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.

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.

Discovering endometriosis biomarkers with multiplex cytokine arrays.

BACKGROUND: Chronic pelvic pain is often overlooked during primary examinations because of the numerous causes of such "vague" symptoms. However, this pain can often mask endometriosis, a smoldering disease that is not easily identified as a cause of the problem. As such, endometriosis has been shown to be a potentially long-term and often undiagnosed disease due to its vague symptoms and lack of any non-invasive testing technique. Only after more severe symptoms arise (severe pelvic pain, excessive vaginal bleeding, or infertility) is the disease finally uncovered by the attending physician. Due to the nature and complexity of endometriosis, high throughput approaches for investigating changes in protein levels may be useful for elucidating novel biomarkers of the disease and to provide clues to help understand its development and progression. METHODS: A large multiplex cytokine array which detects the expression levels of 260 proteins including cytokines, chemokines, growth factors, adhesion molecules, angiogenesis factors and other was used to probe biomarkers in plasma samples from endometriosis patients with the intent of detecting and/or understanding the cause of this disease. The protein levels were then analyzed using K-nearest neighbor and split-point score analysis. RESULTS: This technique identified a 14-marker cytokine profile with the area under the curve of 0.874 under a confidence interval of 0.81-0.94. Our training set further validated the panel for significance, specificity, and sensitivity to the disease samples. CONCLUSIONS: These findings show the utility and reliability of multiplex arrays in deciphering new biomarker panels for disease detection and may offer clues for understanding this mysterious disease.

Bowel endometriosis: diagnosis and management.

The most common location of extragenital endometriosis is the bowel. Medical treatment may not provide long-term improvement in patients who are symptomatic, and consequently most of these patients may require surgical intervention. Over the past century, surgeons have continued to debate the optimal surgical approach to treating bowel endometriosis, weighing the risks against the benefits. In this expert review we will describe how the recommended surgical approach depends largely on the location of disease, in addition to size and depth of the lesion. For lesions approximately 5-8 cm from the anal verge, we encourage conservative surgical management over resection to decrease the risk of short- and long-term complications.

Development and history of morcellators.

PURPOSE OF REVIEW: Controversy exists surrounding extraction of tissue in gynecologic surgery using morcellators following cases of disseminated uterine cancers discovered after the use of electromechanical morcellators. This chapter traces the history of tissue extraction in gynecology and reviews the evolving scientific data and opinions regarding the future of morcellation. RECENT FINDINGS: Since the initial Food and Drug Administration warning about morcellation in 2014, subsequent studies do not support the Food and Drug Administration's high incidence of occult uterine cancer. Current research continues, focusing on methods of contained tissue morcellation, both laparoscopically and vaginally. SUMMARY: Minimally invasive surgical techniques have revolutionized gynecology, drastically reducing the need for open procedures. To maximize patient safety while preserving the rapid recovery and low morbidity of laparoscopic and vaginal approaches, optimal methods of tissue extraction need to be developed and promulgated.

TEMPORARY REMOVAL: Celebrating the Past, Present and IDEAL Future AAGL.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Retinoic acid biosynthesis is impaired in human and murine endometriosis.

Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography in eutopic endometrial biopsies (EBs) and ELs from 42 patients with pathologically confirmed endometriosis. The ATRA levels were reduced, whereas the retinol and retinyl ester concentrations were elevated in EL compared with EB tissue. Similar results were found in a mouse model of endometriosis that used green fluorescent protein-positive endometrial tissue injected into the peritoneum of syngeneic hosts to mimic retrograde menses. The ATRA biosynthesis in vitro in retinol-treated primary human endometrial stromal cell (ESC) cultures derived from ELs was reduced compared with that of ESCs derived from patient-matched EBs. Correspondingly, RBP1 expression was reduced in tissue and ESCs derived from EL versus EB. Rbp1(-/-) mice showed reduced endometrial ATRA concentrations compared with wild type, associated with loss of tissue organization and hypercellularity. These findings provide the first quantitative measurements of ATRA in human endometrium and endometriosis, demonstrating reduced ATRA in ectopic tissue and corresponding ESC cultures. Quantitation of retinoids in murine endometriosis and in Rbp1(-/-) mice supports the contention that impaired ATRA synthesis caused by reduced RBP1 promotes an "endometriosis phenotype" that enables cells to implant and grow at ectopic sites.

Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis.

Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell-cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/ß-actin ratios=.4±1.5 in control and =1.2±0.3 in endometriosis biopsies (P<0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2±0.2- versus 1.7±0.4-fold, P<0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted.

Laparoscopically-assisted, hysteroscopic removal of an interstitial pregnancy with a fertility-preserving technique.

Described is a novel surgical management of an unruptured interstitial pregnancy with preservation of the ipsilateral fallopian tube and uterine cornua. The patient was a 34-year-old woman, gravida 3, para 1, with an unruptured left interstitial pregnancy at 9 weeks' gestation, who desired preservation of fertility. The ectopic pregnancy was entirely removed via laparoscopically assisted hysteroscopy with a fertility-preserving surgical technique, with minimal blood loss, preservation of reproductive organs, restoration of anatomy, a patent ipsilateral fallopian tube, and expedient return to normal reproductive function. After the procedure, serial human chorionic gonadotropin levels were obtained until they were <5 mIU/mL. A hysterosalpingogram obtained 2 months after the procedure showed normal uterine and fallopian tube contour and bilateral tubal patency. We conclude that this laparoscopically assisted hysteroscopic technique is a safe and efficient fertility-preserving approach to management of an unruptured interstitial pregnancy.

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.

A rare case of primary extranodal marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix in the setting of endometriosis.

Extranodal marginal zone B-cell lymphomas are uncommon. Most occur in the gastrointestinal tract. Marginal zone B-cell lymphomas of the female genital tract are rare, and few cases exist of marginal zone B-cell lymphomas of the uterus, cervix, and fallopian tubes. We report the first marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix arising in endometriosis.

AAGL Practice Report: Practice Guidelines for the Management of Hysteroscopic Distending Media: (Replaces Hysteroscopic Fluid Monitoring Guidelines. J Am Assoc Gynecol Laparosc. 2000;7:167-168.).

The objective of this guideline is to provide clinicians with evidence-based information about commonly used and available hysteroscopic distending media to guide them in their performance of both diagnostic and operative hysteroscopy. While necessary for the performance of hysteroscopy and hysteroscopically-directed procedures, distending media, if absorbed systemically in sufficient amounts, can have associated adverse events, including life-threatening complications. Consequently, understanding the physical properties and the potential risks associated with the use of the various distending media is critical for the safe performance of hysteroscopic procedures. This report was developed under the direction of the Practice Committee of the AAGL as a service to their members and other practicing clinicians.

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.

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.

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.

Outcomes of Laparoscopic Cesarean Scar Defect Repair: Retrospective and Observational Study.

Cesarean scar defect, also known as niche, isthmocele, uteroperitoneal fistula and uterine diverticulum, is a known complication after cesarean delivery. Due to the rising cesarean delivery rates, niche has become more common and can present as irregular bleeding, pelvic pain, infertility, cesarean scar pregnancy and uterine rupture. Treatments for symptomatic cesarean scar defect vary and include hormonal therapy, hysteroscopic resection, vaginal or laparoscopic repair, and hysterectomy. We report on the safety and efficacy of our method of repairing cesarean scar defects in 27 patients without adverse outcomes: two-layer repair where the suture does not enter the uterine cavity. Our method of laparoscopic niche repair improves symptoms in nearly 77% of patients, restores fertility in 73% of patients, and decreases the time to conception.

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.