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Cytochrome P450c17alpha 5'-untranslated region *T/C polymorphism in endometriosis.

Estrogen plays a role in the pathogenesis of endometriosis. The CYP17 gene codes for the cytochrome P450c17alpha enzyme that is involved in the estrogen biosynthesis. We aimed to investigate if CYP17 polymorphism could be used as marker to predict the susceptibility of endometriosis. Women were divided into two groups: (1) severe endometriosis (n=119); (2) non-endometriosis groups (n=128). A 169-bp fragment encompassing the T/C polymorphic site in 5'-untranslated promoter region (5'-UTR) of the CYP17 was amplified by the polymerase chain reaction, treated with restriction enzyme MspA1I, and electrophoresis. The polymorphism was divided into restriction-enzyme indigestible (T homozygote), T/C heterozygote, and digestible (C homozygote). Genotypes and allelic frequencies for this polymorphism in both groups were compared. We observed a higher but non-significant percentage of T homozygote in the endometriosis women compared with the non-endometriosis women. Proportions of T homozygote / heterozygote / C homozygote for CYP17 in both groups were: (1) 26.1/46.2/27.7% and (2) 17.2/45.3/37.5% (p-value=0.131). T allele was related with higher susceptibility of endometriosis. T and C allele frequencies in both groups were: (1) 49.2/50.8%; (2) 39.8/60.2% (p-value=0.046). Despite the CYP17* T allele appearing to be associated with a trend of increased risk of endometriosis, CYP17 5'-UTR gene polymorphism might not be a useful marker for prediction of endometriosis susceptibility.

5' Untranslated Regions↗

Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis.

INTRODUCTION: As a cytotoxic product of activated monocytes, macrophages, and lymphocytes, tumor necrosis factor alpha (TNF-alpha)--together with other cytokines and growth factors--is an important component in the immune response of the human organism. In addition, TNF-alpha plays a central role in neoangiogenesis. Because of its cytotoxicity with regard to several tumor cells and its motility-hindering effect on human sperm, TNF-alpha is considered to be a significant pelvic mediator of female sterility. OBJECTIVE: The goal of our study was to determine as to whether or not an increased TNF-alpha secretion by peritoneal macrophages (PM) can be measured in female patients with endometriosis compared with healthy subjects, and if TNF-alpha secretion can be correlated with the activity of endometriosis. METHODS: During infertility work-up, 100 female patients underwent a diagnostic laparoscopy. In accordance with the rAFS classification as well as from the macroscopic aspect of the degree of activity of the endometriosis, the patients were divided as follows: an endometriosis-free control group with a completely normal pelvic status (n=35) and three groups with increasing stages of endometriosis (n=65). In the control group (Group 1), the TNF-alpha concentrations (median values with minimum / maximum) were 6.2 pg/ml (1.9/10.2), in Group 2 with rAFS stage I/II less active endometriosis 56.33 pg/ml (39.5/71.2), in Group 3 with rAFS stage I/II but highly active endometriosis 81.41 pg/ml (68.4/98.7), while in Group 4 with rAFS stage III/IV 200,15 pg/ml (182.6/226.8), respectively. CONCLUSION: In conclusion, we were able to show that the TNF-alpha secretion of PM was significantly higher in patients with proven endometriosis compared to the control group. These results were found to be statistically significant and were in accordance with the histological findings. Thus, due to its immunomodulating potential, TNF-alpha may be a marker of both activity and stage of endometriosis.

Adult↗

Functional and phenotypic alterations in peritoneal macrophages from patients with early and advanced endometriosis.

The aim of this study was to elucidate whether peritoneal macrophage (pMO) alterations are a generalized feature in all stages of endometriosis and the effect of hormonal treatment on this leukocyte population. For this purpose we quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+), percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO from patients with early (stages I/II) and advanced (stages III/IV) endometriosis, we also analyzed some of these properties in pMO from patients which had been treated for 6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist (GnRHa). We found that there were a significant increase of the pMO number in both types of patients, though the highest values were obtained in early endometriosis (p < 0.001). Percentages of pMO DR+ were decreased in all patients (p < 0.01) while percentages of pMO NBT+ were significantly increased. Production of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE2 release was not altered in early endometriosis pMO but, in advanced endometriosis, pMO PGE2 levels were 100-fold higher than control values. In posttreatment patients, the number of pMO and percentage of pMO NBT+ were similar to early endometriosis patients, though the percentage of pMO DR+ was within the normal range. We conclude that the pMO population, as well as IL-1 and PGE2 production, were altered in all stages of endometriosis, and that these changes could be involved in the pathogenesis of endometriosis and associated infertility. Hormonal treatments do not reverse the pMO changes.

Adult↗

Polymorphism for transforming growth factor beta 1-509 (TGF-B1-509): association with endometriosis.

Transforming growth factor beta (TGF-B) family members are multi-functional cytokines that play a key role in cellular growth, proliferation, and differentiation. The aim of the study was to investigate whether the TGF-B1-509 gene polymorphism could be used as a marker of susceptibility in endometriosis. Women were divided into two groups: endometriosis (n = 150) and non-endometriosis (n = 159). Polymorphisms for TGF-B 1-509 genes were amplified by polymerase chain reaction and detected after restriction enzyme digestion. Genotypes and allelic frequencies in both groups were compared. Genotype proportions and allele frequencies of TGF-B1 gene polymorphisms differed significantly in both groups. Proportions of C homozygote, heterozygote, and T homozygote for TGF-B1 gene polymorphisms were 9.3/61.3/29.4% in the endometriosis group and 41.3158.510% in the non-endometriosis group. Alleles C and T for TGF-B1 gene polymorphism were 40/60% (endometriosis) and 70.8/29.2% (non-endometriosis). Association of endometriosis with TGF-B 1-509 gene polymorphism exists. T homozygote and T allele for TGF-B1 are associated with higher susceptibility to endometriosis.

Deoxyribonucleases, Type II Site-Specific↗

Sperm phagocytosis by human peritoneal macrophages: a possible cause of infertility in endometriosis.

The mechanism of infertility in women with endometriosis is unknown, but it is independent of mechanical factors that affect fallopian tube function. Increased numbers of peritoneal macrophages are present in women with endometriosis and have access to the female reproductive tract via the oviducts. To determine whether peritoneal macrophages might phagocytize sperm and thereby contribute to infertility in women with endometriosis, we examined peritoneal macrophages from 32 fertile and infertile women; the infertile group was separated into those with and those without visible endometriosis. Peritoneal macrophages from infertile patients with endometriosis phagocytized more normal sperm in vitro (84% +/- 4%) than did those from fertile women (43% +/- 4%) or infertile women without endometriosis (46% +/- 8%) (p less than 0.002). The sperm phagocytosis occurred rapidly and reached a peak by approximately 6 hours. Incubation at 0 degrees C, lysing the macrophages by freezing and thawing, or fixing the macrophages with glutaraldehyde inhibited the sperm uptake by macrophages. The process occurred in cultures with or without serum, thereby indicating that the sperm phagocytosis was not dependent on sperm opsonization with a serum factor. Electron microscopy showed internalization of the spermatozoa into phagosomes with subsequent intravacuolar degradation. These data demonstrate that: (1) peritoneal macrophages phagocytize and degrade sperm in vitro and (2) peritoneal macrophages isolated from women with endometriosis exhibit greater phagocytosis in vitro than do macrophages from fertile women or infertile women without endometriosis. These results suggest that, if peritoneal macrophages from women with endometriosis enter the reproductive tract via the oviducts, they might adversely influence fertilization by phagocytizing sperm.

Adult↗

Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus.

Histologic study of endometriosis and investigation of lymphatic drainage in and out of the uterus were conducted to obtain more information on the histogenesis of endometriosis. Endometriosis is a disease originating from the normal endometrium, specifically from its basal layer. Internal endometriosis (adenomyosis) is caused mainly by direct invasion of the endometrium into the spaces located in the connective tissue of the muscle layer. Serous and ovarian types of endometriosis are frequently found together with adenomyosis. Endometrial fragments in vessels are detected in 4.5% of cases of endometriosis. Observation of serial sections proved that serous endometriosis is caused mainly by continuous or semicontinuous invasion of the tunica muscularis spaces primarily from adenomyosis lesions and partly from the endometrium. Confirmation of lymph flow into the ovary from the uterine body strongly suggests that ovarian endometriosis arises as a consequence of vascular (lymphatic) transport of endometrial fragments from adenomyosis lesions, serous endometriosis lesions, or the endometrium.

Endometriosis↗

Uterine innervation after hysterectomy for chronic pelvic pain with, and without, endometriosis.

OBJECTIVE: Chronic pelvic pain is associated with a wide range of clinical conditions that include endometriosis. The precise cause, mechanisms of pain, and natural history are imprecise. Patterns of uterine innervation have been studied after hysterectomy for chronic pelvic pain with and without endometriosis. STUDY DESIGN: Tissue blocks were taken from the lower one half of the uterus after hysterectomy for advanced endometriosis (n = 16 specimens; group 1) and for chronic pelvic pain without endometriosis (n = 15 specimens; group 2). The control group consisted of uteri that were removed for painless gynecologic conditions (n = 25 specimens; group 3). Tissue sections from the lower one half of the uterus were stained with anti-S100 to demonstrate patterns of innervation, and nerve fiber profiles were counted by standardized techniques; qualitative differences were also recorded. RESULTS: In uteri from women with advanced endometriosis, there were increased numbers of nerve fiber profiles compared with control specimens (group 1 vs group 3; P = .0013, Mann Whitney U test). There were also increased numbers of nerve fiber profiles in uteri that were associated with chronic pelvic pain without endometriosis (group 2 vs group 3; P = .04, Mann Whitney U test). There were no differences in nerve fiber count in uteri from groups 1 and 2 (P = .35, Mann Whitney U test). Comparing both groups of uteri with controls (groups 1 and 2 vs 3) demonstrated marked differences in nerve fiber counts (P = .002, Mann Whitney U test). Two distinctive patterns of reinnervation that were observed: disruption of nerve bundles (collateral sprouting with microneuroma formation) and ingrowth around blood vessels (perivascular nerve fiber proliferation). There were increased numbers of microneuromas (groups 1 and 2 vs 3; P = .001, chi-squared test with Yates correction) and perivascular nerve fiber proliferation (groups 1 and 2 vs 3; P = .008, chi-squared test with Yates correction) in the myometrium in chronic pelvic pain with, and without, endometriosis compared with the control group. CONCLUSION: Nerve fiber proliferation and other features of reinnervation have been observed in the isthmic regions of uteri that were removed at hysterectomy for chronic pelvic pain with and without endometriosis. There were no quantitative differences between the groups with chronic pelvic pain and endometriosis. These observations provide an alternative explanation for the source of pain and other clinical symptoms in these clinical settings.

Adult↗

Pathogenesis of endometriosis.

Many women harbour spots of peritoneal endometriosis without having any symptoms; this is referred to as the phenomenon endometriosis. Some of these women go on to develop symptomatic endometriosis. Although we know the factors potentially involved in the aetiology and pathogenesis of endometriosis, the exact mechanism by which the phenomenon endometriosis develops into the disease endometriosis, with its associated signs and symptoms, remain obscure. The widely accepted theory is Sampson's transplantation theory. Recent findings indicate that certain properties of the endometrium, and the influence of the local environment, are crucial in the development of endometriosis. Early endometriosis lesion formation is described in detail, as this seems to be a key process in the development of peritoneal endometriosis.

Endometriosis↗

Apoptosis pattern in human endometrium in women with pelvic endometriosis.

OBJECTIVE: In the present study we aimed to describe apoptosis patterns in eutopic endometrium in women suffering from endometriosis in order to assess its value as a marker of early forms of endometriosis, and also to try to answer whether endometriosis is caused by changes within the eutopic endometrium or whether endometriotic lesions change the characteristics of eutopic endometrium. STUDY DESIGN: The study was performed on 125 women treated in Division of Reproduction. In 52 patients peritoneal endometriosis was diagnosed (I(0)-23; II(0)-29). Seventy-three patients in whom no endometriotic foci could be found at laparoscopy were qualified as the control group. Endometrial biopsy 7-9 days after ovulation was taken for assessment of apoptosis (TUNEL) and routine histology. RESULTS: Apoptosis indices in the eutopic endometrium of women with endometriosis were lower compared to women without endometriosis. In the endometrial glands apoptosis indices were 2.94+/-1.66 versus 5.23+/-2.06 (p<0.01) in the group of women with and without endometriosis, respectively. In the endometrial stroma apoptosis indices were estimated at 2.04+/-1.72 in women with endometriosis and 4.12+/-1.62 in the control group (p<0.01). CONCLUSIONS: The observed changes could support the hypothesis of the different properties of eutopic endometrium in endometriotic women as a causing factor of peritoneal endometriosis.

Adult↗

Endometrioid adenocarcinoma of the ovary and endometriosis.

OBJECTIVE: We present a retrospective analysis of 22 cases of endometrioid ovarian carcinoma, reviewed to identify endometriosis and its malignant transformation. STUDY DESIGN: Twenty-two patients with endometrioid ovarian cancer were included in the review. Their clinical and histological data were retrospectively reviewed. The origin of the tumours was considered endometriosis-related when the presence of malignant changes in endometriosis glands leading to endometrioid carcinoma were found. RESULTS: Endometriosis was detected in three cases (3/22=14%). One of them presented a clearly benign to malignant transformation area. In another patient, the transition zone was abrupt and present in both ovaries. In the third, a pre-menopausal woman, ovarian endometriosis with only focal endometrioid carcinoma was observed. The three of them had a clear-cell carcinoma component. The presence of a clear-cell component was significantly greater in patients with endometriosis than in patients without endometriosis Each patient had a different clinical presentation: increase in abdominal perimeter, post-menopausal vaginal haemorrhage and hypermenorrhea. Preoperative CA 125 levels were avalaible in 15 of the patients (15/22=68%). Endometriosis was found in two of these 15 patients, both with the highest CA 125 measured levels, exceeding 1700 U/ml. In the remaining of the patients, CA 125 value did not exceed 35 U/ml. CONCLUSION: Although this association is not very frequent, patients with ovarian endometriosis and a high CA 125 serum level should be managed with special care, regardless of their pre-menopausal or post-menopausal status.

Adenocarcinoma, Clear Cell↗

Clinical aspects and surgical treatment of urinary tract endometriosis: our experience with 31 cases.

OBJECTIVES: To present and discuss clinical and surgical management of urologic endometriosis. METHODS: Retrospective review of a database on surgical patients with endometriosis. RESULTS: Thirty-one patients (incidence, 2.6%; mean age, 33.1 yr) were affected by urologic endometriosis (bladder, 12; ureter, 15; both, 4). Bladder endometriosis was revealed by symptoms related to menses and showed a typical endoscopic picture, whereas ureteral involvement had a nonspecific or silent symptomatology. All patients affected by bladder endometriosis and undergoing transurethral resection (2 cases) developed a bladder recurrence; a ureteral recurrence was observed in two of six patients submitted to laparoscopic ureterolysis and in one of two patients submitted to ureterectomy with ureteroureterostomy. Conversely, no relapses were observed among the 14 patients who had partial cystectomy or the 9 who had ureterectomy and ureterocystoneostomy. Finally, two patients underwent nephrectomy due to end-stage renal atrophy. CONCLUSIONS: Cystoscopy is advisable in women with pelvic endometriosis with lower urinary tract symptoms; the upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement. Partial cystectomy gives the best results when used to treat bladder endometriosis. Ureterolysis can be successful only in case of limited ureteral involvement with no urinary obstruction, whereas terminal ureterectomy and ureterocystoneostomy should be preferred in case of obstructive ureteral endometriosis.

Adult↗

Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis.

OBJECTIVE: To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women with endometriosis when compared with women without the disease during menstrual and luteal phases of the cycle. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University hospital. PATIENT(S): A total of 35 patients (20 patients during the luteal phase and 15 patients during the menstrual phase) were selected for this study on the basis of cycle phase and presence or absence of endometriosis. INTERVENTION(S): In this study, endometriosis was laparoscopically and histologically confirmed in 24 women with endometriosis of revised American Society for Reproductive Medicine (ASRM) stage I-II (n = 12) and revised ASRM stage III-IV (n = 12), and the presence of a normal pelvis was documented by laparoscopy in 11 control patients. The macroscopically normal peritoneum tissues were collected from lateral wall left or right, near the colon ascendens or descendens. MAIN OUTCOME MEASURE(S): The expression levels were determined as ratios between the target molecules and beta-actin as housekeeping gene. RESULT(S): In women with endometriosis, peritoneal mRNA levels of matrix metalloproteinase (MMP)-3, transforming growth factor-beta, interleukin (IL)-6, and intercellular adhesion molecule-1 and endometrial mRNA levels of MMP-3, tumor necrosis factor (TNF)-alpha, and IL-8 were significantly higher during the menstrual phase when compared with luteal phase. During the menstrual phase of the cycle, both endometrial expression of TNF-alpha, IL-8, and MMP-3 mRNA levels and peritoneal expression of transforming growth factor-beta, IL-6, and intercellular adhesion molecule-1 mRNA levels were significantly higher in women with endometriosis when compared with controls. Immunohistochemical staining confirmed the presence of TNF-alpha in peritoneum and endometrium in both women with endometriosis and controls. CONCLUSION(S): Increased endometrial and peritoneal cytokine mRNA expression during menstruation may contribute to a pelvic inflammatory microenvironment favoring the development of endometriosis.

Biomarkers↗

Differential expression of genes in eutopic and ectopic endometrium from patients with ovarian endometriosis.

OBJECTIVE: To investigate whether genes that had been found to be differentially expressed in deep-infiltrating endometriosis and matched eutopic endometrium in our previous complementary DNA microarray study also are differentially expressed in ovarian endometriosis and matched eutopic endometrium. DESIGN: Prospective study. SETTING: University hospital in France. PATIENT(S): Patients with ovarian endometriosis. INTERVENTION(S): During surgery, paired samples of tissue representing ovarian endometriosis and eutopic endometrium were obtained from 12 patients. MAIN OUTCOME MEASURE(S): Expression levels of messenger RNA for heat shock protein 90 alpha (HSP90A), chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2), prostaglandin E(2) receptor subtype EP3 (PGE(2)EP3), tyrosine kinase receptor B (TrKB), and 17beta-hydroxysteroid dehydrogenase type 2 (17betaHSD2; epithelial cells) and of platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta 1 (PKCbeta1), Janus kinase 1 (JAK1), mitogen-activated protein kinase kinase (MKK7), Sprouty2, mu-opioid receptor (MOR), and 5HTT (stromal cells) from ovarian endometriosis and matched eutopic endometrium were determined by using laser capture microdissection and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques. RESULT(S): Expression of PDGFRA, PKCbeta1, JAK1, HSP90A, COUP-TF2, MOR, and 17betaHSD2 was significantly higher in ovarian endometriosis than in eutopic endometrium, whereas that of Sprouty2 and PGE(2)EP3 was significantly lower. There was no significant difference in mitochondrial RNA expression of MKK 7, TrKB, and 5HTT. CONCLUSION(S): Ovarian endometriosis might share several common molecules with deep-infiltrating endometriosis that act to sustain endometriotic lesions, whereas molecules involved in local endocrine control might be different between these two types of endometriosis.

Endometriosis↗

Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis.

OBJECTIVE: To detect and quantify mast cells in peritoneal, ovarian, and deep infiltrating endometriosis and to study the relationship between mast cells and nerves in endometriosis. DESIGN: Prospective histological and immunohistochemical study. SETTING: University of Brussels, Belgium. PATIENT(S): Sixty-nine women undergoing laparoscopic excision of endometriosis for pain. Thirty-seven biopsies of normal tissue were obtained from women without endometriosis. INTERVENTION(S): Excision of endometriosis from different anatomical locations. MAIN OUTCOME MEASURE(S): Immunohistochemistry with chymase and tryptase to confirm the presence of mast cells and activated mast cells, respectively, in endometriotic lesions. Quantification of mast cells, activated mast cells, and degranulating mast cells in the different locations of endometriosis. Study of the relationship between mast cells and nerves by quantifying mast cells located less than 25 mum from nerves immunohistochemically stained with S-100 protein. Preoperative pain score evaluation by visual analogue scales. RESULT(S): Patients with deeply infiltrating lesions had significantly higher preoperative pain scores than patients with peritoneal or ovarian endometriosis. Mast cells and degranulating mast cells are significantly more abundant in endometriotic lesions than in nonaffected tissues. Deep infiltrating lesions show a significantly higher number of mast cells, activated mast cells, and mast cells located <25 microm from nerves than peritoneal and ovarian lesions. We found significantly more degranulating mast cells in deep infiltrating lesions than in peritoneal lesions. CONCLUSION(S): The presence of increased activated and degranulating mast cells in deeply infiltrating endometriosis, which are the most painful lesions, and the close histological relationship between mast cells and nerves strongly suggest that mast cells could contribute to the development of pain and hyperalgesia in endometriosis, possibly by a direct effect on nerve structures.

Adult↗

Quantitative expression of apoptosis-regulating genes in endometrium from women with and without endometriosis.

OBJECTIVE: To quantitate antiapoptotic and proapoptotic gene expression in endometrial cells (ECs) of women with and without endometriosis. DESIGN: Determination of transcript abundance (TA) of apoptosis-regulating genes in eutopic and ectopic endometrial cells. SETTING: Institute for the Study and Treatment of Endometriosis, Chicago, Illinois, and university-based research laboratories. PATIENT(S): Women with (n = 10) and without (n = 6) endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative virtually multiplexed transcript abundance measurement (VMTA) of the BCL2, BCLxL, defender against cell death-1 (DAD-1), BCLxS, P53, Caspase-1, and proliferating cell nuclear antigen (PCNA) genes. RESULT(S): The TA ratio of antiapoptotic to proapoptotic isoforms of the BCL-X gene favors survival in eutopic and ectopic ECs from women with endometriosis, but not control ECs. This was found throughout the menstrual cycle for ectopic ECs. Eutopic but not ectopic ECs also expressed increased TA of the antiapoptotic DAD-1 gene in endometriosis. Eutopic and ectopic ECs from women with endometriosis expressed decreased TA of p53 and Caspase-1 compared to ECs from women without endometriosis. Expression of these genes was not correlated with the proliferative state of ECs based on TA of the PCNA gene. CONCLUSION(S): Dysregulation in expression of pro- and antiapoptotic regulatory genes characterizes eutopic and ectopic ECs from women with endometriosis. These results are consistent with apoptotic resistance and enhanced survival of ECs in endometriosis.

Adult↗

Altered expression of interleukin-18 in the ectopic and eutopic endometrium of women with endometriosis.

OBJECTIVE: This study has investigated the expression of interleukin (IL)-18 in the eutopic and ectopic endometrium of women with endometriosis and the role of IL-18 on the pathogenesis of endometriosis. METHODS: Endometriotic tissue specimens and endometrium specimens were obtained from patients with endometriosis. IL-18 protein was determined by immunohistochemical analysis. Expression levels of IL-18 mRNA were analyzed by reverse transcriptase (RT)-PCR. RESULTS: IL-18 was detected in the glandular epithelial and stromal cells of eutopic and ectopic endometrium. RT-PCR analysis showed that endometrial IL-18 mRNA expression levels were significantly higher at the secretory phase than the proliferative phase in normal women, but not in patients with endometriosis. IL-18 mRNA expression levels were lower in the ectopic endometrium than in the eutopic endometrium of women with endometriosis. IL-18 mRNA levels in both ectopic and eutopic endometrium of patients with endometriosis were lower than in endometrium of women without endometriosis. CONCLUSION: Ectopic and eutopic endometrial IL-18 was down-regulated in women with endometriosis, suggesting that IL-18 might play a pathogenic role in the formation of endometriosis.

Adult↗

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP-3 protease activity in the peritoneal fluid of patients with and without endometriosis.

OBJECTIVE: To compare levels of insulin-like growth factor (IGF) components in the peritoneal fluid of patients with and without endometriosis. DESIGN: Patients with endometriosis were compared with control patients. SETTING: Seoul National University Hospital, Korea. PATIENT(S): Forty-three patients with endometriosis and 20 patients without endometriosis. INTERVENTION(S): Peritoneal fluid specimens were collected. MAIN OUTCOME MEASURE(S): Insulin-like growth factors, IGF binding protein (IGFBP) profiles and IGFBP-3 protease activity. RESULT(S): The IGF-I levels in peritoneal fluid were significantly higher in patients with endometriosis than in control patients, while the IGFBP-3 levels and the relative proportion of IGFBP-2 in peritoneal fluid were significantly lower in patients with endometriosis than in control patients. However, IGF-II levels, IGFBP-4 profiles, and IGFBP-3 protease activity did not differ significantly between the two groups. No correlation between these IGF components in peritoneal fluid and the stage of endometriosis was noted. CONCLUSION(S): The profiles of IGF components in peritoneal fluid of patients with pelvic endometriosis may play an important role in the growth of ectopic endometrium and endometriosis-induced infertility.

Adult↗

Atypical endometriosis revisited: clinical and biochemical evaluation of the different forms of superficial implants.

OBJECTIVE: To investigate the activity of different forms of endometriosis implants by clinical and biochemical evaluation. DESIGN: Prospective, blinded study. SETTING: Tertiary-care university hospital. PATIENT(S): Forty-seven infertile patients with minimal or mild endometriosis diagnosed at laparoscopy were included in the clinical investigation. INTERVENTION(S): Patients were submitted to a preoperative evaluation of endometriosis-associated dysmenorrhea by means of a 10-point linear analog scale and to laparoscopic staging of endometriosis following a current classification system. In the biochemical investigation, tissue samples from different endometriosis lesions and control tissues were assessed for prostaglandin (PG) F(2 alpha) production. MAIN OUTCOME MEASURE(S): Evaluation of the correlation between endometriosis-associated dysmenorrhea and the extent of the disease. Evaluation of the production of PGF(2 alpha) by the different tissues sampled. RESULT(S): No positive correlation was present between any of the implant subgroups and the associated dysmenorrhea. White peritoneal implants were associated with milder pain symptoms than black or red lesions. The biologic activity of red and black superficial implants, expressed as the production of PGF(2 alpha), was similar. CONCLUSION(S): No positive correlation was demonstrated between endometriosis-associated dysmenorrhea and the current classification of endometriosis, which includes characterization of the different morphologic aspects of superficial endometriosis implants.

Adult↗