Pathophysiology and Clinical Implications of Ovarian Endometriomas.

Ovarian endometriomas affect many patients with endometriosis and have significant effects on quality of life, fertility, and risk of malignancy. Endometriomas range from small (1-3 cm), densely fibrotic cysts to large (20 cm or greater) cysts with varying degrees of fibrosis. Endometriomas are hypothesized to form from endometriotic invasion or metaplasia of functional cysts or alternatively from ovarian surface endometriosis that bleeds into the ovarian cortex. Different mechanisms of endometrioma formation may help explain the phenotypic variability observed among endometriomas. Laparoscopic surgery is the preferred first-line modality of diagnosis and treatment of endometriomas. Ovarian cystectomy is preferred over cyst ablation or sclerotherapy for enabling pathologic diagnosis, improving symptoms, preventing recurrence, and optimizing fertility outcomes. Cystectomy for small, densely adherent endometriomas is made challenging by dense fibrosis of the cyst capsule obliterating the plane with normal ovarian cortex, whereas cystectomy for large endometriomas can carry unique challenges as a result of adhesions between the cyst and pelvic structures. Preoperative and postoperative hormonal suppression can improve operative outcomes and decrease the risk of endometrioma recurrence. Whether the optimal management, fertility consequences, and malignant potential of endometriomas vary on the basis of size and phenotype remains to be fully explored.

An update on endometriosis biomarkers.

Endometriosis is a debilitating gynecologic disorder characterized by chronic pelvic pain, pelvic adhesions and infertility. The gold standard diagnostic modality is histologically by tissue biopsy, although it can be diagnosed empirically if symptoms improve with medical treatment. A delayed diagnosis of endometriosis often leads to a significant impairment in quality of life and work productivity; hence, significant morbidity has been shown to bear a detrimental impact on society and the economy. The ongoing novel investigation into biomarkers for diagnostic or prognostic evaluation of endometriosis may aid in earlier detection, and thereby, improve patient quality-of-life as well as minimize morbidity. Currently, no single biomarker has been validated for endometriosis; however, there are emerging data on the utility of microRNA for diagnosis and prognosis of disease activity. In this brief review, we will identify and categorize the novel biomarkers for endometriosis.

The Prevalence of Endometriosis in Patients with Unexplained Infertility.

Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments. While biopsy remains the gold standard for diagnosis, emerging noninvasive screening methods are gaining prominence. These tests can indicate endometriosis in cases of unexplained infertility, offering valuable insights to patients and physicians managing both obstetric and non-obstetric conditions. In a retrospective cross-sectional study involving 215 patients aged 25 to 45 with unexplained infertility, diagnostic laparoscopy was performed after unsuccessful reproductive technology attempts. Pathology results revealed tissue abnormalities in 98.6% of patients, with 90.7% showing endometriosis, confirmed by the presence of endometrial-like glands and stroma. The study underscores the potential role of endometriosis in unexplained infertility cases. Although the study acknowledges selection bias, a higher than previously reported prevalence suggests evaluating endometriosis in patients who have not responded to previous reproductive interventions may be justified. Early detection holds significance due to associations with ovarian cancer, prolonged fertility drug use, pregnancy complications, and elevated post-delivery stroke risk.

Use of the Free Endometriosis Risk Advisor App as a Non-Invasive Screening Test for Endometriosis in Patients with Chronic Pelvic Pain and/or Unexplained Infertility.

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA's non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being.

TNFα-Induced Altered miRNA Expression Links to NF-κB Signaling Pathway in Endometriosis.

Endometriosis is a common gynecological inflammatory disorder characterized by immune system dysregulation, which is involved in lesion initiation and progression. Studies have demonstrated that several cytokines are associated with the evolution of endometriosis, including tumor necrosis factor-α (TNFα). TNFα is a non-glycosylated cytokine protein with potent inflammatory, cytotoxic, and angiogenic potential. In the current study, we examined the ability of TNFα to induce dysregulation of microRNAs (miRNAs) linked to NFkB signaling pathways, thus contributing to the pathogenesis of endometriosis. Using RT-qPCR, the expression of several miRNAs was quantified in primary cells derived from eutopic endometrium of endometriosis subjects (EESC) and normal endometrial stromal cells (NESC), and also TNFα-treated NESCs. The phosphorylation of the pro-inflammatory molecule NF-κB and the candidates of the survival pathways PI3K, AKT, and ERK was measured by western blot analysis. The elevated secretion of TNFα in EESCs downregulates the expression level of several miRNAs significantly in EESCs compared to NESCs. Also, treatment of NESCs with exogenous TNFα significantly reduced the expression of miRNAs in a dose-dependent manner to levels similar to EESCs. In addition, TNFα significantly increased the phosphorylation of the PI3K, AKT, ERK, and NF-κB signaling pathways. Notably, treatment with curcumin (CUR, diferuloylmethane), an anti-inflammatory polyphenol, significantly increased the expression of dysregulated miRNAs in EESC in a dose-dependent manner. Our findings demonstrate that TNFα is upregulated in EESCs, which subsequently dysregulates the expression of miRNAs, contributing to the pathophysiology of endometriotic cells. CUR effectively inhibits the expression of TNFα, subsequently altering miRNA levels and suppressing the phosphorylation of AKT, ERK, and NF-κB.

TNFα-induced altered miRNA expression links to NF-κB signaling pathway in endometriosis.

Endometriosis is a common gynecological inflammatory disorder characterized by immune system dysregulation, which is involved in lesion initiation and progression. Studies have demonstrated that several cytokines are associated with the evolution of endometriosis, including tumor necrosis factor-α (TNFα). TNFα is a non-glycosylated cytokine protein with potent inflammatory, cytotoxic, and angiogenic potential. In the current study, we examined the ability of TNFα to induce dysregulation of microRNAs (miRNAs) linked to NFkB-signaling pathways, thus contributing to the pathogenesis of endometriosis. Using RT-QPCR, the expression of several miRNAs were quantified in primary cells derived from eutopic endometrium of endometriosis subjects (EESC) and normal endometrial stromal cells (NESC) and also TNFα treated NESCs. The phosphorylation of the pro-inflammatory molecule NF-κB and the candidates of the survival pathways PI3K, AKT and ERK was measured by westernblot analysis. The elevated secretion of TNFα in EESCs downregulates the expression level of several miRNAs significantly (p < 0.05) in EESCs compared to NESC. Also treatment of NESCs with exogenous TNFα significantly reduced the expression of miRNAs in a dose-dependent manner to levels similar to EESCs. In addition, TNFα significantly increased the phosphorylation of the PI3K, AKT, ERK, and NF-κB signaling pathways. Notably, treatment with curcumin (CUR, diferuloylmethane), an anti-inflammatory polyphenol, significantly increased the expression of dysregulated miRNAs in EESC in a dose-dependent manner. Our findings demonstrate that TNFα is upregulated in EESCs, which subsequently dysregulates the expression of miRNAs, contributing to the pathophysiology of endometriotic cells. CUR effectively inhibits the expression of TNFα, subsequently altering miRNA levels and suppresses the phosphorylation of AKT, ERK, and NF-κB.

Revisiting microsurgical principles for the minimally invasive surgeon.

OBJECTIVE: To demonstrate basic microsurgical techniques and revisit the importance of following microsurgical principles in minimally invasive surgery. DESIGN: Video demonstration of various surgical cases portraying proper microsurgical techniques as well as the consequences of deviating from these principles. SETTING: Tertiary referral practice. PATIENT(S): Reproductive-aged women with a desire to preserve reproductive organs and fertility potential. INTERVENTION(S): We present surgical cases demonstrating the management of tubal and paratubal pathologies in which extra care must be taken to avoid inadvertent injuries of normal anatomic structures. We also portray the proper management of ovarian dermoid cysts and endometriomas to maximize the preservation of ovarian reserve and minimize complications. We have stressed the importance of ensuring safe tissue containment and extraction to avoid complications such as port site metastasis along with parasitic and iatrogenic myomas. MAIN OUTCOME MEASURE(S): Implementation of microsurgical techniques including delicate tissue handling, judicious use of energy sources, and proper tissue containment and extraction. RESULT(S): Nonadherence to microsurgical principles can result in detrimental surgical outcomes, including adhesions, parasitic myomas, port site metastasis, peritonitis, and compromised ovarian reserve. CONCLUSION(S): Microsurgical principles are of paramount importance to improve patient outcomes in reproductive surgeries. These tenets should be uniformly applied in all surgical procedures. As surgeons who perform minimally invasive surgeries, we must revisit these principles and advocate for their training and universal implementation.

Adnexal masses during pregnancy: diagnosis, treatment, and prognosis.

Adnexal masses are identified in pregnant patients at a rate of 2 to 20 in 1000, approximately 2 to 20 times more frequently than in the age-matched general population. The most common types of adnexal masses in pregnancy requiring surgical management are dermoid cysts (32%), endometriomas (15%), functional cysts (12%), serous cystadenomas (11%), and mucinous cystadenomas (8%). Approximately 2% of adnexal masses in pregnancy are malignant. Although most adnexal masses in pregnancy can be safely observed and approximately 70% spontaneously resolve, a minority of cases warrant surgical intervention because of symptoms, risk of torsion, or suspicion of malignancy. Ultrasound is the mainstay of evaluation of adnexal masses in pregnancy because of accuracy, safety, and availability. Several ultrasound mass scoring systems, including the Sassone, Lerner, International Ovarian Tumor Analysis Simple Rules, and International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adneXa scoring systems have been validated specifically in pregnant populations. Decisions regarding expectant vs surgical management of adnexal masses in pregnancy must balance the risks of torsion or malignancy with the likelihood of spontaneous resolution and the risks of surgery. Laparoscopic surgery is preferred over open surgery when possible because of consistently demonstrated shorter hospital length of stay and less postoperative pain and some data demonstrating shorter operative time, lower blood loss, and lower risks of fetal loss, preterm birth, and low birthweight. The best practices for laparoscopic surgery during pregnancy include left lateral decubitus positioning after the first trimester of pregnancy, port placement with respect to uterine size and pathology location, insufflation pressure of less than 12 to 15 mm Hg, intraoperative maternal capnography, pre- and postoperative fetal heart rate and contraction monitoring, and appropriate mechanical and chemical thromboprophylaxes. Although planning surgery for the second trimester of pregnancy generally affords time for mass resolution while optimizing visualization with regards to uterine size and pathology location, necessary surgery should not be delayed because of gestational age. When performed at a facility with appropriate obstetrical, anesthetic, and neonatal support, adnexal surgery in pregnancy generally results in excellent outcomes for pregnant patients and fetuses.

Hystero-embryoscopy: evaluation and evacuation of spontaneous missed abortions.

OBJECTIVE: To demonstrate the steps for hystero-embryoscopic evaluation of a 7-week spontaneous missed abortion and evacuation of the products of conception. Illustrate the surgical technique and highlight its advantages in improving the evaluation of spontaneous missed abortions. DESIGN: Video case presentation and demonstration of surgical technique. SETTING: Tertiary referral center. PATIENT(S): The patient provided consent for the video and its publication. INTERVENTION(S): Following vaginoscopy, the cervix was approached without prior blind cervical dilation. Navigation from the endocervix to the endometrial cavity was performed using a 2.9-mm diameter hysteroscope. The endometrial cavity was thoroughly inspected revealing an intact gestational sac and submucosal fibroids. An operative grasper was introduced, the chorion and amnion were penetrated, and embryoscopy was performed. In-flow was reduced for external morphological inspection of the embryo, which was then grasped and retrieved. The procedure was continued by introducing of a 26-french bipolar resectoscope, after which the products of conception were excised without electricity and sent for histologic and genetic analyses. MAIN OUTCOME MEASURE(S): This procedure allowed for proper embryonic evaluation and hysteroscopic evacuation of products of conception was successfully performed. RESULT(S): Cytogenic analysis of this case revealed a female embryo with trisomy 15. No maternal and fetal cell admixture was noted in the analysis, allowing a precise diagnosis. CONCLUSION(S): Hystero-embryoscopy is a valuable diagnostic and therapeutic procedure for cases of missed abortion. It may reveal embryonic morphological abnormalities, expand the diagnostic spectrum in the evaluation of pregnancy loss, and avoid potential complications from blind curettage.

Laparoscopically assisted hysteroscopic removal of an interstitial pregnancy.

OBJECTIVE: To illustrate a combined technique of hysteroscopy and laparoscopy for the management of interstitial ectopic pregnancies. DESIGN: A description of a patient case and demonstration of a surgical technique. SETTING: Tertiary referral center. PATIENT(S): A 33-year-old woman, gravida 2, para 0-0-1-0 status post in vitro fertilization cycle with single embryo transfer, was diagnosed with an unruptured right interstitial pregnancy at 5 weeks of gestation. She has a history of a pregnancy of unknown location with her first in vitro fertilization transfer and received methotrexate. The beta-human chorionic gonadotropin level was 2,726 mIU/mL. She was counseled on treatment options and declined treatment with methotrexate because of the negative side effects she experienced previously. She opted for surgical management and desired to keep her fallopian tubes if possible because she wished to try for spontaneous conception. INTERVENTION(S): The patient underwent multipuncture video laparoscopy, and a bulge was seen at the right cornua. Video hysteroscopy initially revealed an empty uterine cavity. Using atraumatic graspers, the interstitial pregnancy was gently pushed further into the uterine cavity using a milking technique. The pregnancy was then able to be visualized hysteroscopically. Products of conception were gently dislodged and removed with graspers, followed by a suction curettage. MAIN OUTCOME MEASURE(S): This technique resulted in minimal blood loss, preservation of reproductive organs, and expedient return to conception planning. RESULT(S): The postoperative course was uncomplicated, and the patient was discharged the same day as surgery. After the procedure, weekly beta-human chorionic gonadotropin was drawn until the level reached <1 mIU/mL, which occurred after 4 weeks. Hysterosalpingography was performed 2 months after the procedure and demonstrated bilateral tubal patency. CONCLUSION(S): In select patients, an early interstitial pregnancy can be safely removed using the described technique. Although hysteroscopic removal of interstitial pregnancies is not a new concept, the addition of simultaneous video laparoscopy provides the benefit of allowing for fertility-sparing removal of the pregnancy, even if it is not initially visualized hysteroscopically. The use of this technique may result in minimal blood loss and preservation of the fallopian tubes. Furthermore, with the myometrium integrity maintained, the patient may resume sooner attempts at conception.

Suburethral Endometriosis as Clinical Finding of Extensive Disease.

Objective: Endometriosis spreading to the vagina is rare, present in only 0.02% of women with symptomatic endometriosis. Suburethral lesion site is exceptional. In an extensive literature review only 4 cases of suburethral endometriosis were identified. Our objective is to present a case of primary vaginal suburethral endometriosis in a 31-year old patient who underwent laparoscopic evaluation and to perform a literature review on this topic. Methods and Procedures: Case report presentation based on information extracted from patient database. A review of literature with a Medline search using key words urethral endometriosis, suburethral endometriosis, or urethral diverticulum was undertaken. Results: This case report describes a case of a 31-year old female patient referred for severe pelvic pain, worsening during menstruation. On physical examination a 2 cm suburethral endometriotic lesion was found as the initial presentation. Her examination was also significant for enlarged, tender uterus and adnexa. Based on examination and imaging, adenomyosis and endometriosis were suspected. Surgical evaluation revealed extensive endometriosis with lymph node involvement at laparoscopic exploration. The review of literature revealed only 4 cases where suburethral endometriosis was previously identified. Conclusion: Primary vaginal suburethral endometriosis, although rare, could be an indication of extensive endometriosis. This case highlights the importance of careful clinical examination, surgical excision, and laparoscopic evaluation when identifying suburethral vaginal endometriotic lesions.

Hysteroscopy-assisted laparoscopic salpingectomy for interstitial pregnancy without cornual resection.

OBJECTIVE: To illustrate a novel surgical management technique for interstitial ectopic pregnancies (IP). DESIGN: Video description of the case, demonstration of the surgical technique, reevaluation at the 6-week postoperative follow-up, and review of the advantages of this surgical technique for IP. SETTING: Tertiary referral center. PATIENT(S): A 42-year-old gravida 2 para 1-0-0-1, underwent a successful in vitro fertilization (IVF) cycle with a single embryo transfer and had an early ultrasound diagnosis of IP with cardiac activity. After failed medical management with a single dose of methotrexate, she was referred to us for surgical management. Transvaginal ultrasound revealed fluid in the cul-de-sac and confirmed a right interstitial ectopic pregnancy with an estimated gestational age of 6 weeks. The myometrium at the periphery of the implantation site was 1-1.5 mm, and the "interstitial line sign" was seen. After counseling for possible treatment modalities, the patient opted for surgical management, planning for further IVF treatment. Her preoperative ß-human chorionic gonadotropin level (ß-hCG) was 3241 IU/L. Her surgical history was significant for a previous myomectomy via laparotomy and an elective lower transverse C-section. INTERVENTION(S): Hysteroscopy assisted by multipuncture video laparoscopy surgery was performed. Hysteroscopic resection was not feasible as the ectopic was not visualized as described previously. Using normal saline as the distension media and with the hysteroscope aimed at the right ostium, the hydrostatic pressure was increased transiently to dissect the ectopic pregnancy and facilitate the next surgical step. Laparoscopically, the ectopic pregnancy was milked with atraumatic graspers and mobilized from the cornua into the tube creating enough proximal length for salpingectomy. Right salpingectomy was achieved using high-frequency bipolar with no complications. MAIN OUTCOME MEASURE(S): Hysteroscopy-assisted laparoscopy technique allows for several advantages, including a short operative time and minimal blood loss. No sutures were required and the myometrial architecture was left undisrupted. RESULT(S): The postoperative course was uncomplicated, and the patient was discharged on the same day of surgery. The patient's ß-hCG level dropped from 3,241 to 139 IU/L after 48 hours. Two weeks later, the ß-hCG level was 3 IU/L. A follow-up ultrasound was performed six weeks postoperatively confirming the integrity of the myometrium without defects and proportional wall thickness on both sides. The patient was referred back to her infertility specialist to resume IVF treatment with no remarkable delay. CONCLUSION(S): In select cases and the presence of a proficient laparoscopic surgeon, early diagnosed IP can be removed safely using the described novel technique. While an interval conception of 3-6 months is recommended after conventional surgical procedures for IP, this technique can be comparable to salpingectomy.

Use of a shaving technique for surgical management of partial ureteral obstruction due to endometriosis.

OBJECTIVE: To illustrate the surgical management of advanced endometriosis causing extrinsic ureteral compression. DESIGN: Video description of the case, demonstration of the surgical technique, reevaluation at 14-year follow-up, and review of urogenital endometriosis. Patient provided consent for the video recording and publication. This surgical report with no identifying patient data was exempt from Institutional Review Board approval. SETTING: Tertiary referral center. PATIENT(S): A 42-year-old nulligravida with a known history of endometriosis presented with persistent pelvic pain and no other specific symptoms. She had previously undergone a diagnostic laparoscopy demonstrating advanced endometriosis involving multiple organs, including the urinary tract. She was referred to us for further surgical management. Preoperative intravenous pyelogram showed partial obstruction and constriction of a long portion of the midpelvic and distal left ureter with proximal hydroureter, consistent with extrinsic ureteral compression. INTERVENTION(S): The patient underwent operative video laparoscopy using a multipuncture technique, with enterolysis, extensive left ureterolysis, shaving of periureteral constrictive fibrosis and endometriosis, cystoscopy, and placement of left ureteral stent. MAIN OUTCOME MEASURE(S): There was extensive endometriosis and fibrotic adhesions involving the left pelvic sidewall. Proximal hydroureter was noted to the pelvic inlet secondary to severe periureteral fibrosis from the pelvic brim to the bladder meatus, with significant narrowing of the pelvic ureter. The endometriosis was resected using hydrodissection and shaving with a carbon dioxide laser. Histopathologic evaluation of the resection specimens confirmed endometriosis. RESULT(S): An intravenous pyelogram performed 4 weeks postoperatively revealed ureteral patency and resolving hydroureter, and her ureteral stent was removed. Annual renal ultrasounds for the subsequent 2 years were normal. Fourteen years later, she remained asymptomatic on no suppressive treatment. A follow-up intravenous pyelogram was performed and showed a normal urinary tract with bilateral ureteral patency and no recurrent strictures or hydroureter. CONCLUSION(S): In selected cases, conservative shaving of periureteral fibrotic endometriosis avoids ureteral resection and has acceptable outcomes.

Optimal Management of Endometriosis and Pain.

The pathophysiology of endometriosis-associated pain involves inflammatory and hormonal alterations and changes in brain signaling pathways. Although medical treatment can provide temporary relief, most patients can achieve long-term sustained pain relief when it is combined with surgical intervention. Owing to its complexity, there is an ongoing debate about how to optimally manage endometriosis-associated pain. We believe optimal management for this condition requires: 1) possible egg preservation in affected young patients with and without endometriomas; 2) preoperative medical suppression to inhibit ovulation and to avoid removal of functional cysts that might look like endometriomas; and 3) postoperative hormonal suppression to decrease recurrence, but this treatment should be modified according to disease severity, symptoms, and fertility goals.

Thoracic Endometriosis Syndrome: A Review of Diagnosis and Management.

BACKGROUND: Endometriosis is characterized by the presence of endometrial-like glands and stroma outside the uterine cavity and is believed to affect 6%-10% of reproductive-age women. Endometriosis within the lung parenchyma or on the diaphragm and pleural surfaces produces a range of clinical and radiological manifestations. This includes catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules, resulting in an entity known as thoracic endometriosis syndrome (TES). DATABASE: Computerized searches of MEDLINE and PubMed were conducted using the key words "thoracic endometriosis," "catamenial pneumothorax," "catamenial hemothorax," and "catamenial hemoptysis." References from identified sources were manually searched to allow for a thorough review. CONCLUSION: TES can produce incapacitating symptoms for some patients. Symptoms of TES are nonspecific, so a high degree of clinical suspicion is warranted. Medical management represents the first-line treatment approach. When this fails or is contraindicated, definitive surgical treatment for cases of suspected TES uses a combined video laparoscopy performed by a gynecologic surgeon and video-assisted thoracoscopic surgery performed by a thoracic surgeon. Postoperative hormonal suppression may further reduce disease recurrence.

Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-κB signaling pathway.

Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Due to altered sex steroid receptor concentrations and other signaling defects, eutopic endometriotic tissues have an attenuated response to progesterone. This progesterone-resistance contributes to lesion survival, proliferation, pain, and infertility. The current agency-approved hormonal therapies, including synthetic progestins, GnRH agonists, and danazol are often of limited efficacy and counterproductive to fertility and cause systemic side effects due to suppression of endogenous steroid hormone levels. In the current study, we examined the effects of curcumin (CUR, diferuloylmethane), which has long been used as an anti-inflammatory folk medicine in Asian countries for this condition. The basal levels of proinflammatory and proangiogenic chemokines and cytokines expression were higher in primary cultures of stromal cells derived from eutopic endometrium of endometriosis (EESC) subjects compared with normal endometrial stromal cells (NESC). The treatment of EESC and NESC with CUR significantly and dose-dependently reduced chemokine and cytokine secretion over the time course. Notably, CUR treatment significantly decreased phosphorylation of the IKKα/ß, NF-κB, STAT3, and JNK signaling pathways under these experimental conditions. Taken together, our findings suggest that CUR has therapeutic potential to abrogate aberrant activation of chemokines and cytokines, and IKKα/ß, NF-κB, STAT3, and JNK signaling pathways to reduce inflammation associated with endometriosis.