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Objective: To establish the prevalence of endometriosis metastatic to pelvic sentinel lymph nodes (PSLN) in women with ovarian and/or peritoneal endometriosis., Design: Prospective clinical study., Setting: Academic research institution., Patient(s): Women with a laparoscopic diagnosis of ovarian and/or peritoneal endometriosis verified by intraoperative frozen section analysis., Intervention(s): Resection of endometriotic lesions and PSLN after cervical blue dye injection., Main Outcome Measure(s): Histologic analysis of PSLN for the presence of endometriosis and immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK), and CD-10 expression., Result(s): The study enrolled 26 women with suspected endometriosis; endometriosis was confirmed in 23 women, and a PSLN was identified in 19 women. A total of 37 (right side: 20; left side: 17) lymph nodes were removed. The prevalence of endometriotic lesions in PSLN was 11% (2 of 19). Both lesions were positive for ER, PR, CK, and CD-10. Isolated endometriotic-like cells (IELCs) staining positive for ER and PR were identified in the peripheral sinus of 16 (80%) of 20 and 14 (70%) of 20 PSLN, respectively. All IELCs lacked CK staining, whereas CD-10 staining was present in 16 (80%) of 20 cases, indicating a stromal origin of IELCs. Intraoperative and/or postoperative complications were observed in 1 (5%) of 19 women., Conclusion(s): Spread of IELCs to PSLN is common in ovarian and/or peritoneal endometriosis. Metastatic lesions in PSLN are present in 11% of women. Further studies to evaluate the prognostic and predictive value of endometriotic spread to PSLN are warranted., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Initial publications examining the hereditary aspects of endometriosis appeared in the early seventies and demonstrated an up to seven-fold risk for endometriosis in first-degree relatives of endometriosis patients. The aim was to evaluate the influence of hereditary aspects on the endometriosis risk in our patient collective., Methods: In a retrospective cohort study we evaluated the incidence of endometriosis among first-, second-, and third-degree relatives of endometriosis patients and compare it with its incidence among first-, second-, and third-degree relatives of patients without endometriosis., Result(s): Eighty patients in whom endometriosis had been confirmed laparoscopically and histologically by biopsy and 60 patients in whom no endometriosis had been found during laparoscopy were given a questionnaire about the presence of symptoms associated with endometriosis and its family incidence. Patients of both the endometriosis and the control group were 37.7 +/- 6.2 and 45.9 +/- 12.0 years of age at the time of the interview, respectively (p < 0.05). Information about the presence of endometriosis was more readily available for relatives of those in the endometriosis group than for those in the control group (325/749 [43.4%] vs. 239/425 [56.2%], p < 0.05). In 5/136 (3.7%) and 8/134 (6.0%) first-degree relatives of endometriosis patients and the control group, respectively, information about the presence of endometriosis was not available (p = 0.554). Endometriosis was found in 8/136 (5.9%) first-degree relatives of patients and in 4/134 (3.0%) first-degree relatives of controls in the real-case analysis (p = 0.248). When comparing endometriosis characteristics between endometriosis patients with and without a history of familial endometriosis, no significant differences were found., Conclusion(s): There is a trend toward an increased familial incidence of endometriosis. In contrast to the literature, we found a less dramatic increase in familial risk for the development of endometriosis.

Background: Implanon has been reported to be effective in the treatment of dysmenorrhea. We compared the therapeutic efficacies of depot medroxyprogesterone acetate (DMPA) and Implanon with regard to pain relief in women with endometriosis., Study Design: In a clinical research center at a university hospital, 41 patients with dysmenorrhea, nonmenstrual pelvic pain and dyspareunia associated with histologically proven endometriosis were included in an open, prospective, randomized, controlled clinical trial. Twenty-one women were assigned by computer-generated randomization to receive Implanon, and 20 women to receive DMPA. As main outcome measures of this pilot study, we evaluated pain improvement quantified according to visual analog scale score, side effects, vaginal bleeding patterns, withdrawal rate and overall degree of satisfaction., Results: During a follow-up period of 1 year, we ascertained a clear improvement in pain intensity for both treatment options. After 6 months, the average decrease in pain was 68% in the Implanon group and 53% in the DMPA group. The side-effects profile and the overall degree of satisfaction after study termination were comparable for both treatment options., Conclusion: Concerning pain relief, the therapeutic efficacy of the contraceptive implant Implanon is not inferior to that of DMPA in symptomatic endometriosis.

Objective: To investigate alterations in the overall gene expression profile of endometriosis-derived stroma with increasing concentrations of hCG by using the Affymetrix GeneChip U133 Set., Design: In vitro study., Setting: Academic research institution., Patient(s): Women undergoing diagnostic laparoscopic surgery for endometriosis., Intervention(s): Increasing concentrations of hCG, added to fibroblast monocultures from endometriotic lesions., Result(s): We have found that hCG concentrations of 0.1 U/mL and higher lead to a dose-dependent increase in the expression of 68 genes. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix (ECM) remodeling, apoptosis, and inflammation. We then incubated stromal monocultures from nine patients treated with and without 50 U/mL of hCG and performed reverse transcriptase-polymerase chain reaction (RT-PCR) for selected, highly up-regulated genes to validate our DNA array findings and to confirm that the alterations in the gene expression signature are exemplary of patients with endometriosis., Conclusion(s): We have shown that hCG induces dose-dependent alterations in the gene expression profile of stromal cells obtained from endometriotic lesions and have, for the first time, identified potential mechanisms by which hCG might exert its therapeutic effect on endometriotic lesions.

Objective: Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model., Methods: In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solid-phase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha IVS1 -401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models., Results: In a univariate model, HSD17 vlV A->C was associated with a significantly increased risk of endometriosis (P = .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also significantly associated with endometriosis (P = .002)., Conclusion: We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic marker of endometriosis., Level of Evidence: II-2.

Background: Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. This condition causes painful periods, chronic pelvic pain, subfertility and a profound reduction in quality of life, especially during women's reproductive years. Currently available medical therapies offer comparatively little therapeutic benefit and are often burdened by considerable side effects. However, since clinical evidence shows that pregnancy leads to alleviation of endometriotic symptoms, we have for the first time examined the effect of human chorionic gonadotrophin (HCG) injections on symptoms such as dysmenorrhea and pelvic pain., Patients and Methods: Thirty-one patients with histologically verified endometriosis refractory to therapy received 1 to 2 intramuscular injections of 1500 to 5000 IU HCG per week for a period of 3-12 months. A QoL questionnaire and the visual analog pain intensity scale (VAS) were used to evaluate quality of life and pain intensity, respectively, before and after three months of treatment., Results: Three months of HCG therapy led to a highly significant reduction of endometriosis-related pain (p<0.001, Wilcoxon test) and to improvement of disease-related parameters such as sleeplessness (p<0.001), irritability (p<0.001), overall discomfort (p<0.001), depressive moods (p<0.001) and painful defecation (p=0.01). Dyspareunia and dysmenorrhea also clearly improved (both p<0.001), though HCG did not lead to significant reduction of dysuria (p=0.66). Prolonged therapy with HCG for up to 12 months (mean: 4.42 months) did not lead to reduction of the beneficial effect., Conclusions: HCG injections lead to significant and clinically relevant reduction in pain intensity and to greatly improved quality of life in women with therapy-refractory endometriosis. The remarkable clinical effect of parenteral HCG in our study will have to be confirmed in additional trials but clearly indicates an extremely promising new perspective in the treatment of endometriosis.

Endometriosis is a multifactorial disease affecting up to 15% of women of reproductive age. This condition is characterized by the presence and growth of endometrial cells outside the uterus. Susceptibility to endometriosis depends on complex interactions of immunologic, hormonal, environmental and genetic factors. Although familial inheritance plays a role, multiple candidate genes appear to be involved. New studies investigating the influence of genetic variants on endometriosis are published with increasing frequency. A number of technologies have emerged to facilitate progress in this field, including subtractive cDNA hybridization to identify secretory endometrial genes, DNA chip technology, differential display polymerase chain reaction, cytogenetics evaluation of endometriotic cells and tissues, and complementary methods in proteomics and informatics. One general approach to uncovering genes pivotal to endometriosis is to search systematically for perturbations in selective candidate genes or chromosomal regions using polymerase chain reaction. We describe here novel association studies on obvious candidates, including genes governing cancer susceptibility, hormone sensitivity or immunology. The assessment of mutations and polymorphisms may allow individualization of therapies as well as primary and secondary prevention strategies for endometriosis, aimed at high-risk populations.

Objective: Experimental data indicate that interleukin (IL)-1 plays a role in the pathogenesis of endometriosis. We determined the genotype and the allele frequencies of the IL1B exon 5 polymorphism and the corresponding IL-1beta serum levels in women with endometriosis., Methods: We genotyped 92 women with surgically and histologically confirmed endometriosis and 69 controls without history of endometriosis. Both groups were of middle European genetic background for the IL1B exon 5 polymorphism (at position +3954). Genotyping was performed by pyrosequencing. IL-1beta serum levels were analyzed by a commercially available enzyme-linked immunosorbent assay., Results: Allele frequencies in women with endometriosis and controls were 76.6% and 76.8%, respectively, for the E1 allele (wild type) and 23.4% and 23.2%, respectively, for the E2 allele (polymorphic) (odds ratio 1.01; P > .99). The investigated polymorphism of the IL-1beta gene was not correlated with IL-1beta serum levels., Conclusions: We did not find an association between the IL1B exon 5 polymorphism, endometriosis, or increased serum IL-1beta levels.

Interleukin (IL)-6 has been implicated in the etiology of endometriosis. A single nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter appears to influence IL-6 transcription rates in vitro and basal IL-6 levels in vivo. We determined the genotype and the allele frequencies of the -174 IL-6 promoter polymorphism and the corresponding IL-6 serum levels in women with endometriosis. The pyrosequencing technique was used to assess the IL-6 genotypes in 94 women with histologically confirmed endometriosis (study group). A series of 70 healthy women without history of uterine disease served as clinical controls (control group).Allele frequencies for the G allele among women with and without endometriosis were 59.6% and 55.0%, respectively (P =.430; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.53, 1.29). Homozygotes for the protective allele C were present in 17.0% of women with endometriosis and in 18.6% of controls were homozygous for the protective allele C (P =.797; OR 0.90, 95% CI 0.40, 2.02). When patients with various disease manifestations were compared, we found an association between the -174 G allele and chocolate cysts (P =.037). Serum levels of IL-6 were significantly higher in women with endometriosis than in controls (P <.001), with highest levels in women with chocolate cysts. There was no association between serum IL-6 levels and IL-6 genotype. The IL-6 promoter polymorphism -174 G/C does not contribute significantly to overall disease susceptibility but does predispose the carrier to distinct endometriosis with chocolate cysts. A genetically determined high IL-6 response might play a pathogenic role in this disease condition.

To explore whether having the mutant tumor necrosis factor (TNF)2 (G-308*A) and TNFA-A (G-238*A) alleles in the TNF-alpha gene promotor region is higher in women with endometriosis, we determined the respective genotype and allele frequencies in a retrospective case-control study. Polymerase chain reaction was performed to identify the G-308A and G-238A promotor polymorphisms in 92 women with surgically and histologically confirmed endometriosis. A series of 69 healthy women without a history of endometriosis served as clinical controls. The allele frequencies of the TNF2 polymorphism were 0.13 and 0.16 in women with endometriosis and in the control group, respectively, and the frequencies of the TNFA-A polymorphisms in women with endometriosis and in the control group were 0.04 and 0.05, respectively, with no significant difference between the study and control groups. The TNF2 polymorphism was present in the homozygous form (TNF(2/2)) in 4.3% of women with endometriosis and in 2.9% of controls (P=.7). No TNFA-A homozygotes (TNFA(A/A)) were detected. We studied TNF-alpha promotor gene variants among women with endometriosis and found that having the G-308A TNF-alpha and the G-238A TNF-alpha polymorphism was not associated with endometriosis in a white population.

Purpose: Catechol-O-methyltransferase (COMT) inactivates the estradiol metabolites, 2-hydroxy and 4-hydroxy catechols, which have been implicated in the pathogenesis of endometriosis. A COMT valine to methionine polymorphism (G-to-A) in exon 4 of the COMT gene is polymorphic in the human population, with 25% of Caucasians being homozygous for the low-activity allele (COMT-L) of the enzyme. In a case-control study we investigated whether this COMT polymorphism is associated with endometriosis., Methods: Polymerase chain reaction was performed to analyze the COMT genotype among women with surgically and histologically confirmed endometriosis (study group; n = 91) and in women without evidence of endometriosis confirmed by laparoscopy or laparotomy (control group; n = 92)., Results: Allele frequencies for the low-activity allele (COMT-L) among women with endometriosis and controls were 0.50 and 0.50, respectively (p = 0.999; odds ratio = 1.0, 95% CI: 0.66-1.51)., Conclusions: Our results suggest that the valine to methionine polymorphism in exon 4 of the COMT gene is not associated with the risk of endometriosis compared to a surgical control population.

Objective: To investigate the association between the 306-base pair insertion polymorphism in intron G of the progesterone receptor (PROGINS) and endometriosis., Design: Case-control study., Setting: Tertiary care center., Patient(s): Ninety-five white women with surgically diagnosed and histologically confirmed endometriosis and 107 white women without endometriosis (controls)., Intervention(s): Determination of PROGINS was performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and distribution of the PROGINS allele., Result(s): Frequencies of the mutant allele T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio, 2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women with endometriosis and 0.9% of controls., Conclusion(s): PROGINS appears to be associated with endometriosis in white persons.

Background: To compare laparoscopic-assisted vaginal hysterectomy (LAVH) with and without bipolar vessel sealing (BVS) using the LigaSure™ device by meanings of intra- and postoperative course. Methods: In a retrospective case-control study 362 female patients (mean age 54.3 ± 9.5 years) were included who underwent LAVH with ( n = 252) and without ( n = 110) use of BVS. Intra- and postoperative courses and adverse events were evaluated. Results: A shorter mean operating time was found for LAVH with the use of BVS (65.28 ± 16.33 min) when compared with LAVH without the use of BVS (83.73 ± 21.53 min, P < 0.005). The mean postoperative stay did not differ significantly between the two groups ( P > 0.05); 15 out of 251 (6.0%) patients were found to have adverse events during or after LAVH with the use of BVS in contrast to 16 out of 110 (14.5%) patients during or after LAVH without the use of BVS ( P < 0.05). Following the use of BVS significantly less patients reported postoperative pain for more than 7 days after the operation in contrast to the use of sutures (0/251 [0%] vs. 3/110 [2.7%], respectively, P < 0.05). Conclusion: The use of LigaSure™ is effective in decreasing operating time, the overall complication rate and postoperative pain. [ABSTRACT FROM AUTHOR]

Objective: Experimental data indicate that interleukin (IL)-1 plays a role in the pathogenesis of endometriosis. We determined the genotype and the allele frequencies of the IL1B exon 5 polymorphism and the corresponding IL-1β serum levels in women with endometriosis. Methods: We genotyped 92 women with surgically and histologically confirmed endometriosis and 69 controls without history of endometriosis. Both groups were of middle Euroepan genetic background for the IL1B exon 5 polymorphism (at position +3954). Genotyping was performed by pyrosequencing. IL-1β serum levels were anlayzed by a commercially available enzyme-linked immunosorbent assay. Results: Allele frequencies in women with endometriosis and control swere 76.6% and 76.8%, respectively, for the E1 allele (wild type) and 23.4% and 23.2%, respectively, for the E2 allele (polymorphic) (odds ratio 1.01; P >.99). The investigated polymorphism of the IL-1β gene was not correlated with IL-1β serum levels. Conclusion: We did not find an association between the IL1B exon 5 polymorphism, endometriosis, or increased serum IL-1η levels. [ABSTRACT FROM AUTHOR]

Examines the relationship between catechol-o-methyltransferase and endometriosis. Factors contributing to the multifactorial etiology of endometriosis; Causes of the growth of ectopic endometrial cells; Role of environmental toxins in the etiology of endometriosis.

Preliminary studies have shown that systemic β-human chorionic gonadotrophin (βHCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism, however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of βHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that βHCG concentrations of 0.1 U/ml and higher Lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a duster analysis which identified three dusters of genes with a comparable expression pattern in response to increasing concentrations of βHCG. Most of the upregulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation. Stromal monocultures from eight patients, treated with and without 50 U/ml of βHCG, were then incubated and real-time polymerase chain reaction for the highly up-regulated genes PAI2, DUSP6, PLAU and MMP1 performed in order to validate the cDNA array findings in patients with endometriosis. Taken together, this study shows that βHCG induces dose-dependent characteristic response clusters in the gene expression profile of stromal cells obtained from endometriotic lesions which could explain the differential biological responses of βHCG in endometriosis. [ABSTRACT FROM AUTHOR]