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[Expression of heparanase gene in eutopic and ectopic endometrium of women with endometriosis].

OBJECTIVE: To study the function of heparanase gene in the pathogenesis of endometriosis. METHODS: In situ hybridization method was used to examine the heparanase mRNA expression in the eutopic and ectopic endometrium of patients with endometriosis (EM group, 23) and the eutopic endometrium of women without endometriosis (control group, 25). RESULTS: (1) In EM group: The frequency of heparanase gene expression in eutopic was similar to that in ectopic endometrium. However the number of positive cells and the intensity of heparanase gene expression in ectopic endometrium was more than that in eutopic endometrium. The frequency of heparanase gene expression in proliferative phase was 83.3% (10/12), while in secretory phase it was 72.7% (8/11), the difference is not significant; (2) In control group: The frequency of heparanase gene expression in proliferative phase was 41.7% (5/12), while in secretory phase it was 7.7% (1/13), the difference is significant; (3) The frequency of heparanase gene expression in endometrium of patients with endometriosis and women without endometriosis were 78.3% (18/23) and 24.0% (6/25) respectively, the difference is significant. CONCLUSIONS: Heparanase gene may play some roles in the pathogenesis of endometriosis, and it may participate the regulation of menstrual cycle, and that it may participate the regulation of menstrual cycle. It may be an important target of the trentment for endometriosis.

Endometriosis↗

[Etiopathogenesis of endometriosis related infertility].

In the last years the entire scientific community has devoted remarkable resources to the understanding of endometriosis. In spite of this, endometriosis remains one of the most complex gynecological diseases, in nearly all of its physiopathological aspects and implications. In particular, the association between endometriosis and infertility has proven to be complex and it has been widely discussed. It is generally accepted that moderate/severe endometriosis related sterility is due to mechanical factors, namely to the distortion/subversion of the regular pelvic anatomy. On the contrary, the factors behind infertility/subfertility related to minimal/mild endometriosis are less clear. None of the hypothesized mechanisms exhaustively explained the infertility related to endometriosis, while it is possible that such disease is caused by multiple factors altogether. The aim of this thorough review of the international literature is to analyze the main etiological factors (i.e. alterations in oocyte maturation and/or growth, defects of fertilization, impairments of implantation or aberrant immunological mechanisms) that are potentially involved, as well as the role that each of the above mentioned factors has in determining the endometriosis related infertility/subinfertility.

Adult↗

T allele for VEGF gene-460 polymorphism at the 5'-untranslated region: association with a higher susceptibility to endometriosis.

OBJECTIVE: To investigate whether vascular endothelial growth factor (VEGF) gene 5'-UTR-460 polymorphism could be used as a marker of susceptibility to endometriosis. STUDY DESIGN: Women were divided into 2 groups, endometriosis (n = 122) and nonendometriosis (n = 131). Polymorphisms for VEGF were detected by polymerase chain reaction and BstUI (New England Biolabs, Beverly, Massachusetts) restriction enzyme analysis. Genotypes and allelic frequencies between the groups were compared. RESULTS: Proportions of different VEGF polymorphisms in the groups were significantly different. Proportions of cuttable (C) homozygote/heterozygote/ uncuttable (T) homozygotefor VEGF in the groups were 0/44.3/55.7% and 0/63.4/36.6%, respectively. A higher percentage of T/F homozygote and T allele was present in the endometriosis population. The proportions of C/T alleles in the groups were 22.1/77.9% and 31.7/68.3%, respectively. CONCLUSION: T/T homozygotes and the T allele of the VEGF-460 gene are associated with a higher risk of endometriosis. Heterozygotes and C allele are related to the lower risk of endometriosis formation. VEGF polymorphism likely contributes to the pathogenesis of endometriosis and may become a useful markerfor predicting endometriosis susceptibility.

5' Untranslated Regions↗

Mononuclear cell beta-endorphin concentration in women with and without endometriosis.

Seventy-five consecutive patients undergoing laparoscopy for chronic pelvic pain and/or infertility were studied to test whether beta-endorphin concentrations in peripheral mononuclear cells differed according to the presence or absence of endometriosis. Endometriosis was diagnosed in 45 subjects (minimal in 24, mild in 11, moderate in four, and severe in six). Twenty-eight women (62%) with endometriosis and ten (33%) without the disease reported moderate or severe pelvic pain. beta-Endorphin levels were lower in the endometriosis group than in the controls (16.6 +/- 11.2 versus 21.9 +/- 10.5 pg/10(6) cells; P less than .01). This decrease was attributable to reduced beta-endorphin concentrations in the endometriosis patients with moderate or severe pain compared with symptomatic controls (15.5 +/- 10.0 versus 26.3 +/- 7.0 pg/10(6) cells; P less than .01). A significant difference was also found in relation to the cycle phase: The opioid concentration was reduced in the luteal phase in the endometriosis group compared with controls (14.4 +/- 8.4 versus 23.8 +/- 7.5 pg/10(6) cells; P less than .01), but no differences were demonstrated in the follicular and periovulatory phases. beta-Endorphin is capable of modulating the immune response and can be considered as a classical cytokine. Low beta-endorphin production during the luteal phase may have implications in the development and/or maintenance of endometriosis.

Adult↗

[Clinical study of effect of laparoscopic diagnosis and treatment on pelvic endometriosis-associated infertility].

OBJECTIVE: To investigate the role of laparoscopy in diagnosis and treatment of infertile women with endometriosis. METHODS: Totally 314 infertile cases were diagnosed as having endometriosis by laparoscopy, and 58, 173, 68 and 15 cases were assigned to stage I, II, III and IV groups respectively according to the revised classification American Fertility Society (r-AFS). Laparoscopic treatment included excision of ovarian endometriosis lesions, lysis of adhesions, endocoagulation of pelvic endometriosis lesions with controlled heating (100 degrees C) and lavaging of the peritoneal cavity. The duration of follow-up after laparoscopic surgery was censored at 36 weeks. Women who became pregnant were followed up to 20 weeks' gestation. The U and chi(2) tests were used to determine significance of difference in the rate of pregnancy and spontaneous abortion between all clinical stages. RESULTS: Of all the 314 cases, 254 became pregnant within 36 weeks after surgery. The cumulative numbers of pregnancy were 50 (86.2%, 50/58), 141 (81.5%, 141/173), 52 (76.5%, 52/68) and 11 (73.3%, 11/15) in stage I-IV groups respectively. The accumulative pregnancy rates were, however, not significantly different among stages I-IV (P > 0.05). The accumulative pregnancy rate within 24 weeks after surgery (93.7%, 238/254) was higher than that within 25 - 36 weeks after surgery (6.3%, 16/254). Of 254 cases who were pregnant, 12 had miscarriage. There was no significant difference of miscarriage rate between all stages (P > 0.05). While the rate of miscarriage was higher within 12 weeks of gestation (83.3%, 10/12) than that of after 12 weeks of gestation (P < 0.05). CONCLUSIONS: Early lesions of endometriosis and pelvic factors for infertility can be found by laparoscopy. And pregnancy rate of endometriosis-associated infertility can be improved by laparoscopic surgery. To clean the menstrual blood pool and ablate peritoneal lesion with endocoagulation as completely as possible have significant importance for enhancement of fecundity in infertile women with endometriosis, especially for stage I-II cases.

Abortion, Spontaneous↗

Lysosomal evaluation of endometrioma capsule epithelium and endometrium of patients with or without endometriosis.

OBJECTIVE: To evaluate the number of lysosomes in glandular epithelia of the endometrioma capsule and endometrium from patients with or without endometriosis using a histochemical method (acidic phosphate determination) under light microscopy. METHOD: We studied 31 selected patients with similar clinical features, except for the occurrence of menorrhagia enhanced in patients with endometriosis. All patients were submitted to video laparoscopic procedures and endometrial biopsies through hysteroscopy during the secretory phase. After surgery, the patients were divided into two groups for hysteroscopic data: GI--without endometriosis (control, n = 16) and GII--with endometriosis (n = 15). In GII, the lysosomes of the endometrioma were also counted (GIIa). RESULTS: The GI sample was comprised only of endometrial biopsies. We found that the number of lysosomes in the topic endometrial tissue of patients with endometriosis was significantly larger than the number in endometrioma. Also, there were more lysosomes in the endometrium of patients with endometriosis than in endometrioma-bearing patients. CONCLUSION: Our data suggest that variations in the number of lysosomes may underlie the pathogenesis of endometriosis.

Adult↗

[Expression of cylooxygenase-2 in endometriosis].

OBJECTIVE: To investigate the expression of cyclooxygense-2 (COX-2) in eutopic and ectopic endometrium in ovarian endometriosis. METHODS: Thirty patients with ovrian endometriosis, 10 with ovarian chocolate cysts and 27 normal controls were enrolled it determine the expression of COX-2 immunohistochemically in eutopic or ectopic endometrium or healthy endometrial tissues. RESULTS: The immunoreactivities of COX-2 were found in epithelial cells and stromal cells in eutopic endometrium. The expression of COX-2 in the epithelial cells in the secretory phase was higher than that in the proliferative phase in the control group and ovarian endometriosis group (P <0. 05). But the expression of COX-2 in stromal cells in the control group and ovarian endometriosis group showed no cyclic changes throughout the menstrual cycle (P > 0. 05). The expression of COX-2 in eutopic and ectopic endometrium in the ovarian endometriosis group was higher than that in the control group (P <0. 05) , hut we did not find significant difference between the eutopic and ectopic endometrium in the ovarian endometriosis group (P > 0. 05). CONCLUSION: The increased COX-2 expression in eutopic and ectopic endometrium in ovarian endometriosis may he related to its pathology.

Adult↗

[Effect of dietary supplementation with eicosapentaenoic acid on surgically induced endometriosis in the rabbit].

The association between endometriosis and infertility is well known. Recently some investigators have speculated that endometriosis may cause an inflammatory response and prevention of normal fertilization, embryo development or implantation. Eicosapentaenoic acid (EPA) inhibits production of cyclooxygenase metabolites of arachidonic acid (AA). The effect of oral administration of pure EPA on endometriosis was studied. The author supplemented the diet of Japanese white rabbits with EPA (100 mg/kg/day, experimental group) or with a 5% gum arabic solution (control). Endometriosis was surgically induced by a previously described experimental technique. Peritoneal fluid PGE2, PGF2-alpha and IL-1-beta concentrations in the experimental rabbits and controls were measured before and after induction of endometriosis by laparotomy. Following the treatment, EPA levels in plasma and peritoneal fluid increased significantly. However, no differences were seen in AA levels. Peritoneal fluid PGE2 and IL-1-beta concentrations increased significantly after induction of endometriosis in the control group. In contrast, they were not significantly changed after endometrial implantation in the experimental group. Peritoneal fluid PGF2-alpha concentrations were lower in the EPA group than in the controls, but there were no significant differences. The findings of the present study suggest the beneficial effects of EPA in the therapy of infertile patients with endometriosis.

Administration, Oral↗

Menstrual cyclicity of CA-125 in patients with endometriosis.

OBJECTIVE: To examine the serum levels of CA-125 in the menstrual, follicular, and luteal phases of the menstrual cycle in women with endometriosis and to determine if serum CA-125 levels drawn during menses improve the clinical utility of the test in diagnosing endometriosis. DESIGN: Serum CA-125 was measured in the menstrual, follicular, and luteal phases of the cycle preceding surgery. CA-125 levels for each phase were categorized by postoperative diagnosis and endometriosis stage. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: A total of 65 patients were recruited from the Fertility and Endocrine Unit and the Gynecology Service of Brigham and Women's Hospital. MAIN OUTCOME MEASURE: Serum CA-125 levels were measured by an immunoradiometric assay and were stratified by menstrual cycle phase, diagnosis, and stage of endometriosis. The menstrual cycle phase was confirmed by serum estradiol and progesterone measurements. RESULTS: Serum CA-125 levels in patients with stages II to IV endometriosis were significantly elevated in the menstrual phase compared with levels drawn in the nonmenstrual follicular and luteal phases. The sensitivity and specificity of CA-125 for the diagnosis of endometriosis were not significantly better in the menstrual than in the follicular or luteal phases. CONCLUSIONS: Despite menstrual cyclicity of CA-125, measurement of serum CA-125 during menses does not improve the clinical utility of the test in the diagnosis of endometriosis.

Antigens, Tumor-Associated, Carbohydrate↗

[Specifics of therapy of tubal infertility in patients with endometriosis].

Our purpose was to define the best way of treating tubal infertility caused by endometriosis. We have studied 24 patients with tubal infertility caused by endometriosis; the etiology has been laparoscopically established in the 2nd Clinic of Obstetrics and Gynecology Iaşi. The endometriosis score (r-AFS) was used to establish the therapy. We performed laparoscopic treatment when endometriosis was visible. Postoperative medical therapy (Diphereline, 3 months) was indicated; patients with ,,unpigmented endometriosis" received the same medical therapy. The rate of pregnancies in patients that had benefit of combined therapy: surgical and medical (n=9) was superior (44.4%) to that obtained in patients that were only surgical treated (n=15): 26.6% (Spearman correlation--0.6595, p < 0.0012). Endometriosis is an important etiological factor in female infertility. The pathway is mechanic as well as chemical and it justifies the combined therapy. There are better results, as fertility prognosis in patients with endometriosis that receive both, surgical and medical therapy.

Adult↗

[Endometriosis and deficient intake of antioxidants molecules related to peripheral and peritoneal oxidative stress].

OBJECTIVE: To evaluate the antioxidant intake and the lipoperoxidation status in plasma and peritoneal fluid of women with endometriosis. PATIENTS AND METHODS: The study was carried out in 48 women with endometriosis obtained at the Sterility Clinic from the National Institute of Perinatology. The antioxidant intake was evaluated applying the Questionnaire Assessment of Antioxidants and Retinol Intakes in Mexican women validated by the National Institute of Public Health. The lipoperoxidation status was determined in plasma and peritoneal fluid with the malondyaldehyde method. Results were analyzed by ANOVA of Kruskal-Wallis. RESULTS: The antioxidant intake (vitamin C, vitamin E, selenium and zinc) of women with endometriosis showed a significative statistical difference when data was compared with the control group, including total group and those stratified in pathology stages. The lipoperoxidation status in plasma and peritoneal fluid of women with endometriosis, analyzed in group, did not show statistical difference versus healthy women. When data was stratified according to the pathology severity, the percentage of lipoperoxidation status increased in plasma in the severe grade of endometriosis and in peritoneal fluid in the moderate and severe grades. CONCLUSIONS: The antioxidant intake in women with endometriosis showed an inverse correlation with the pathology intensity. As endometriosis severity intensifies, a less intake of antioxidants is present. There is a positive association between the pathology development and the lipoperoxidation status.

Adult↗

Endometriosis and infertility: a review.

The objective of this article is to review the current understanding of the relationship between endometriosis and infertility and the recommended management based on the latest evidence. The article is based on a MEDLINE search and bibliography review of the relevant literature from 1960 to 2003. The exact nature of the relationship between endometriosis and infertility remains uncertain. Surgical treatment of moderate and severe endometriosis improves the monthly fecundity rate. Surgical ablation of minimal and mild endometriosis seems superior to expectant management. Infertile patients with minimal and mild endometriosis can benefit from using clomiphene citrate and intrauterine insemination (IUI) or gonadotropins and IUI. Ovarian suppression should not be used in asymptomatic patients wishing to become pregnant except in the setting of in vitro fertilization and embryo transfer (IVF/ET). Prolonged suppression with gonadotropic-releasing hormone analogues should be considered for endometriosis patients about to undergo an IVF/ET cycle. IVF seems to be effective in endometriosis patients.

Adult↗

Endometriosis impairs glycogen synthesis in human endometrium.

Glycogen content in endometrium with endometriosis was about half of that without endometriosis at the secretory phase, whereas no difference was found in the proliferative phase. The activity of glycogen synthetase in endometrium with endometriosis was reduced to 25% and 23% of that without endometriosis in the late proliferative and midsecretory phase, respectively. The activity of glycogen phosphorylase was also significantly lower in endometrium with endometriosis in the late proliferative phase. However, the activity increased conspicuously in the midsecretory phase, and thus there was no difference in activity in endometrium with or without endometriosis. The observed lowered capacity of glycogen synthesis may lead to understanding the mechanism of infertility associated with endometriosis.

Adult↗

Endometriosis and associated pathology.

The natural history of endometriosis, including the belief that it is a progressive disease, is reviewed with the help of a large, cross-sectional, prospective study and a smaller longitudinal study. Two studies are reviewed that address the role of growth factors in the development of endometriosis. These studies demonstrated that the peritoneal fluid of patients with endometriosis contained significant growth factor activity against human endometrial stromal cells. In a mouse model, macrophage-derived factors stimulated endometrial cell proliferation. The possible correlation between endometriosis and decreased bone mineral density, which was reported by an earlier study, is reviewed. Recent data, however, have shown no correlation between bone mineral density and endometriosis. Finally, several reports on the usefulness of endometrial antibodies and serum CA 125 levels in the diagnosis and treatment of patients with endometriosis are reviewed. These data suggest that both endometrial antibodies and CA 125 measurements may be useful in the diagnosis and treatment of patients with endometriosis.

Adult↗

Prevalence of endometriosis in asymptomatic women.

Numerous studies have identified the presence of endometriosis by its "classic" morphologic characteristics in high-risk patient populations. Recent histologic documentation of "subtle" laparoscopic appearances of this condition suggests that many of the earlier studies may have underestimated its prevalence in the general population. We evaluated the frequency of endometriosis in 86 women who denied having the symptoms typical of the condition and who underwent laparoscopy for other indications (acute pain, sterilization, etc.). Of those patients, 45.3% were found to have definitive evidence of pelvic endometriosis (stage I, 32.5%; II, 9.3%, III, 1.1%; IV, 2.3%). The exclusion of nine patients whose only laparoscopic indication was infertility or tubal occlusion resulted in a 44% finding of endometriosis, while 39% of the patients with documented fertility exhibited endometriosis. Forty-four percent of a subset of asymptomatic women undergoing laparoscopic evaluation prior to vaginal hysterectomy were found to have evidence of endometriosis; all but one had stage I, judged amendable to laser excision. The data suggest that endometriosis may be a more common peritoneal finding in asymptomatic, fertile women than previously believed.

Endometriosis↗

Antigenic differences between the endometrium of women with and without endometriosis.

Serum and peritoneal fluid from 12 women with endometriosis, 4 women with uterine leiomyomata and 6 fertile women without endometriosis (controls) and serum from 4 women with adenomyosis were tested with a passive hemagglutination assay for antibodies against endometrium from all the controls, 8 patients with endometriosis and all patients with uterine leiomyomata and from implants from 8 patients with endometriosis. Serum antibody titers in patients with endometriosis or leiomyomata were significantly higher against endometrial or implant antigens from patients with endometriosis and 2 patients with leiomyomata than those against the controls' endometrium. Peritoneal fluid endometrial antibody titers failed to reflect these antigenic differences. Controls and patients with adenomyosis had low titers of endometrial antibodies in their serum or peritoneal fluid. Antigenic differences appear to exist between the endometrium of patients with endometriosis and that of controls.

Adult↗

Extrapelvic endometriosis presenting as a hernia: clinical reports and review of the literature.

Endometriosis is a common gynecologic diagnosis. Typical complaints of patients with pelvic endometriosis include dysmenorrhea, menstrual irregularities, dyspareunia, and infertility. Endometriosis may also occur in extrapelvic sites and cause unusual symptoms and diagnostic dilemmas. Endometriosis has been described in the inguinal region, and this is illustrated in the first case history. The tender inguinal masses often fluctuate with the menstrual cycle but the condition initially may be confused with an inguinal hernia. Treatment is surgical. Abdominal wall scar endometriosis, seen in the second case, has been described in patients after a wide variety of gynecologic procedures. This also is initially noted as a tender mass, usually fluctuating with menstruation, and is often confused with an incisional hernia. Again, surgery is the treatment of choice. Pathologic features of endometriosis are constant, regardless of location. Microscopically, endometrial glands and stroma, fibrosis, chronic inflammation, and old hemorrhage are seen. Familiarity with the unusual types of endometriosis is important to the general surgeon.

Abdominal Neoplasms↗

Combination medical and surgical therapy for infertile patients with endometriosis.

Endometriosis is a difficult problem for practicing gynecologists and is commonly associated with infertility. The diagnosis of endometriosis should only be made at the time of laparoscopy or laparotomy and should be confirmed with biopsy if possible. Once the diagnosis is made, it should be classified according to the revised AFS system. The treatment of infertility associated with endometriosis is controversial and usually consists of either medical therapy with hormonal manipulation designed to suppress the disease, surgical therapy designed to debulk the disease and repair anatomic distortion, or a combination of both. Despite an abundance of research on the treatment of endometriosis, the pregnancy rate for patients with endometriosis remains lower than that of the normal population. The reasons for this are obscure. Endometriosis does not respond to hormonal changes the same way that normal endometrium does and has been shown to persist despite extensive medical therapy. The recurrence rate of the disease is impressively high after either medical or surgical therapy. Interestingly, expectant management of minimal or mild disease is associated with pregnancy rates equal to those of any other type of therapy. Only when the disease is more extensive does aggressive treatment appear to show improvement in pregnancy rates. Whether combination therapy of endometriosis is better than single agent therapy remains open to debate. Some of the best-designed studies using combination therapy have shown no difference in pregnancy rates. Yet, when taken as a whole, it would appear that if combination medical and surgical therapy is chosen, the medical therapy should be given preoperatively. The literature abounds with a wide variety of classification systems, methods of calculating pregnancy rates, and inclusion of control groups. Because of this disparity between studies, reliable conclusions cannot be drawn.

Combined Modality Therapy↗