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Endometriosis: correlation between histologic and visual findings at laparoscopy.

OBJECTIVE: The purpose of this study was to correlate the diagnosis of endometriosis on the basis of visualization at laparoscopy with the pathologic diagnosis. STUDY DESIGN: A prospective study of 44 patients undergoing laparoscopy for the evaluation of chronic pelvic pain was carried out. All areas suggestive of endometriosis were excised and examined pathologically. Peritoneal biopsy specimens were obtained from areas of normal-appearing peritoneum to rule out microscopic endometriosis. All lesions were identified by anatomic site. Visual and histologic American Fertility Society scores were compared. The positive predictive value, sensitivity, negative predictive value, and specificity were determined for visually identified endometriosis versus the histologic correlate. RESULTS: The mean prevalence of abnormalities visually consistent with endometriosis was 36%, with 18% confirmed histologically. The positive predictive value was 45%; sensitivity, 97%; negative predictive value, 99%; and specificity, 77%; for visual versus histologic diagnosis of endometriosis. Thirty-six percent of the diagnoses were downstaged on the basis of histologic findings. CONCLUSION: A diagnosis of endometriosis should be established only after histologic confirmation.

Adolescent↗

Endometriosis and ovarian cancer: thoughts on shared pathophysiology.

BACKGROUND: Endometriosis appears to predispose to ovarian cancer. How this may occur has been little discussed. STUDY DESIGN: This article reviews the English language literature for in vitro, animal, clinical, and epidemiologic studies linking the two conditions. RESULTS: Pathology case series consistently report endometrioid and clear cell types of ovarian cancer arising from endometriotic foci. Epidemiologic studies have been consistent with this association. There are also marked similarities between the proposed etiology of ovarian cancer and the observed pathophysiology of endometriosis. Specifically, both are characterized by immune alterations. Both conditions are promoted by estrogen excess and by progesterone deficit. Finally, steroid hormones interacting with the immune system may stimulate both endometriosis and ovarian cancer. I propose that the biology common to endometriosis and ovarian cancer represents not just a parallelism, but instead a causal pathway: aberrant immune function, fed by and feeding on estrogens, unbalanced by progesterone, may create a positive feed-forward loop that enhances the growth and invasiveness of endometriosis and promotes its malignant transformation. CONCLUSIONS: The same pathophysiology may orchestrate the progression of endometriosis and its transformation to endometroid and clear cell ovarian neoplasias. This notion of a unifying biology suggests a directed approach to future research and identifies possible chemoprevention strategies for women with endometriosis.

Androgens↗

Gamete intra-fallopian transfer or intrauterine insemination after controlled ovarian hyperstimulation for treatment of infertility due to endometriosis.

We compared the effectiveness of gamete intra-Fallopian transfer (GIFT) and intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) in the treatment of infertility due to endometriosis. This was a retrospective study carried out at a tertiary teaching medical center. A total of 127 consecutive patients with endometriosis were treated with GIFT or IUI after COH between June 1990 and December 1998. Patients were divided into two groups. Group 1 (n = 97) included patients with stages 1 and 2 endometriosis, and group 2 (n = 30) included patients with stages 3 and 4 endometriosis. Laparoscopic conservative surgery for endometriosis was performed prior to IUI for patients in both group 1 and group 2. In group 1, 55 patients underwent 95 cycles of IUI after COH and 42 patients underwent 57 cycles of GIFT. In group 2, 14 patients underwent 16 cycles of IUI after COH, while 16 patients underwent 22 cycles of GIFT. The stimulation protocol for both GIFT and IUI was mid-luteal pituitary down-regulation with a gonadotropin releasing hormone agonist (GnRH-a) followed by gonadotropins. In group 1, the pregnancy rates (GIFT = 50.9%, IUI = 29.4%) and the delivery rates (GIFT = 28.1%, IUI = 14.7%) per cycle were significantly higher in GIFT compared to IUI (p = 0.009 and p = 0.05, respectively). There was no significant differences in the pregnancy rate (GIFT 69%, IUI 50.9%, respectively) or the delivery rate (GIFT 38.1%, IUI 25.5%) per patient. In group 2, there was no significant difference in the pregnancy rate (GIFT 54.5%, IUI 31.3%) or the delivery rate (GIFT 40.9%, IUI 12.5%) per cycle, but the difference in the pregnancy rate (GIFT 75%, IUI 35.7%) and the delivery rate (GIFT 56.3%, IUI 14.3%) per patient was significantly higher in GIFT compared to IUI (p = 0.04 and p = 0.02, respectively). We conclude that, when the same stimulation protocol is used in the early stages of endometriosis, a few cycles of IUI can achieve similar results to GIFT, and therefore should be used first. In advanced stages of endometriosis GIFT appears to be more effective.

Abortion, Spontaneous↗

Vascular endothelial growth factor in the plasma, follicular fluid and granulosa cells of women with endometriosis submitted to in vitro fertilization--a pilot study.

Vascular endothelial growth factor (VEGF), a potent angiogenic factor that is altered in endometriosis, supports the immunological mechanism involved in this disease. The aim of the present study was to assess VEGF concentration in the plasma, follicular fluid (FF) and culture medium (CM) of granulosa cells from patients with endometriosis submitted to in vitro fertilization (IVF). A case-control study was conducted on 14 patients with endometriosis and 14 women without endometriosis submitted to IVF. Peripheral blood samples were collected before and after administration of human chorionic gonadotropin (hCG), in addition to FF and CM samples. Plasma VEGF levels increased after hCG administration in women with endometriosis and in controls, but were significant only in controls. VEGF levels were lower in FF but were significantly increased in the CM of patients with endometriosis. There was no correlation between VEGF and age, response to ovarian stimulation, oocyte or embryo quality, and pregnancy result. The increase of VEGF levels after hCG in both groups demonstrated a positive effect of this hormone on VEGF. VEGF in the FF and CM presented opposite results in endometriosis, suggesting that granulosa cells may show a different behavior in vivo and in vitro.

Adult↗

Exploring the mechanism(s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction.

Several retrospective analyses of our in-vitro fertilization (IVF) and oocyte donation programmes have been carried out in an attempt to gain clinical knowledge of the factors implied in the aetiology of endometriosis-associated infertility. In a first approach, a comparison was made of the IVF outcome between 96 cycles in 78 patients with tubal infertility and 96 more cycles in 59 women with endometriosis. The results indicate that endometriosis patients had a poor IVF outcome in terms of a reduced pregnancy rate per cycle (P < 0.0004), a reduced pregnancy rate per transfer (P < 0.002) and a reduced implantation rate per embryo replaced (P < 0.003). In a second study, we addressed the analysis of patients undergoing oocyte donation. The results showed that patients with this disease have the same chances of implantation and embryo development in vivo as other recipients when the oocytes come from donors without known endometriosis. However, when the results of oocyte donation were classified according to the nature of the oocytes donated, patients who received embryos derived from endometriotic ovaries showed a significantly (P < 0.05) reduced ability to implant compared with the remaining groups. In a third approach, we evaluated embryo development in vitro when women with and without endometriosis underwent IVF and embryo replacement 72 h after oocyte retrieval. We observed a significantly (P < 0.04) reduced number of blastomeres in embryos from endometriosis patients compared with controls, as well as an increased (P < 0.05) incidence of arrested embryos in vitro. Taken together, these observations suggest that infertility in endometriosis patients may be related to alterations within the oocyte which, in turn, result in embryos of lower quality, as demonstrated in our IVF programme, and a lower ability to implant, as shown in the oocyte donation model.

Embryo Implantation↗

The use of biochemical markers in the diagnosis of pelvic endometriosis.

The aim of this study was to evaluate CA 125 II, C-reactive protein (CRP) and serum amyloid A (SAA) and anticardiolipin antibody (aCL) concentrations for the diagnosis of pelvic endometriosis. The study population consisted of 15 women without endometriosis, as confirmed by laparoscopy (group A), and 35 patients with pelvic endometriosis diagnosed by laparoscopy or laparotomy (group B). Group B patients were divided into those at stages I and II of the disease (BI/II) and those at stages III and IV (BIII/IV). Blood samples were obtained twice during the menstrual cycle: on day 1, 2 or 3 of the cycle and on day 8, 9 or 10 of the cycle. CA 125 II and CRP concentrations were higher in group III/IV patients compared with healthy controls, mainly during the first 3 days of the menstrual cycle; SAA concentrations were also higher in this group of patients compared with healthy controls, but only during the first 3 days of the menstrual cycle. Immunoglobulin (Ig) M aCL concentrations were higher in all patients with endometriosis compared with healthy controls, mainly during the first 3 days of the menstrual cycle. It is concluded that these determinations may contribute to the diagnosis and the indication of treatment for pelvic endometriosis. Determination of CA 125 II concentrations at the beginning of the menstrual cycle may aid the diagnosis of stage III and IV endometriosis. IgM aCL appears to be associated with the presence of all stages of the disease, while SAA values are elevated in severe situations. Measurement of these molecules may therefore provide a valuable tool in the diagnosis and management of endometriosis.

Adult↗

Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells.

The peritoneal environment in endometriosis is known to have growth-promoting effects on endometrial cells. To investigate whether follicular fluid, a contributor to the peritoneal fluid, stimulates endometrial cell proliferation, we incubated endometrial stromal cells in culture with various dilutions of follicular fluid obtained from women with or without endometriosis undergoing oocyte retrieval for in-vitro fertilization. Cell proliferation assays were performed using follicular fluid from 28 women (without endometriosis, n = 13; with endometriosis, n = 15) in eight different endometrial stromal cell culture set-ups. Cell proliferation was assessed by a colorimetric method. Maximum cell proliferation was detected when endometrial cells were incubated with 50% dilution of follicular fluid for 48 h. Follicular fluid from women with endometriosis induced significantly higher cell proliferation than follicular fluid from women without endometriosis (P < 0.05). Our findings indicate that follicular fluid contents may contribute to the growth-promoting factors in the peritoneal fluid of women with endometriosis.

Adult↗

Vascular endothelial growth factor (VEGF) in endometriosis.

Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red lesions, suggesting that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions can be considered as the first stage of implantation. After the attachment phase, the high VEGF levels could provoke an increase in the subperitoneal vascular network and facilitate implantation and viability in the retroperitoneal space. Lower VEGF levels in black lesions explain the decrease in both stromal vascularization, followed by fibrosis and inactivation of the implant.

Adult↗

Erythropoietin concentrations are elevated in the peritoneal fluid of women with endometriosis.

Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates the proliferation of early erythroid precursors as well as the differentiation of late erythroid precursors of the erythroid lineage. However, recent studies have indicated that Epo also has angiogenic properties and plays an important role in the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was therefore postulated that Epo may be an important angiogenic factor in endometriosis. In order to address this hypothesis the concentration of Epo in peritoneal fluid (PF) was determined in patients with or without endometriosis. PF was collected from patients with endometriosis (n = 42) or without endometriosis (n = 18). Detectable concentrations of Epo were found in all PF samples analysed. The concentration of Epo in PF from patients with endometriosis was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in patients with endometriosis the Epo concentrations in PF from patients with stage I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml, P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest that Epo may play a role in the pathogenesis of endometriosis particularly in the initiation of the disease.

Adult↗

Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis.

BACKGROUND: The aetiology of endometriosis is unknown. Ectopic dissemination of the endometrial cells gives origin to endometriotic lesions, but occurs in women with and without endometriosis. It has been suggested that increased ectopic cell survival facilitates their implantation. The objectives of this study were to evaluate endometrial apoptosis in women with endometriosis according to: (i) cyclic changes, (ii) glandular and stromal contribution, and (iii) stage of the disease. METHODS: The subjects were women undergoing diagnostic laparoscopy and endometrial biopsies for suspected endometriosis. Spontaneous apoptosis was evaluated using TdT-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Apoptotic cells per 10 mm(2) (apoptotic index) in an area of 10-50 mm(2) in 5 microm endometrial tissue sections were counted and location of these cells was recorded. RESULTS: The apoptotic index in glandular epithelium was lower in endometriosis than controls (26.0 +/- 5.5 versus 51.2 +/- 9.7, P = 0.03) but not in the stroma (36.3 +/- 6.4 versus 48.4 +/- 11.3, NS). In controls, apoptosis was highest during the late secretory/menstrual and early proliferative phases and cyclic variability was apparent. In endometriosis, this cyclic variability was lost. There was a trend toward decreased apoptosis with increasing stage of the disease, but the differences lacked statistical significance. CONCLUSIONS: Spontaneous apoptosis is decreased in the endometrial glands in women with endometriosis, especially during late secretory/menstrual and early proliferative phases of the cycle. This may indicate increased viability of endometrial cells shed during menses, facilitating their ectopic survival and implantation.

Adult↗

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Adolescent↗

Modulation of neutrophil apoptosis by plasma and peritoneal fluid from patients with advanced endometriosis.

BACKGROUND: The increased production of pro-inflammatory chemoattractant cytokines for neutrophils in endometriosis suggests that changes in the immune system play an important role in the pathophysiology of endometriosis. The effects of plasma and peritoneal fluid from patients with advanced endometriosis on the apoptosis of neutrophils were investigated. METHODS: Apoptotic changes of neutrophils were evaluated by morphological changes using Giemsa staining. Apoptosis was confirmed by DNA electrophoretic analysis. RESULTS: Compared with the plasma (n = 20) and peritoneal fluid (n = 5) of healthy controls, the addition of 10% plasma (n = 20) and peritoneal fluid (n = 10) from patients with endometriosis to an in-vitro culture of neutrophils from healthy subjects reduced the percentage of apoptotic cells from 65.3 +/- 6.6 to 27.2 +/- 4.6% (P < 0.001) and from 45.3 +/- 4.8 to 10.5 +/- 4.3% (P < 0.001) respectively. Neutralizing interleukin-8 antibody abrogated the delay of neutrophil apoptosis induced by peritoneal fluid, but not in the plasma of endometriosis patients. CONCLUSIONS: These findings show that interleukin-8 is one of the neutrophil survival factors in the peritoneal fluid of endometriosis patients and that an unidentified survival factor is also present in the plasma of patients with endometriosis.

Adult↗

Insulin-like growth factor (IGF)-1 and IGF binding protein-1 and -3 in the follicular fluid of infertile patients with endometriosis.

BACKGROUND: Endometriosis is associated with pituitary-ovarian axis dysfunction. The study of the follicular fluid in patients with endometriosis is important to elucidate the pathophysiological mechanism of this disease. The objective of this present paper was to analyse the dosages of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 and 3 (IGFBP-1 and IGFBP-3) in the follicular fluid environment of infertile patients with endometriosis. METHODS: A total of 41 infertile patients undergoing IVF between January 1999 and January 2000 participated in the cross-sectional prospective study. Patients were divided into three groups: group I, minimal/mild endometriosis (n = 12); group II, moderate/severe endometriosis (n = 10); and group III, tubal obstruction (n = 19). The ultra-short protocol was used in association with recombinant FSH for ovulation induction. Follicular fluid analysis was performed using radioimmunoassay with specific kits. RESULTS: Follicular fluid IGF-1 and IGFBP-3 levels were not significantly different among the groups; however, follicular fluid IGFBP-1 levels were lower in those patients with moderate/severe endometriosis (P < 0.05). Comparison of ovulation induction time, number of recombinant FSH units, number of follicles, oocytes and embryos, and fertilization and gestation/cycle rates showed non-significant differences. CONCLUSION: Infertile patients with moderate/severe endometriosis, which is associated with ovulatory dysfunction, presented lower levels of IGFBP-1 in the follicular fluid when undergoing IVF.

Adult↗

Mutagen sensitivity as a susceptibility marker for endometriosis.

BACKGROUND: The mutagen sensitivity assay has been well established and widely used as a good independent risk predictor for developing cancers. Although endometriosis is considered a benign disorder, it exhibits several features similar to malignancy. The objectives of this study were to evaluate whether mutagen sensitivity can predict the risk of endometriosis development. METHODS: The subjects were women undergoing different surgical procedures due to different stages of endometriosis. Bleomycin was used as a mutagen, and the mutagen sensitivity of peripheral lymphocytes from women with and without endometriosis was determined by measuring chromatid breaks induced by bleomycin in short-term culture using cytogenetic analysis. RESULTS: The mean +/- SD (range) number of chromatid breaks per cell in women with and without endometriosis was 0.68 +/- 0.12 (0.50-0.94) and 0.52 +/- 0.10 (0.35-0.68), respectively. There was a significant difference with regard to mean chromatid breaks per cell between women with and without endometriosis (P < 0.001). On logistic regression analysis, the odds ratio (95% confidence interval) of chromatid breaks per cell was 5.80 (2.19-15.37, P < 0.001) for cases compared with controls. Yet, variables of interest including age, dysmenorrhoea, previous induced abortion and smoking in the home and workplace were not statistically correlated with chromatid breaks per cell. CONCLUSIONS: These preliminary data suggest that sensitivity to bleomycin-induced chromatid breaks in lymphocytes is associated with the risk of endometriosis development.

Abortion, Induced↗

Nitric oxide synthesis is increased in the endometrial tissue of women with endometriosis.

BACKGROUND: Previous studies have shown that peritoneal macrophages from women with endometriosis produce excess nitric oxide (NO). This study was designed to quantify the amount of NO and determine the expression of endothelial (eNOS) and inducible NO synthases (iNOS) in women with and without endometriosis. METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed on endometrial tissues obtained from controls (myoma, n = 30) and on eutopic/ectopic endometrial tissues from endometriosis patients (n = 34) to evaluate eNOS and iNOS protein concentrations in these endometrial tissues. A rapid-response chemiluminescence analyser was used to measure NO directly in fresh endometrial tissues. RESULTS: Mean (+/- SEM) levels of NO were significantly increased in the endometrial tissues of women with endometriosis (13.2 +/- 7.8 versus 19.8 +/- 12.6 nmol/g tissue; P = 0.016). Apparently higher levels of NO were found in ectopic compared with eutopic endometrium (P = 0.057). Endometrial tissues of women with endometriosis appeared to contain more iNOS than those of controls (3.6 +/- 2.2 versus 8.6 +/- 12.2 pg/ microg protein; P = 0.06), but no significant difference was found in eNOS levels. CONCLUSIONS: Greater amounts of NO and NOS are present in the endometrial tissues of women with endometriosis, implying a possible role for NO in the pathogenesis of endometriosis.

Endometriosis↗

Familial aggregation of endometriosis in a large pedigree of rhesus macaques.

BACKGROUND: Endometriosis occurs in several non-human primate species that have menstrual cycles. This study investigated the prevalence and familial aggregation of endometriosis in one of those species, the rhesus macaque. METHODS: Between 1978 and 2001, 142 animals with endometriosis were identified from necropsy and surgical records and through the use of magnetic resonance imaging (MRI) at the Wisconsin National Primate Research Center, Madison, USA. All cases were used to build one large multigenerational pedigree and nine nuclear families comprising 1602 females in total. By 2002, the pedigrees contained 124 cases diagnosed at necropsy; 17 at surgery and three at MRI. Female animals that had died aged > or = 10 years without endometriosis, had both ovaries until at least 1 year prior to death, and had a full necropsy, were considered unaffected. RESULTS: The prevalence of endometriosis among necropsied animals aged > or = 10 years in the colony was 31.4% [95% confidence interval (CI) 26.9-35.9%]; prevalence increased with rising age and calendar age at death. Familial aggregation of endometriosis was strongly suggested by a significantly higher average kinship coefficient among affecteds compared with unaffecteds (P < 0.001) and a higher recurrence risk for full sibs (0.75; 95% CI 0.45-1.0) compared with maternal half sibs (0.26; 95% CI 0.10-0.41) and paternal half sibs (0.18; 95% CI 0.02-0.34). The segregation ratio among affected mothers (44.2%) was not significantly higher compared with unaffected mothers (36.6%). CONCLUSIONS: The results support familial aggregation of endometriosis in the rhesus macaque, and indicate that this is a promising animal model for the investigation of mode of inheritance, the location of potential genetic susceptibility loci and the influence of environmental factors.

Age Factors↗

The tumor necrosis factor-alpha promoter -1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional proinflammatory cytokine, associated with various inflammatory and autoimmune diseases. Elevated TNF-alpha levels in peritoneal fluid have been reported in women with endometriosis, suggesting that TNF-alpha may be involved in the development of endometriosis. In this study, we investigated the possible association between endometriosis and the TNF-alpha gene promoter polymorphisms -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C in a Japanese population. METHODS: We compared the distribution of the -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C polymorphisms in the promoter region of TNF-alpha in 130 endometriosis cases and 185 controls using PCR-RFLP analysis. RESULTS: The allele frequencies of -238A, -308A, -857T, -863A and -1031C in controls were 2.0%, 1.3%, 19.4%, 17.0% and 18.6%, and in the cases 1.1%, 0.3%, 19.6%, 18.6% and 13.6%, respectively. No significant differences in frequencies were found between the crude endometriosis cases and controls. However, when the endometriosis group was divided into a subgroup of women with stage IV disease only, the frequency of the -1031C allele was significantly lower in this subgroup than controls. CONCLUSIONS: The variability of the -1031T/C polymorphism of the TNF-alpha gene may be associated with susceptibility to (AUTHOR: as meant?) endometriosis.

Asian People↗

Usefulness and limits of CA-125 in diagnosis of endometriosis without associated ovarian endometriomas.

BACKGROUND: The aim of this study was to evaluate the diagnostic significance of CA-125 for endometriosis without ovarian endometriomas. METHODS: Preoperative serum CA-125 levels were measured in 775 consecutive women diagnosed by laparoscopy or laparotomy with endometriosis, adenomyosis, leiomyomas, or normal pelvis. RESULTS: Receiver operating characteristic curve analysis revealed that the area under the curve for endometriosis without endometriomas was 0.788, significantly smaller than that for endometriosis with endometriomas (0.935, P < 0.05). In diagnosis of endometriosis without endometriomas, both the maximal accuracy of 78.8% and the maximal diagnostic value of 61.2% were obtained at the cutoff value of 20 U/mL. Negative predictive value was 78.0% at the cutoff value of 20 U/mL, whereas positive predictive value was 92.9% at the cutoff value of 30 U/mL. This range is clearly superior to the empirical single cutoff of 35 U/mL. CONCLUSIONS: In the diagnosis of endometriosis without endometriomas, combined use of two cutoff values for CA-125, 20 and 30 U/mL, provides improved diagnostic performance. However, the accuracy of using only CA-125 testing for diagnosis is still limited. Serum CA-125 testing can be done during initial screenings of women with possible endometriosis.

Adult↗