignancy diagnosis or exclusion, treatment, and follow-up should be prioritized to limit delays in the decision to treat. Timely and appropriate, as far as possible conservative surgery and adherence to follow-up protocols will ensure successful outcomes.

Sunitinib Reduced the Migration of Ectopic Endometrial Cells via p-VEGFR-PI3K-AKT-YBX1-Snail Signaling Pathway.

Endometriosis (EMs) is one of the most common gynecological diseases, lacking effective treatment. EMs are currently being treated with small molecule targeted therapy, which has resulted in a significant reduction in patient suffering. Our previous studies have shown that sunitinib plays an obvious role in migration. Consequently, the purpose of this study is to explore the molecular mechanism by which sunitinib suppressed the ectopic endometrial migration. The ectopic endometrial cells from patients were divided into two groups: the control group and the sunitinib group. Co-IP and protein spectrum assay were employed to filtrate differential proteins between two groups, and then, our study discovered a signaling pathway, p-VEGFR-PI3K-AKT-YBX1-Snail, in the cell of EMs. To confirm this signaling pathway, VEGF165 was added to the sunitinib group to upregulate the expression of VEGFR. Next, the expression of p-VEGFR, PI3K, AKT, YBX1, and snail was measured in the control group and sunitinib group (compared with the control group: p-VEGFR, PI3K, AKT, YBX1, and snail, ∗∗∗∗P < 0.0001) and the VEGFR+sunitinib group (compared with the sunitinib group: p-VEGFR, PI3K, AKT, and snail, ∗∗∗∗P < 0.0001; YBX1, ∗∗∗P < 0.001); finally, the outcome was as expected. In addition to in vitro experiments, we also conducted in vivo experiments in mice. In the EMs mouse model, we found sunitinib reduced the number of heterotopic foci (t = 11.16, ∗∗∗∗P < 0.0001) and inhibited the expression of p-VEGFR, YBX1, and snail by immunofluorescence. To sum up, sunitinib exactly reduced the migration of ectopic endometrial cells with the involvement of the p-VEGFR-PI3K-AKT-YBX1-Snail signaling pathway in both in vitro and in vivo experiments. This study suggests that sunitinib presents a potential targeted drug for EMs therapy.

O-155 What strategies help patients cope with endometriosis in everyday life: a doctor's perspective

Abstract Endometriosis is an enigmatic disease characterized by chronic pain and infertility and associated with a diminished quality of life. While surgery, pain medications and hormonal treatments are the mainstays of treating endometriosis, patients are increasing seeking complementary therapies to help them cope with their symptoms in everyday life. Too often, clinicians caring for women with endometriosis are at a loss when it comes to discussing or recommending such alternative therapies, as they are not part of typical western medical training. This lecture will review the evidence behind –or lack thereof—for many commonly sought therapies for endometriosis to enable physicians and clinicians to better counsel their patients. Topics to be addressed include: is there any benefit to special diets for endometriosis and endometriosis-associated pain? ; is there a role for physical activity or specific exercises in improving symptoms?; are yoga and meditation effective in helping women cope with endometriosis? ; are there specific phytotherapies that improve symptoms? ; has acupuncture been shown to help women cope with endometriosis symptoms? ; are there complementary therapies that improve fertility? In addition, based on clinical experience in treating with women with endometriosis, the importance of setting shared goals and expectations for treatment and supporting patients in their plans for attempting pregnancy and fulfilling the wish for a child will be discussed.

Estro-Progestins and Pain Relief in Endometriosis

Endometriosis is a benign, hormone-responsive chronic disease that affects women of reproductive age; long-term treatment to balance satisfactory tolerability with clinical efficacy is necessary for these patients. The first-line therapy for endometriosis is predominantly medical treatment, in order to improve symptoms or prevent post-surgical disease recurrence. Multiple factors including age and women preference, pain severity, and endometriosis stage must be considered in the choice of the most suitable therapy. Estrogen-progestogins are generally used as first-line hormone therapies among different medical options currently effective for endometriosis management. Several studies have shown that they are able to improve pain symptoms in most patients, are well tolerated, and are inexpensive. Combined hormonal contraception treatment, administered cyclically or continuously, with different types of hormones and route of administration, results in clinically noticeable decrease in dysmenorrhea, noncyclic pelvic pain, dyspareunia, and recurrence rate after surgery, and also in quality of life improvement.

Transvaginal Low Intensity Shockwave Therapy in Endometriosis (T-LISTE): Protocol for a Randomised pilot trial

ABSTRACT Background Endometriosis is a common disorder in women of childbearing age. Standard medical and surgical treatments are not always satisfactory. Shockwave therapy has been suggested as a possible novel treatment. There are no clinical data however to support this approach. This article describes the research protocol for a pilot interventional trial aiming to evaluate transvaginal low intensity shockwave therapy in women with endometriosis. Methods Adult women (anticipated N = 64) suffering from endometriosis will be recruited in a general gynaecology clinic and randomly allocated in a 1:1 ratio to an intervention group and a control group (parallel group design). The intervention group will receive 4 weekly sessions of transvaginal low intensity radial shockwave therapy. The control group will receive 4 sham procedures. The group allocation will be blinded to the patients but not to caregivers or data analysts (single blinded). Assessment will be carried at 1, 3 and 6 months. The primary endpoint is the visual analogue score for pelvic pain (dysmenorrhea, chronic pelvic pain, dysuria, dyschezia) and the deep dyspareunia score. Conclusion This prospective monocentric single blinded randomised controlled pilot trial will assess transvaginal low intensity shockwave therapy as a novel treatment for endometriosis. KEYWORDS: Endometriosis; Pelvic pain; Dysmenorrhea; Dyspareunia; Shockwave Therapy.

Utilization of immortalized B cells to identify SDCBP as a novel therapeutic target in ovarian carcinoma.

e14507 Background: We hypothesized that tumor-infiltrating B cells in endometriosis and endometriosis-associated ovarian cancer can be used to identify novel, targetable antigen domains to inhibit the progression of ovarian carcinomas. We aimed to identify targets that are spontaneously recognized by B-cell-derived antibodies within ovarian clear cell carcinoma (CCC), endometrioid carcinoma (EC), and endometriosis and to determine the preclinical anti-cancer efficacy of a candidate antibody that recognizes the extracellular domain of an identified target. Methods: B cells from freshly dissociated CCC (n = 2), EC (n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening in a proteome array. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. Tumor-promoting syndecan binding protein (SDCBP) was identified and SDCBP-reactive B cells were FACS-sorted and subjected to single cell B cell receptor sequencing to determine the variable heavy and light chain sequences of enriched clonotypes. We then generated a recombinant IgG4 antibody targeting SDCBP with the dominant VH/VL matching sequences. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer cell lines and tumor samples. In vivo studies compared anti-tumor potential of the α-SDCBP IgG4 with controls using immunodeficient mouse models of human CCC and high-grade serous ovarian carcinoma (HGSOC). Results: Nine accessible proteins were detected by both IgA and IgG in all samples, including SDCBP. SDCBP is expressed in ovarian cancer cell lines and tumor samples of multiple histologies, including CCC, EC, and HGSOC. Administration of α-SDCBP IgG4 in TOV21G (CCC) tumor-bearing mice significantly decreased tumor volume compared to non-antigen-specific irrelevant IgG4 (iIgG4, p = 0.002) and vehicle (0.001), and correspondingly trended toward decreased tumor weight compared to vehicle (p = 0.06). Likewise, administration of α-SDCBP IgG4 in OVCAR3 (HGSOC) tumor-bearing mice significantly decreased tumor volume compared to iIgG4 (p = 0.03) and trended toward decreased tumor weight (p = 0.06). Conclusions: An α-SDCBP IgG4 has demonstrated anti-tumor efficacy in SDCBP+ CCC and HGSOC, and SDCBP-targeted therapy for endometriosis and associated malignant conditions, as well as HGSOC, warrants further investigation.

The Promises of Natural Killer Cell Therapy in Endometriosis.

Endometriosis is a gynaecological disease defined by the growth of endometrium-like tissue outside the uterus. The disease is present in approximately 5–10% of women of reproductive age and causes pelvic pain and infertility. The pathophysiology is not completely understood, but retrograde menstruation and deficiency in natural killer (NK) cells that clear endometriotic cells in the peritoneal cavity play an important role. Nowadays, hormonal therapy and surgery to remove endometriosis lesions are used as treatment. However, these therapies do not work for all patients, and hormonal therapy prevents patients from getting pregnant. Therefore, new treatment strategies should be developed. Since the cytotoxicity of NK cells is decreased in endometriosis, we performed a literature search into the possibility of NK cell therapy. Available treatment options include the inhibition of receptor–ligand interaction for KIR2DL1, NKG2A, LILRB1/2, and PD-1/PD-L1; inhibition of TGF-β; stimulation of NK cells with IL-2; and mycobacterial treatment with BCG. In preclinical work, these therapies show promising results but unfortunately have side effects, which have not specifically been studied in endometriosis patients. Before NK cell treatment can be used in the clinic, more research is needed.

Transient modification of macrophages for activation their pro‐inflammatory functions

Macrophages are innate immune cells that play an important role in both physiological and pathological conditions. According to the concept of binary polarization, there are two the most polar states of macrophages: pro‐inflammatory and anti‐inflammatory macrophages. We proposed that targeted programming of macrophages derived from the specific monocyte subpopulation is perspective strategy for activation their inflammation properties that could be used in therapy of cancer or endometriosis. This work is devoted to the study of the effect of Indoleamine 2,3‐dioxygenase 1 (IDO1) and its inhibitor BIN1 on the shift in the polarization of macrophages into a pro‐inflammatory phenotype. We used magnetic sorting, differentiation, and further pro‐inflammatory polarization of CD14+ monocytes from the blood of healthy donors. We obtained data on the transcriptome and proteome and carried out a bioinformatic analysis to identify the most significant differences between two groups of cells – naive and pro‐inflammatory macrophages. IDO1 has been identified as an enzyme with immunomodulatory functions and is also involved in the catabolism of the essential amino acid L‐tryptophan. This enzyme is expressed in macrophages and its expression is induced by pro‐inflammatory cytokines. It was shown that the BIN1 protein is an inhibitor of IDO1 and can inhibit the growth of cancer cells. It was shown that upon the polarization of macrophages towards the pro‐inflammatory phenotype by LPS addition, the expression of IDO1 increases, while the expression of BIN1 decreases (p &lt;0.05). To reveal the influence of the IDO1 and BIN1 genes on the shift of the polarization of macrophages towards the M1 phenotype, we decided to carry out knockdown by using siRNAs on the primary line of CD14+‐derived macrophages. The efficiency of transfection was assessed at different concentrations of siRNA ranged from 30 to 80%, but high concentrations of siRNA led to non‐specific activation of pro‐inflammatory phenotype. Expression analysis confirmed the silencing of the genes IDO1 and BIN1 using 5 nM siRNA. It was shown that knockdown of IDO1 and BIN1 leads to increased expression of pro‐inflammatory genes (CCR7 and TNFa) and decreased the level of anti‐inflammatory interleukin 10. Also, co‐cultivation CD14+ macrophages after knockdown of genes IDO1 and BIN1 didn’t influent on macrophage’s phagocytic functions. The proposed study has a scientific novelty since for the first time a transient modification of the primary line of macrophages from blood CD14 + was carried out and the influence of IDO1 and BIN1 on the activation of the pro‐ or anti‐inflammatory phenotype was shown. Directed programming of macrophages is a new and rapidly developing field.

Polarized Macrophages As Potential Anti‐Endometrioid agent

Endometriosis is an estrogen‐dependent chronic inflammatory disease characterized by the presence of endometrial stroma and glands outside the endometrium. The gold standard in the treatment of endometriosis is laparoscopy but after that, the relapse rate is about 50%. Thus, the search for new effective non‐invasive methods of endometriosis therapy is an actual problem. Endometriosis has many properties similar to tumors including the fact that macrophages with an anti‐inflammatory phenotype (M2) prevail in the foci of endometriosis. It is already known that activated macrophages with a pro‐inflammatory phenotype (M1) have an antitumor effect. In this regard, we hypothesized that increasing the proportion of M1 macrophages could help in the treatment of endometriosis. The objectives of our work were (1) to assess the expression profile of macrophages in the foci of endometriosis in mice model of endometriosis; (2) to test the efficacy of administration of reprogrammed M1 macrophages as a possible anti‐endometrioid agent in the mouse.We studied the phenotypic profile of macrophages in the foci of endometriosis and the anti‐endometrioid activity of M1 macrophages on in vivoallogeneic model of mouse endometriosis induced in ovariectomized mice after intraperitoneal transplantation of the mouse uterus accompanied by 17β‐estradiol therapy. Analysis of the phenotypic profile of macrophages in the foci of endometriosis was carried out using immunohistochemical staining, western blot analysis, and qPCR. We obtained a reproducible model with lesions that had characteristic morphology. It was shown that macrophages with an anti‐inflammatory arginase1+ phenotype prevail in the foci of endometriosis compared with the intact endometrium. After verifying endometriosis development in mice, the experimental group was injected with M1‐polarized macrophages, while the control group was injected with unpolarized macrophages, and then the animals were monitored for two weeks. Macrophage cell line RAW264 was incubated with lipopolysaccharide (100 ng/ml) for 24 h to obtain M1‐polarized macrophages. M1‐polarization was verified by significant up‐regulation of MARCO, iNOS markers using western blot and qPCR analysis. After treatment of animals with M1 macrophages, we found that the number of foci and their sizes significantly decreased (p&lt;0.05) in comparison with control animals.In our work, we proved the predominance of anti‐inflammatory macrophages in the foci of endometriosis and obtained the first results of a positive effect of M1 macrophages on the regression of foci of endometriosis.

Deep immunophenotyping reveals endometriosis is marked by dysregulation of the mononuclear phagocytic system in endometrium and peripheral blood

BackgroundEndometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single-cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages.MethodsA case-control study was designed. Endometrial biopsies and blood (n = 60 total) were obtained from women with (n = 20, n = 17, respectively) and without (n = 14, n = 9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed: one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed.ResultsThe broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91+ macrophages overexpressed SIRPα (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease.ConclusionsA greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.

Endometriosis-Associated Angiogenesis and Anti-angiogenic Therapy for Endometriosis.

Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.

Water-Extracted Prunella vulgaris Alleviates Endometriosis by Reducing Aerobic Glycolysis.

Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. Prunella vulgaris is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of P. vulgaris is well-established. Therefore, in this work, we evaluated water-extracted P. vulgaris (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an in vitro study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.

Identification of NFASC and CHL1 as Two Novel Hub Genes in Endometriosis Using Integrated Bioinformatic Analysis and Experimental Verification.

BackgroundEndometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis.MethodsThree endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes.ResultsAmong the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions.ConclusionThis study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.

Recombinant interleukine-2 in the treatment of gynecological diseases

Recombinant interleukin-2, a structural analogue of human interleukin-2, used in the complex therapy of chronic endometritis, endometriosis, and preconception preparation increases the effectiveness of the treatment of gynecological diseases and reduces the risk of reproductive losses.

Endometrioid disease is a modern view of the problem

The article provides a review of specialized literature in order to generalize and systematize data on modern ideas about endometrioid disease in the clinical practice of doctors of various specialties. The social signifi cance of this disease is indicated. The article refl ects the main modern ideas about etiology and pathogenesis of endometriosis. Although there are a number of issues, they are not studied completely. The crucial role of the immune system malfunction in the formation of endometrioid disease is highlighted. The genetic ideas about the development of endometriosis are refl ected. Modern approaches to the treatment of endometriosis and the place of cholecalciferol in modern complex therapy of endometriosis are presented.

Cognitive Behavioral Therapy in Endometriosis, Psychological Based Intervention: A Systematic Review.

Endometriosis is an inflammatory disease that affects women of reproductive age, causing pain and the possibility of infertility. Endometriosis was associated to low life quality and research shows the impact of endometriosis in several areas of life, justifying how these patients are more likely to develop depression, anxiety, and stress. The aim of the present systematic review was to explore the field of psychology in endometriosis, identifying studies that used the cognitive behavioral therapy technique as a treatment for endometriosis and chronic pelvic pain. The keywords used were Endometriosis and Behavioral Therapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy; Mental Health; Psychological Techniques; Psychology; Psychotherapy; Mental Health Services; and the search was performed in the following databases: PubMed/Medline, Scielo, Lilacs, and Capes. The study followed the PRISMA guidelines and all studies whose intervention strategy used was related to cognitive-behavioral therapy were considered. Of the 129 articles found, only 5 were selected, and it was possible to identify that the psychological intervention whose approach brought cognitive-behavioral therapy techniques promoted a decrease in the sensation of pain, improvements in the scores of depression and stress, and significant changes in aspects of quality of life such as vitality, physical and social functioning, emotional well-being, control, and autonomy. Cognitive-behavioral therapy can be very promising to take care of the emotional side of those who have endometriosis However, the present systematic review highlights the need to develop more structured studies with consistent, clear and replicable methods to reach a psychological intervention protocol for patients who live with this gynecological-physical-emotional condition.

Surgical techniques for excision of juvenile cystic adenomyoma

The objectives of this video are to review causes of pelvic pain among adolescents and to discuss surgical techniques for safe and effective resection of juvenile cystic adenomyomas. We present a 16-year-old patient with chronic pelvic pain and ultrasound evidence of a 2.4cm adenomyoma. The lesion was specifically thought to represent a juvenile cystic adenomyoma (JCA), defined as a cystic lesion >1cm occurring in women under 30 years with severe dysmenorrhea that is distinct from the uterine cavity and surrounded by hypertrophic myometrium. Given minimal relief from medical therapy and high suspicion for co-existent endometriosis, our patient elected to undergo laparoscopic resection of adenomyoma and excision of pelvic lesions. Preoperative considerations discussed in this video include imaging to identify the location of the lesion and adjacent structures such as the uterine vessels, discontinuation of GnRH agonist for adequate intraoperative visualization, and the high likelihood of encountering endometriosis af the time of surgery. We review the following surgical techniques: 1) maximize visualization with use of a uterine manipulator and temporary oophoropexy, 2) optimize hemostasis via temporary uterine artery ligation and control of collateral blood vessels, 3) complete ureterolysis, 4) meticulous enucleation of adenomyoma, and 5) excision of co-existent endometriotic lesions. Surgical findings demonstrated a 2cm lesion along the left lower uterine segment and red-brown lesions along bilateral ovarian fossa, pathologically confirmed as adenomyoma and superficial endometriosis, respectively. This video presents strategies for safe and effective adenomyoma resection and treatment of refractory chronic pelvic pain in an adolescent.

Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis.

Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16–0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58–2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: −1.11 to −0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.

A Randomized Control Trial of Combined Surgical and Hormonal Therapy of Endometriosis

Aim: To evaluate the three therapy strategies including surgical therapy, hormonal therapy, and combined treatment for the management of endometriosis Study design: A multicentric randomized control trial Place and Duration: This study was conducted in 6 different hospitals of Pakistan, Muhammad Medical and Dental College Ratanabad Mirpurkhas, Social Security Landhi Hospital Karachi, Sindh Government CDF Hospital , Bilawal Medical College for Boys Jamshoro, Ghulam Muhammad Mahar Medical College Sukkur, Bahria International Hospital Karachi, Sandeman Provincial Hospital Quetta Pakistan Pakistan from June 2020 to June 2021. Methodology: The study included 360 participants with genital endometriosis. The age of the patients ranged from 18 years to 45 years. All the patients did not have any previous surgical intervention. The patients were randomly treated with one of the three treatments. A laparoscopic evaluation was done after three months of hormonal and combined therapy. Re-evaluation of surgically treated patients was done after 5 to 6 months. Stage of endometriosis, recurrence of symptoms, and the rate of pregnancy were noted in the re-evaluation phase of the study. Results: The overall cure rate of all types of endometriosis was 56.11% after every regimen of treatment. The cure rate after treatment from combined therapy was 60%. Those treated exclusively by hormone therapy showed a cure rate of 54.17%. A total of 54.17% of patients were cured exclusively by surgical treatment. The rate of recurrence was lowest in the patients given combined therapy. Dyspareunia and dysmenorrhea were significantly reduced. The overall rate of pregnancy was 53% to 64%. The rate of pregnancy was not different among all the groups. Conclusion: After giving hormonal therapy, surgical treatment, and combined treatment, it has been noticed that recurrence was lowest in the combined medical and surgical treatment group. The rate of pregnancy had also got better after all the means of treatment. The highest rate of cure was achieved by combined therapy. Keywords: Endometriosis, laparoscopy, hormone therapy, combined treatment, infertility, recurrence

Vitamin D inhibited endometriosis development in mice model through interleukin-17 modulation.

Endometriosis is a common, benign, estrogen-dependent, and chronic gynecological disease. Immune system disturbance and inflammatory abnormalities were involved in the pathogenesis of endometriosis. Therefore, it is logical to use vitamin D, which has an immunomodulatory capacity, as supportive therapy for endometriosis. This research aimed to study the effect of different doses of vitamin D on Interleukin-17 (IL-17) expression in endometriosis mice models. Endometriosis was induced in 24 mice divided into 4 groups of 6. Group C received no treatment, while groups T1, T2, and T3 received graded doses of oral vitamin D, sequentially 8, 16, and 24 IU, for 3 weeks. IL-17 expression and the extent of endometriotic peritoneal lesions were then measured and analyzed. Statistical tests were performed to see the difference in the mean area of endometriosis lesions and IL-17 expression between the control and treatment groups, as well as the correlation between the extent of endometriosis lesions and IL-17. Endometriosis lesions decreased after 16 and 24 IU of vitamin D administration (p 0.023 and 0.009). Endometriosis lesion also tends to be smaller after 8 IU of vitamin D supplementation, although insignificant (p > 0.05). IL-17 expression was significantly lower after 24 IU vitamin D administration compared to the untreated group (p = 0.004). Lower IL-17 expressions were also observed after 8 and 16 IU vitamin D administration, although insignificant (p = 0.452 and p = 0.645). IL-17 expression was moderately and positively correlated with the extent of endometriosis lesions (p = 0.012, rho = 0.505). By modulating the expression of IL-17 in endometriotic lesions, vitamin D inhibited the development of endometriotic lesions in the endometriosis mice model. The recommended vitamin D dose in this study was 24 IU.