Background Endometriosis, the presence of endometrial-like tissue outside the uterus, is a common clinical entity between women of reproductive age, with a prevalence of about 10%. Due to the variety of endometriosis-associated symptoms, a great variety of treatments have been implemented. The aim of this review is to give an overview on therapeutical approaches of eight national and international widely used guidelines. Methods Six national (College National des Gynecologues et Obstetriciens Francais, National German Guideline (S2k), Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians (ACOG) and Gynecologists, American Society for Reproductive Medicine (ASRM) and National Institute for Health and Care (NICE) and two international (World Endometriosis Society, European Society of Human Reproduction and Embryology) guidelines are included in this review. Conclusion All the above-mentioned guidelines agree that the combined oral contraceptive pill, progestogens are therapies recommended for endometriosis associated pain. Concerning infertility, there is no clear consensus about surgical treatment. Discrepancies are also found on recommendation of the second- and third-line treatments.

Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n ¼ 136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n ¼ 3/20, 15%) and one deep-infiltrating endometriosis sample (n ¼ 1/22, 5%), but in none of the peritoneal endometriosis (n ¼ 0/16) and eutopic endometrium samples (n ¼ 0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (Po0.0005), as well as peritoneal (P ¼ 0.003) and deep-infiltrating endometriosis (P ¼ 0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.

Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS + standard deviation) was 7.6 + 2.5 in endometriosis and 5.3 + 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 + 0.7 and 11.8 + 1.1 in endometriosis and 11.6 + 1.0 and 11.9 + 0.4 in normal endometrium (P ¼ .7 and P ¼ .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.

BackgroundThe G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors.MethodsA tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS < 6) and high (IRS > =6) expression groups.ResultsThe mean epithelial IRS (+/−standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/−1.7, 0–4) in normal endometrium and 5.1 (+/−3.5, 0–12) in endometriosis (p < 0.001), of nuclear GPER 6.4 (+/−2.6, 0–12) and 6.8 (+/−2.9, 2–12; p = 0.71), of ER-alpha 10.6 (+/−2.4, 3–12) and 9.8 (+/−3.0, 2–12; p = 0.26), of ER-beta 2.4 (+/−2.2; 0–8) and 5.6 (+/−2.6; 0–10; p < 0.001), and of PR 11.5 (+/−1.7; 3–12) and 8.1 (+/−4.5; 0–12; p < 0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/−3.0; 2–12) in endometrium and 10.8 (+/−1.7; 6–12) in endometriosis (p < 0.001), of ER-alpha 8.7 (+/−3.1; 2–12) and 10.6 (+/−2.4; 2–12; p = 0.001), of ER-beta 1.8 (+/−2.0; 0–8) and 5.4 (+/−2.5; 0–10; p < 0.001), and of PR 11.7 (+/−0.9; 8–12) and 10.9 (+/−2.0; 3–12; p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p < 0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p < 0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium.ConclusionsThe present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.

Venous thromboembolism (VTE) in pregnancy, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major factor of maternal mortality. Several patient-specific risk factors along with the physiologic changes of pregnancy promote a state of hypercoagulability in pregnant women. Detailed assessment of all pregnant women can establish a risk profile that would guide clinical decisions, and balance potential therapeutic benefits with side effects. Differentiating between physiologic changes of pregnancy and symptoms of VTE can be challenging and warrants meticulous clinical evaluation. Timely and accurate diagnosis of VTE with proper imaging is essential for its management, and systemic anticoagulation remains the cornerstone of VTE prevention and therapy. Furthermore, advanced invasive treatment options such as inferior vena cava filters and thrombectomy can be considered for complex cases. Importantly, the risk of systemic anticoagulation should be balanced against the risk of VTE-associated morbidity and mortality for mother and fetus, and an informed decision should be made. In this review, we present an up-to-date overview of VTE management in pregnancy and the postpartum period.