Murat Ulukus

THE ROLE OF ENDOMETRIUM IN ENDOMETRIOSIS

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Several theories have been proposed to explain the pathogenesis of this disease. According to Sampsons retrograde menstruation theory, endometrial cells are refluxed through the fallopian tubes during the menstruation and implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very common phenomenon among women of reproductive age, there must be other factors that may contribute to the pathophysiology and/or pathogenesis of endometriosis. Genetic predisposition, environmental factors, and alterations in immune and endocrine functions are believed to play significant roles in the establishment and maintenance of endometriosis. Although the eutopic endometriums of women with and without endometriosis are histologically similar, studies revealed that there are many fundamental differences between these two tissues. Invasive properties, decreased apoptosis, alterations in expression of specific gene and proteins, and increased steroid and cytokine production have been identified in eutopic endometrium of women with endometriosis. Furthermore, significant biochemical differences exist even between ectopic and autologous eutopic endometrium. These differences can be explained by the direct effects of an inflammatory peritoneal environment.

Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis

OBJECTIVE To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis. DESIGN Comparative immunohistochemical study. SETTING Academic medical center. PATIENT(S) Ectopic (n = 24) and homologous eutopic endometrium (n = 24) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of IL-8 and MCP-1. INTERVENTION(S) Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies. MAIN OUTCOME MEASURE(S) Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium. RESULT(S) In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium. CONCLUSION(S) These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.

Primary pelvic hydatid cyst

Abstract We report a case of hydatid cyst of the pelvis in a 36-year-old woman presented with right adnexal cystic mass with similar cystic lesions in the liver. Laparatomy revealed a right paraovarian cystic mass densely adhered to the uterus, to the pelvic side wall, and to the right fallopian tube. Histopathological examination of the cyst wall showed the cuticular layer of the cyst. Cystic liver lesion was later proved to be hepatic hemangioma by magnetic resonance imaging.

Initial endometriosis showing direct morphologic evidence of metaplasia in the pathogenesis of ovarian endometriosis

Summary: It is believed that ovarian endometriosis may be generated by a celomic metaplastic process from existing epithelium in the ovary. However, no morphologic evidence of metaplastic process has been described. In this study, we intended to identify the earliest morphologic changes of endometriosis within the ovary to examine if evidence of metaplasia exists. Included in this study were 110 ovarian endometriosis cases and 30 benign ovaries without endometriosis but with ovarian epithelial inclusions (OEIs). Among the 110 well-established ovarian endometriosis cases, 34 cases showed areas of initial endometriosis (IE), which is defined as lesions showing direct transitions from normal-looking ovarian tissue to areas of minimal formation of endometriosis and/or to areas of full-blown endometriosis. We further divided IE into two types: type I IE was present on the ovarian surface, which was associated with ovarian surface epithelia; type II was located within the ovarian cortex, which was associated with OEIs. Sections containing IE, OEIs, and well-formed endometriosis were subject to CD10 and aromatase immunostaining. In IE lesions, the number of CD10-positive cells were significantly higher than the number of that in OEIs, but lower than that of well-formed endometriosis areas (p < 0.05). Aromatase expression was detected in both epithelial and stromal components of the IE lesions, indicating that estrogen local production may be involved in this initial process of endometriosis. Microvessel density was higher in IE lesions than in areas of OEI (p < 0.05). Based on the morphologic characteristics of IE, we believe that IE represent a spectrum of the earliest morphologic changes of endometriosis identifiable by routine microscopy. The morphologic transitions from ovarian surface epithelium or OEI to IE lesions provide direct metaplastic evidence for the pathogenesis of ovarian endometriosis. This metaplastic process may not only involve the ovarian epithelial cells, but also stromal components. Local production of estrogen, probably in high-levels, may be related to the initial process of endometriosis, although detailed mechanisms remain to be clarified.

Regression of Endometrial Implants by Resveratrol in an Experimentally Induced Endometriosis Model in Rats

Objective: To evaluate the effect of resveratrol on an experimentally induced endometriosis rat model. Study design: After endometriotic implants were surgically formed, rats were randomly divided into 2 groups as control group (saline treated, n = 6) and resveratrol group (10 mg/kg/d, n = 6). The inflammatory markers and histopathological changes were assessed at the end of the treatment period. Results Our results showed (1) significant reduction in the implant size (P < .0005); (2) significantly decreased levels of vascular endothelial growth factor (VEGF) in the peritoneal fluid and plasma (P < .005); and monocyte chemotactic protein 1 (MCP-1) in the peritoneal fluid (P < .05), (3) highly significant suppression of VEGF expression in the endometriotic tissue (P < .0005); and (4) considerable histological changes in the endometriotic foci following resveratrol treatment. Conclusion: Resveratrol appears to be effective on the development of endometriosis through its antiangiogenic and anti-inflammatory properties. Future studies with different doses of resveratrol might provide more comprehensive results regarding the treatment of endometriosis.

Bilateral metastatic carcinoma of the breast from primary ovarian cancer.

Abstract We report a case of ovarian cancer with metastasis to both breasts and axillary lymph nodes and the vaginal cuff. A 41-year-old previously hysterectomized women presented with pelvic mass and malignant pleural effusion. During the courses of chemotherapy; bilateral breast nodules, and bilateral axillary lymphadenopathies and a nodule in the vaginal cuff were identified. The biopsy of both breasts, axillary lymph nodes and the nodule in the vaginal cuff revealed papillary serous cystadenocarcinoma. Immunohistochemical staining of breast specimens were positive for ovarian tumor marker CA-125.

Bilateral Jugular Venous Thromboembolism and Pulmonary Emboli in a Patient with Severe Ovarian Hyperstimulation Syndrome

We report here a case of severe ovarian hyperstimulation syndrome with massive ascites in a 25‐year‐old woman with a history of primary infertility after an IVF‐ET cycle. At the 9th gestational week she presented with neck pain and dyspnea and duplex Doppler sonographic examination of the neck veins revealed bilateral jugular venous thrombosis. Despite prompt administration of low‐molecular weight heparin, pulmonary emboli developed a few days later.

Regulation of Monocyte Chemotactic Protein-1 Expression in Human Endometrial Endothelial Cells by Sex Steroids: A Potential Mechanism for Leukocyte Recruitment in Endometriosis

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 × 10— 8 mol/L), progesterone (10—7 mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase—polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Long-term use of gonadotropin-releasing hormone analogues before IVF in women with endometriosis.

Purpose of review To discuss the relationship between endometriosis and infertility, the impact of endometriosis on assisted reproductive techniques and also the benefits of prolonged use of gonadotropin-releasing hormone analogue before IVF in women with endometriosis. Recent findings The available evidence suggests that endometriosis is strongly associated with infertility. Many studies indicate lower pregnancy and implantation rates even in assisted reproductive cycles in women with endometriosis. It is well known that medical suppression of endometriosis does not appear to be warranted for endometriosis-associated infertility. Prolonged pretreatment with gonadotropin-releasing hormone analogue before IVF has been reported to improve clinical pregnancy rates in infertile women with endometriosis. Summary Based on the recently published data, infertile women with endometriosis may benefit from long-term pretreatment of gonadotropin-releasing hormone analogue prior to IVF.

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles

Abstract  Objective:To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. Materials and methods:One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients’ files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. Results:The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=–0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=–0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles ≥18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles ≥18 mm and 24% with ≥4 follicles ≥18 mm. Conclusion: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles.