“Centers of excellence in endometriosis surgery” or “centers of excellence in endometriosis”

Centers of excellent endometriosis surgery could improve the care of women with endometriosis, especially if combined with control of the quality of the surgery performed, e.g., through systematic taping of entire interventions. Centers of excellence in endometriosis without emphasis on providing excellent surgery seem of little value and could do more harm than good.     

Leptin concentrations in the peritoneal fluid of women with ovarian endometriosis are different according to the presence of a ‘deep’ or ‘superficial’ ovarian disease

Some studies have suggested a possible role of leptin, an active cytokine produced by adipocytes, in the pathogenesis of pelvic endometriosis. The present study was designed to assess leptin levels in the peritoneal fluid (PF) of women with the ‘deep’ or ‘superficial’ types of ovarian endometriosis. Twenty-seven women with a single ovarian endometrioma having a mean diameter between 3 and 5 cm were included in the study. Patients were divided into two groups according to the type of ovarian endometriosis: Group A (n = 11) consisted of women with ‘superficial’ endometriomas located at the ovarian surface; Group B (n = 16) included patients with ‘deep’ intra-ovarian endometriomas. Women undergoing laparoscopy for unexplained infertility and not affected by pelvic and/or ovarian endometriosis were considered as controls (Group C, n = 10). Patients with an ovarian endometrioma had significantly increased PF leptin concentrations than endometriosis-free controls (Groups A and B vs. Group C, p < 0.01). Patients with ‘superficial’ endometriomas had significantly higher PF leptin levels compared with patients with ‘deep’ endometriomas (Group A vs. B, p < 0.01). This difference remained significant after correction for the BMI; moreover, a positive correlation between PF leptin and BMI was observed in Groups B and C, but not in women with ‘superficial’ endometrioma (Group A). Our observations suggest that: (a) leptin could play an active role in promoting the development of ‘superficial’ ovarian endometriomas and (b) ‘superficial’ and ‘deep’ ovarian endometriomas could have a different pathogenesis.     

Role of estrogen receptor-β in endometriosis

Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.     

Expression of human β-defensin-2 in the eutopic and ectopic endometrial tissues in patients with endometriosis

Objective

To investigate the expression of human β-defensin-2 (hBD-2) in the endometrium of patients with endometriosis (EMS) and explore the potential role of hBD-2 in the pathogenesis of EMS.

Design

Prospective controlled study.

Sample

50 women including EMS patients undergoing laparoscopic ovarian cystectomy and non-EMS patients undergoing hysterectomy for uterine fibroids.

Setting

Large university teaching hospital.

Methods

Patients were divided into EMS and non-EMS groups. The gene expressions of hBD-2, interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the endometrial tissues of each group were detected with real-time quantitative polymerase chain reaction (PCR), and hBD-2 protein expression with immunohistochemical method.

Results

The gene expression levels of hBD-2, TNF-α, and IL-1β as well as the positive expression rate of hBD-2 protein in the ectopic endometrium of EMS patients were significantly higher than those in the eutopic endometrium of EMS and non-EMS patients (all P < 0.05). Correlation analysis showed that the gene expression levels of hBD-2 in the ectopic and eutopic endometrium of EMS patients were positively correlated with the gene expression levels of IL-1β and TNF-α (P < 0.01).

Conclusion

High levels of hBD-2 gene and protein expressions in the ectopic endometrium of EMS patients may be an important contributor in the pathogenesis of EMS. TNF-α and IL-1β may promote the upregulation of hBD-2 expression.     

Plasma and follicular fluid concentrations of LHRH antagonist cetrorelix (Cetrotide®) in controlled ovarian stimulation for IVF

Cetrorelix was administered in differing daily dosages for controlled ovarian stimulation. The dosage levels were 3 mg (9 cycles), 1 mg (19 cycles), 0.5 mg (43 cycles), 0.25 mg (46 cycles) and 0.1 mg (7 cycles). In the 3 mg, 1 mg and 0.5 mg group the respective median plasma concentrations of cetrorelix on the day of oocyte pick-up (OPU) were 2.10 ng/ml, 1.42 ng/ml and 0.88 ng/ml and 1.03 ng/ml, 0.46 ng/ml and 0.49 ng/ml on the day of embryo transfer (ET). In the 0.25 mg and 0.1 mg groups plasma cetrorelix levels were below the limit of quantification. The cetrorelix concentrations in follicular fluid (FF) in the 0.25 mg group were detec- table in only 14 out of 44 samples, while in the 0.1 mg group no detectable concentrations could be obtained. We also examined 80 cycles after single doses of 5 mg (7 cycles), 3 mg (42 cycles), and 2 mg (31 cycles) cetro-relix. On the day of OPU the respective median plasma concentrations of cetrorelix were 0.57 ng/ml, 0.62 ng/ml, and 0.56 ng/ml, and 0.61 ng/ml and 0.28 ng/ml on the day of ET in the 5 mg and 3 mg groups. In the 2 mg group, the plasma concentrations fell to below limits of quantification in 8/9 samples on the day of ET. In 26 out of 27 FF samples cetrorelix was detectable in the 3 mg single dose group (median level: 0.69 ng/ml). Received: 24 November 2000 / Accepted: 19 February 2001     

Correlation of changes of (non)exfoliated endometrial organelles and expressions of Musashi-1 and β-catenin with endometriosis in menstrual period

This study aims to investigate the correlation of structural changes of endometrial organelles and expressions of Musashi-1 (Msi-1) and β-catenin with the endometriosis (EMs) in the menstrual period. The structural changes of exfoliated and nonexfoliated endometrial organelles in the experimental group and the control group were observed by the transmission electron microscopy (TEM) on the first and fifth day of menstruation. (1) TEM: compared with the control group, the exfoliated endometrial organelles in the experimental group on the first day were rich, with irregular nucleus, the bi-nucleolus could be seen, with rich chromatin; while the shapes of epithelial secretory cells in the nonexfoliated endometrial gland were irregular, with abundant organelles, the basal film varied in width, with abnormal curvature, and a lot of intercellular collagen fibers could be seen. (2) The expressions of Msi-1 and β-catenin in the exfoliated and nonexfoliated endometrium of the experimental group were higher than those of the control group and exhibited positively correlation, while no correlation could be found within the control group. (1) The organelles’ structural changes might cause the changes of endometrial cellular functions. (2) Msi-1 might participate in the formation of EMs through activating the Wnt/β-catenin signaling pathway.     

The role of TGFβ superfamily members in the pathophysiology of endometriosis

Abstract

The transforming growth factor-beta (TGFβ) superfamily comprises over 30 dimeric proteins with conserved structures, which play important roles in the control of cellular proliferation, differentiation and apoptosis. These proteins are expressed and finely regulated in human endometrium during the menstrual cycle, which is consistent with their effects on endometrial cell proliferation and tissue remodeling. This review is focused on summarizing the role of key members of the TGFβ superfamily in the pathophysiology of endometriosis. Evidence suggests that TGFβ, activins, inhibins, nodal, bone morphogenetic proteins, growth differentiation factors, and anti-Müllerian hormone are produced by endometriotic lesions and could be involved in the establishment and progression of the disease. Their receptors and signaling pathways may also be altered in the presence of endometriosis and may be potential targets to the development of therapeutic agents.     

Polypoid endometriosis – A rare entity of endometriosis mimicking ovarian cancer

ObjectiveTo report a rare case of polypoid endometriosis with initial impression of ovarian cancer and review the published literature about this disease.Case reportA 23-year-old female presented with sudden onset of acute lower abdominal pain. Image studies revealed an irregular shaped, heterogeneous mass at the cul-de-sac, but without ascites or enlargement of pelvic or paraaortic lymph nodes. Blood tests showed an elevated CA-125 value (1317 U/ml). Resection of the mass was performed by laparotomy and the frozen section and final pathology both revealed polypoid endometriosis. Post-operative gonadotropin-releasing hormone agonist was given for 6 months followed by oral contraceptives. She remained disease free 3 years after operation.ConclusionPolypoid endometriosis is an uncommon and distinctive variant of endometriosis. Gynecologists should be aware of this rare form of a commonly benign disease to avoid excessive resection in younger patients of childbearing age.     

Complex congenital malformations and the impact of the plasminogen activator system and β-hCG in amniotic fluid

Objective

The plasminogen activator system and β-hCG may affect neural crest cells and angiogenesis, and thereby embryogenesis. Therefore, we investigated these parameters in amniotic fluids of pregnancies with a complex congenital malformation.

Study design

In a case-control study amniotic fluid samples were collected from 62 pregnancies with a complex congenital malformation and from 110 healthy control pregnancies at an obstetric department of a large university hospital in the Netherlands. We determined concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitors (PAI-1, PAI-2), tPA∼PAI-1 and uPA∼PAI-1 complexes, and β-hCG with enzyme-linked immunosorbent assays. Mann–Whitney U-tests and analysis of covariance, adjusting for gestational and maternal age, were performed for data comparisons.

Results

Compared with controls, cases demonstrated significantly lower adjusted geometric mean levels of uPA (24%), tPA (≥19%) and tPA∼PAI-1 (35%). Cases showed significantly higher adjusted mean levels of β-hCG (≥48%) and PAI-2 (10 ng/mL) than controls. Mean PAI-1 and uPA∼PAI-1 levels were comparable between both groups.

Conclusions

Disturbances in the plasminogen activator system and β-hCG levels are suggested to be involved in the pathogenesis of complex congenital malformations by affecting neural crest cell migration and angiogenesis.     

Combination of polymorphisms in luteinizing hormone β, estrogen receptor β and progesterone receptor and susceptibility to infertility and endometriosis

Objectives

To determine whether the combination of PR (PROGINS), ERβ G + 1730A and/or LHβ G1502A polymorphisms in infertile women with and without endometriosis and in a control group increases the risk of infertility and/or endometriosis.

Study design

Case-control study including 201 infertile women with endometriosis, 80 infertile women without endometriosis and 206 fertile women as control group. PROGINS was identified by PCR (polymerase chain reaction) and ERβ G + 1730A and LHβ G1502A were identified by PCR-RFLP (restriction fragment length polymorphism).

Results

A statistically significant difference was found for the combination of LHβ + ERβ polymorphisms among infertile patients with endometriosis and control group (p = 0.003, OR = 2.468), among infertile patients with endometriosis I/II and control group (p = 0.002, OR = 3.081), among infertile patients with endometriosis III/IV and control group (p = 0.035, OR = 2.136) and for the combination of LHβ + PROGINS polymorphisms among infertile patients with endometriosis I/II and control group (p = 0.014, OR = 3.081). However, the odds of developing endometriosis are not enhanced in the presence of the two polymorphisms, being similar to the odds when only LH polymorphism is present.

Conclusions

Individually, the presence of LHβ G1502A and ERβ G + 1730A polymorphisms is associated with infertility and endometriosis associated infertility. However, when two polymorphisms are present in the same individual it does not appear to increase the chance of developing endometriosis or infertility.