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Objective: To demonstrate the effects of the selective G protein-coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs)., Design: Experimental in vitro study., Setting: University hospital., Patient(s): A total of 33 patients with ovarian endometrioma., Intervention(s): Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1., Main Outcome Measure(s): The primary outcomes were cell proliferation, measured using the WST-8 assay; cell cycle, as analyzed using flow cytometry, fluorescent immunocytochemistry, and cytotoxicity; caspase activity, as measured by fluorescent and luminescent enzyme assays; and protein expression levels, as determined by Western blot analysis., Result(s): G-1 suppressed ESC proliferation in a concentration-dependent manner. The inhibitory effect was not blocked when GPER signaling pathways, including the GPER itself, were inhibited. G-1 induced cell cycle arrest and accumulation in the sub-G1 phase in ESCs. Immunofluorescence analysis demonstrated that G-1 interrupted microtubule assembly at the mitotic phase. G-1 also induced caspase-3-dependent apoptosis without significant cytotoxicity., Conclusion(s): G-1 suppressed proliferation and induced apoptosis in ESCs, suggesting the potential use of this compound as a therapeutic drug for the treatment of endometriosis., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether decreased estrogen receptor alpha (ER-α) expression in endometriotic lesions could be balanced by an increased expression of estrogen receptor-related receptors (ERRs). To evaluate whether ERR-α expression is influenced by hormonal change in fertile and menopausal women., Design: Prospective controlled study., Setting: University Hospital, Department of Gynecology., Patient(s): Twenty-five women: 20 women of reproductive age with (n = 10) and without (control; n = 10) endometriosis and 5 menopausal women., Intervention(s): Real-time polymerase chain reaction (qPCR). Immunohistochemistry., Main Outcome Measure(s): The ER and ERR expression levels were studied by reverse transcriptase-qPCR, ELISA, and immunohistochemistry using endometriotic and normal endometrial tissues. The ERR-α protein distribution was performed by immunohistochemistry in fertile and menopausal women., Result(s): Increased levels of ER-β were associated with ER-α, ERR-α, and ERR-γ reductions in ectopic tissue but not in eutopic and normal endometria. Similar levels of ERR-β were found in women with and without endometriosis. The ERR-α expression was similar in proliferative and secretory endometrial samples, whereas a down-regulation of this receptor was found in atrophic tissue., Conclusion(s): Our data confirm the up-regulation of ER-β as the principal receptor involved in the progression of human endometriosis. In addition, we found that ERR-α seems to be unresponsive to hormonal changes during the menstrual cycle., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report a unique case of hyperreactio luteinalis in pregnancy associated with ovarian torsion and subsequent development of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome., Design: Case report., Setting: University medical center., Patient(s): A 34-year-old primigravida woman with ovarian torsion in 13 weeks of pregnancy and subsequent intrauterine growth restriction (IUGR) and HELLP syndrome., Intervention(s): Laparoscopic salpingo-oophorectomy due to the ovarian torsion and cesarean section (CS) due to the development of HELLP syndrome., Main Outcome Measure(s): HELLP syndrome., Result(s): In the first trimester the patient had symptoms of acute abdomen due to the ovarian torsion. Both ovaries were enlarged and multicystic. Hormonal studies confirmed an abnormally elevated level of hCG (192.000 IU/L), mild hyperthireosis, and hyperandrogenemia. Laparoscopic salpingo-oophorectomy was performed. At 30 weeks of pregnancy, IUGR was confirmed sonographically and clinically, and at 33 weeks severe preeclampsia developed. One week later, HELLP syndrome occurred. Emergency CS was preformed, and she delivered a female newborn weighing 1,640 g. Seven days after delivery, blood pressure and hormonal status returned to normal., Conclusion(s): Hyperreactio luteinalis due to the abnormally high level of hCG in the first trimester could be a consequence of inappropriate trophoblast invasion and an early sign of subsequently developing preeclampsia, eclampsia, and HELLP syndrome.

Objective: To investigate the expression of cyclooxygenase-2 (Cox-2) and vascular endothelial growth factor (VEGF) in ovarian endometriotic cysts and assess their relation with angiogenesis., Design: Experimental clinical study., Setting: University hospital., Patient(s): Fifty patients with ovarian endometriotic cysts., Intervention(s): Surgical excision of 50 ovarian endometriotic cysts., Main Outcome Measure(s): Microvessel density and the expression of Cox-2 and VEGF were analyzed immunohistochemically., Result(s): Cyclooxygenase-2 immunoreactivity was mainly cytoplasmic in glandular epithelial cells in all of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 21 (42%), and high expression in 17 (34%). Vascular endothelial growth factor immunoreactivity was mainly cytoplasmic in stromal cells in 46 (92%) of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 18 (36%), and high expression in 16 (32%). No immunoreactivity was present in 4 cases (8%). Both Cox-2 (r = 0.728) and VEGF (r = 0.670) were closely, statistically significantly related with microvessel density in ovarian endometriotic cysts. Cyclooxygenase-2 and VEGF also were highly statistically significantly correlated (r = 0.777) with each other., Conclusion(s): We observed Cox-2 expression mostly in glandular epithelial cells of ovarian endometriotic cysts, whereas VEGF expression was observed mainly in stromal cells. Cyclooxygenase-2 and VEGF were closely correlated with each other, and both of them appear to play a role in the angiogenesis of ovarian endometriosis.

Vascular endothelial growth factor (VEGF) serum levels and VEGF and cellular expression were prospectively analyzed in 60 patients (group A consisted of asymptomatic patients or patients presenting mild dysmenorrhea; 30 women comprised group B severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among VEGF serum levels, VEGF cellular expression, and pelvic pain. No differences were found in VEGF serum levels and VEGF cellular expression between both groups. Therefore, we conclude that pain symptoms in ovarian endometriosis are not correlated with VEGF serum levels and VEGF cellular expression.

Objective: To investigate the expression of oxytocin receptor (OTR) in peritoneal and ovarian endometriotic lesions., Design: Retrospective nonrandomized study., Setting: University hospital endometriosis research center., Patient(s): Premenopausal women with histologically confirmed endometriosis were selected. Peritoneal endometriotic lesions (n = 120); ovarian endometriotic cysts (n = 40); peritoneal biopsies, distant from the endometriotic lesion (n = 55); and unaffected peritoneal biopsies from patients without endometriosis (n = 11) were obtained. Hysterectomy specimens from patients without endometriosis and/or adenomyosis were used for controls (n = 10)., Intervention(s): Histopathological examination of peritoneal and ovarian specimens for OTR expression and identification of smooth muscle cells by immunohistochemistry staining with antibodies against OTR and smooth muscle actin. In addition, Western blot analysis, double-immunofluorescence, and in vitro studies with primary cell cultures have been performed., Main Outcome Measure(s): Comparison of the immunoreactive score of the OTR and smooth muscle actin expression with the smooth muscle content in peritoneum with and without endometriosis., Result(s): In the epithelial cells of endometriotic lesions, we could demonstrate a high OTR expression. The stromal cells were OTR negative with the exception of some single cells. By using a monoclonal anti-smooth muscle actin antibody, these cells could be identified as intrastromal OTR-positive smooth muscle cells. The peritoneum of women with endometriosis shows a significantly higher smooth muscle content than the peritoneum of women without endometriosis. There were no significant differences between the smooth muscle content of active or inactive lesions and the stage of disease., Conclusion(s): Oxytocin receptor is expressed in smooth muscle cells and epithelial cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. The inhibition of OTR by specific inhibitors might be a useful approach for the treatment of endometriosis-associated pain.

Objective: To compare immunohistochemical staining patterns in noncystic and cystic endometriosis lesions., Design: Experimental., Setting: Archived pathology material in an academic research environment., Patient(s): Endometriosis tissues from the pathology archives including slide tissue sections and blocks., Intervention(s): None; this was a retrospective study., Main Outcome Measure(s): Immunohistochemical staining of the tissues was performed using anti-bcl-2, anti-p53, anti-matrix metalloproteinase IX, and anti-collagen VI antibodies. Staining was qualitatively assessed in terms of extent and intensity., Result(s): p53 showed no staining in both groups. Anti-bcl-2 stained 100% (30/30) of endometriosis lesions compared with only 23% (7/30) of endometriotic cysts (P<.0001), and anti-matrix metalloproteinase IX stained 85% (23/27) of endometriosis lesions and only 39% (14/36) of endometriotic cysts (P=.0003). Anti-collagen VI, however, stained only 6% (2/35) of endometriosis lesions and 75% (21/28) of endometriotic cysts (P<.0001)., Conclusion(s): Compared with endometriosis lesions, endometriotic cysts display different expression of proteins with relative overexpression of collagen VI and underexpression of bcl-2 and metalloproteinase IX. This report is the first comparative immunohistochemical study showing these differences.

Objective: To determine the levels of the angiogenic factors vascular endothelial growth factor (VEGF) and interleukin (IL-8) in ovarian cysts., Design: Prospective descriptive study., Setting: University hospital., Patient(s): One hundred women, of whom 9 had ovarian carcinomas, 38 had ovarian endometriomata, 43 had serous ovarian cysts, and 10 had follicular ovarian cysts., Intervention(s): Sampling of serum and ovarian cystic fluid before and during surgery., Main Outcome Measure: Levels of VEGF and IL-8 in cystic fluid and serum., Result(s): Levels of both VEGF and IL-8 were found to be significantly higher in the cystic fluid of ovarian carcinomas and endometriomata than in serous and follicular cysts. In endometriomata fluid, levels of VEGF and IL-8 were found to be directly correlated (r = 0.68; P=.0074). Serum levels of VEGF were significantly higher in women with ovarian carcinomas and endometriomata than in those with serous and follicular cysts. Ovarian cancers and endometriomata were similar in terms of cystic concentrations of VEGF and IL-8 and in serum levels of VEGF., Conclusion(s): An increase in angiogenic factors that differentiate ovarian carcinomas and endometriomata from other kinds of ovarian pathology is demonstrated.

Objective: To evaluate the expression of inhibin A and activin A in ovarian endometriosis., Design: Uncontrolled cross-sectional study and controlled prospective in vitro study., Setting: Academic health centers in Siena, Udine, Sassari, and Milan, Italy., Patient(s): A group of women (n = 19) who underwent laparoscopic excision of ovarian endometriotic cysts., Intervention(s): Specimens of serum, peritoneal fluid, and cystic fluid, ovarian tissue for immunohistochemistry, and endometriotic cells for primary culture were collected. Cell cultures were also prepared from proliferative endometrium of women without endometriosis., Main Outcome Measures: Dimeric inhibin A and activin A concentrations in biological fluids; immunostaining of alpha and betaA subunits in ovarian endometrioma; alpha and betaA gene expression in cultured endometriotic cells compared with normal endometrium., Result(s): Inhibin A and activin A concentrations in the cystic fluid were slightly higher than in peritoneal fluid and significantly higher than in serum (P<.05). Immunoreactive alpha and betaA subunits were strongly expressed both in the epithelial and stromal components of ovarian endometrioma. The relative abundance of betaA mRNA was significantly decreased in endometriotic cells compared with eutopic stromal cells., Conclusion(s): The results of the present study provide evidence for a local production and secretion of inhibin A and activin A in ovarian endometriotic cysts.

Objective: To evaluate the effect of chocolate cyst fluid on the proliferation of cultured human endometrioma cells and to assay the concentration of transforming growth factor-B1 in this fluid., Design: Controlled in vitro study., Setting: Department of Obstetrics and Gynecology, State University of New York Health Science Center., Patient(s): Five women with ovarian endometriomas., Intervention(s): Endometrioma tissue and chocolate fluid from five different patients were entered in this study., Main Outcome Measure(s): Endometrioma cell proliferation in culture with and without chocolate cyst fluid., Result(s): Chocolate cyst fluid increased the proliferation of endometrioma cells compared with controls. Also, high concentrations of transforming growth factor-B1 were found in cysts' fluid., Conclusions: Chocolate cyst fluid has a growth-enhancing effect on endometrioma cells. One promoting growth factor is transforming growth factor-B1.

Gonadotropin levels and secretory patterns were studied in 28 oligomenorrheic patients with various types of polycystic ovary disease (PCO). On the basis of ovarian morphology and histology, the patients PCOuld be separated into two distinct categories arbitarily designated "typical" (type I) and "atypical" (type II) PCO. Although no differences were noted in symptomatology or 17-ketosteroid, testosterone, or follicle-stimulating hormone levels, the 12 type I patients demonstrated widely fluctuating, but markedly elevated, luteinizing hormone (LH) levels, while the 16 type II patients demonstrated lower and less fluctuating LH levels which were comparable to those found during the normal follicular phase. It is likely that type I PCO is a distinct entity similar to that described by Stein and Leventhal, while type II co represents a heterogenous spectrum of disorders, many of which remain obscure.