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PubMed2006

Expression of the proto-oncoprotein breast cancer nuclear receptor auxiliary factor (Brx) is altered in eutopic endometrium of women with endometriosis.

OBJECTIVE: To evaluate the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), and breast cancer nuclear receptor auxiliary factor (Brx) in eutopic endometrium of normal women and women with endometriosis. DESIGN: Prospective observational study. SETTING: Tertiary care and research center. PATIENT(S): Twenty-nine women with endometriosis and 35 healthy ovulatory volunteers of similar ages. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Expression of immunohistochemical staining intensity and localization of ERalpha, ERbeta, and Brx proteins in eutopic endometrium during the menstrual cycle. RESULT(S): Expression of ERalpha and ERbeta was highest in the proliferative phase and was similar in both groups. Brx expression differed between healthy volunteers and those with endometriosis. During the proliferative phase, immunostaining intensity of Brx was greater in both the glandular and the stromal compartments of biopsies from patients with endometriosis compared to healthy volunteers; nuclear stromal Brx staining was more common in patients with endometriosis. CONCLUSION(S): The spatiotemporal expression of Brx was altered in eutopic endometrium of women with endometriosis. These findings suggest a fundamental alteration in the endometrium of women who have endometriosis. The role of Brx in ectopic implantation of endometrium deserves further study.

A Kinase Anchor Proteins↗

PubMed2006

Macrophage migration inhibitory factor expression in the intrauterine endometrium of women with endometriosis varies with disease stage, infertility status, and pelvic pain.

OBJECTIVE: To evaluate the concentrations of macrophage migration inhibitory factor (MIF) in the eutopic endometrial tissue of women with and without endometriosis. DESIGN: Retrospective study using ELISA to measure MIF concentrations in total endometrial tissue proteins extracts. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Forty-five women with endometriosis and 25 normal women. INTERVENTION(S): Endometrial biopsies were obtained a few days before laparoscopy. MAIN OUTCOME MEASURE(S): Concentrations of MIF in tissue protein extracts. RESULT(S): Levels of MIF were significantly higher in women with endometriosis, increased with disease stage, and were cycle phase dependent. Of note is the significant increase in MIF levels occurring in the midsecretory phase in women with endometriosis as compared with controls, particularly in infertile patients, as well as in the late secretory phase preceding menstruation. Furthermore, MIF levels seemed to be particularly elevated in women with endometriosis who were infertile and who suffered from pelvic pain. CONCLUSION(S): This study showed a significant increase in MIF concentrations in the intrauterine endometrial tissue of women with endometriosis, occurring at specific phases of the menstrual cycle, a relationship between MIF concentrations and disease stage, and a possible role for this factor in endometriosis-associated pain and infertility.

Adult↗

PubMed2006

Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 in follicular fluid accumulate differentially in patients with and without endometriosis undergoing in vitro fertilization.

OBJECTIVE: To compare the amount of regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) in follicular fluid (FF) of patients with and without endometriosis and to determine their oocyte fertilization and pregnancy rates. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Germany. PATIENT(S): Thirty-two women with endometriosis stages I-IV and 28 women without endometriosis, both groups surgically and histologically confirmed. INTERVENTION(S): Diagnostic laparoscopy, IVF-ET. MAIN OUTCOME MEASURE(S): RANTES and MCP-1 levels in follicular fluid, measured by ELISA, and oocyte fertilization and pregnancy rates. RESULT(S): Follicular response and days of gonadotropin stimulation were similar between the two groups. The levels of RANTES in FF from patients with endometriosis were significantly higher (460.4 +/- 90.3 pg/mL) compared with concentrations in patients with tubal infertility (243.8 +/- 70.9 pg/mL; P<.05). In contrast, MCP-1 concentrations in FF from women with endometriosis (330.0 +/- 29.2 pg/mL) were lower than in women with tubal infertility (420.5 +/- 46.6 pg/mL; P<.05). Oocyte fertilization rates in the endometriosis group (54%) were significantly lower than those of the tubal infertility group (73%; P<.05), as were the pregnancy rates (19% vs. 35%, respectively; P<.01). CONCLUSION(S): Women with endometriosis-associated infertility have a poor IVF outcome. Immune cell recruitment into the ovary might affect follicular function and lead to impaired oocyte quality.

Adult↗

PubMed2006

[Abdominal wall endometriosis after caesarean section: report of fifteen cases].

OBJECTIVE: Parietal endometriosis is an uncommon pathology. It can occur on all the scars, most often after a surgical procedure with hysterotomy. Surgical scar endometriosis following caesarean section has an incidence of 0.03 to 0.4%. PATIENTS AND METHODS: This retrospective study reviewed all the cases of parietal endometriosis seen during a 7-year period in the department of visceral surgery of the Armentière's hospital center. A pathological analysis has confirmed each lesion retained. RESULTS: 15 women were treated during this period. The mean age is 32 years. All the women have one or two antecedents of caesarean with Pfannenstiel's laparotomy. The interval between the caesarean and the appearance of the first symptoms is on average of 5 years and 11 months. Only 66.6% of cases presented the classical symptoms with cyclic pain. For 66.6% of patients, the diagnosis of parietal endometriosis was suspected before the treatment. The treatment is a surgical one with exeresis for all the women. In 13.3% of the cases, the lesion is pre aponeurotic. In 46.6% of the cases, it overgrows the rectus abdominis muscle, in 33.3% of the cases the external abdominal oblique and at last a lesion overgrows the transversus abdominis and one is in an inguinal localization. The mean size of lesions is 2.48 cm. We have not notified complications and no recurrence was noted. DISCUSSION AND CONCLUSION: The local endometrial cell transplant is the most likely mechanism to explain the physiopathology of parietal endometriosis. The classical symptoms associate a painful swelling and cyclic pain related to the menstrual period, but all of these symptoms are not always associated. The contribution to the diagnosis of the imaging studies is weak. The surgical treatment has to be sufficiently wide to avoid all recurrence. No means of prevention has proved its efficiency. In 26.6% of cases the parietal endometriosis is associated to pelvic endometriosis. This localization is more often asymptomatic. Then the realization of a laparoscopic exploration is not indicated immediately.

Abdominal Pain↗

PubMedDate not supplied

Clinical and quality-of-life outcomes after fertility-sparing laparoscopic surgery with bowel resection for severe endometriosis.

STUDY OBJECTIVE: To describe the effect of fertility-sparing laparoscopic excision of endometriosis and bowel resection on clinical and quality-of-life outcomes. DESIGN: Prospective observational cohort study (Canadian Task Force classification II-2). SETTING: Australian tertiary referral center for the surgical treatment of endometriosis. PATIENTS: Seven consecutive patients with known endometriosis involving the bowel. INTERVENTION: Laparoscopic resection of all endometriosis, including laparoscopic bowel resection with end-to-end anastomosis with or without temporary ileostomy. MEASUREMENTS AND MAIN RESULTS: Preoperative and 12-month postoperative data were collected by use of visual analogue scores for dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and dyschezia. Validated research tools (SF12, EuroQOL, and Sexual Activity Questionnaire) also assessed quality of life. Reduction in median pain scores at baseline was demonstrated and at 12 months after operation for dysmenorrhea 71 (interquartile range 43-85) versus 5 (0-10); p=.028, nonmenstrual pelvic pain 74 (48-85) versus 11 (0-18); p=.046, dyspareunia 66 (0-98) versus 5 (0-8); p=.080, and dyschezia 48 (20-64) versus 20 (0-40); p=.173. All measures of quality of life were improved at 12 months after surgery, although not reaching statistical significance because of the small sample size. All three women wishing to conceive after operation have been successful, resulting in three live births at term. There were few complications associated with this surgery. CONCLUSION: Fertility-sparing laparoscopic excision of endometriosis with bowel resection results in improvements in all aspects of pain and quality of life. Results appear to parallel published data for conservative resection of endometriosis not involving bowel. For women with severe endometriosis involving bowel, this surgical treatment provides a viable alternative to pelvic clearance and successfully maintains fertility.

Adult↗

PubMedDate not supplied

Challenges to our understanding of endometriosis pain.

Endometriosis remains a diagnostic and therapeutic challenge despite decades of clinical experience and research. The multiple treatment options for endometriosis described in this symposium clearly indicate how difficult it can be to diagnose and effectively treat endometriosis with our current understanding of the disease. At least 3 major challenges to our understanding can be identified: (1) endometriosis does not always cause pain; (2) other causes of pelvic pain often coexists in patients with endometriosis; and (3) common medical and surgical treatments for endometriosis are relatively nonspecific. Insights from the articles in this symposium can help clinicians reach a new level of understanding of endometriosis and perhaps lead to more effective methods for diagnosing and treating this perplexing condition.

Endometriosis↗

PubMed2003

Endometriosis from thelarche to midteens: pathogenesis and prognosis, prevention and pedagogy.

John Huffman, a founder of the subspecialty of pediatric and adolescent gynecology in North America, first related the diagnosis of endometriosis to thelarche. Subsequently, endometriosis was diagnosed in early puberty between thelarche and menarche. Based on solid evidence, we suggest that the theory of embryonic mullerian rests be added to currently accepted theories of pathogenesis of endometriosis. This article argues for recognition of embryonic mullerian rests as the pathogenesis of some cases of endometriosis not explained by accepted theories. Along with Huffman, we propose that thelarche be recognized as a developmental benchmark, after which endometriosis is included in the differential diagnosis of chronic pelvic pain. Thus, in an effort to refocus research and patient care to early adolescence, this review is limited to endometriosis occurring in young women from thelarche to their sixteenth birthday. Relating endometriosis to thelarche has fundamental implications for pathogenesis, early diagnosis, prognosis, treatment, education, and long-term care of adolescents.

Adolescent↗

PubMed2004

No association of endometriosis with glutathione S-transferase M1 and T1 null mutations in a Japanese population.

OBJECTIVE: Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and with environmental factors to produce the phenotype. We investigated the frequency of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) null mutations in women with endometriosis in a Japanese population. METHODS: One hundred fourteen unrelated women with endometriosis were enrolled. Samples of umbilical cord blood obtained from 179 female newborn infants were used as population controls. Genomic DNA isolated from endometriosis patients and controls were subjected to multiple polymerase chain reactions to determine the GSTM1 and GSTT1 genotypes. RESULTS: There were no significant differences in the frequencies of the GSTM1 (P = .83, odds ratio 0.95) and GSTT1 (P = .24, odds ratio 0.75) null mutations between endometriosis patients and controls. The endometriosis group was divided into a subgroup of stage IV disease only, but no statistically significant differences were observed in the frequency of the GSTM1 null mutation (P = .88, odds ratio 0.96, 95% confidence interval 0.57-1.63) and the GSTT1 null mutation (P = .33, odds ratio 0.77, 95% confidence interval 0.45-1.30) between any of these groups and the controls. CONCLUSION: These findings suggest that the GSTM1 and GSTT1 null mutations are not likely to be associated with an increased risk of endometriosis in a Japanese population.

DNA Mutational Analysis↗

PubMed2004

Androgen receptor gene cytosine, adenine, and guanine trinucleotide repeats in patients with endometriosis.

OBJECTIVE: A genetic variation in the androgen receptor (AR) has been associated with the risk of developing endometriosis. The AR gene is located on the X chromosome and contains a highly polymorphic trinucleotide repeat (cytosine, adenine, and guanine: CAG) in its first exon, whose length and methylation pattern affect both AR expression and function. Thus, we sought to further investigate the potential association between endometriosis and the AR-CAG polymorphism. METHODS: Genomic DNA was obtained from a consecutive series of 197 white Italian women of reproductive age who underwent laparoscopy for benign gynecologic pathologies. Molecular analysis of AR-CAG repeats was performed by polymerase chain reaction amplification and Genescan evaluation. The pattern of CAG repeat distribution was compared between subjects with and without endometriosis. RESULTS: Endometriosis was documented in 105 women (stage I-II in 33 women and stage III-IV in 72 women). We found no difference in the number of AR-CAG repeats between women with endometriosis and controls. The CAG repeat length ranged from eight to 27 (mean +/- standard deviation, 17.4 +/- 1.9) for endometriosis patients and from 11 to 27 (mean +/- standard deviation, 17.4 +/- 2) for controls. Moreover, no association was found between AR gene polymorphisms and the various clinical manifestations of the disease. CONCLUSION: We conclude that AR-CAG repeat length does not constitute an important factor for the genetic predisposition to endometriosis.

Adenine↗

PubMed2004

Polymorphism at codon 72 of the p53 gene is not associated with endometriosis in a Japanese population.

OBJECTIVE: Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and the environment to produce the phenotype. Previous studies have implicated p53, a tumor suppressor gene, as a factor in the development of the disease. In a Japanese population, we investigated the frequency of the p53 polymorphism in women affected with endometriosis. METHODS: We compared the distribution of the p53 codon 72 polymorphism in endometriosis cases (n = 111) and population controls consisting of female neonates (n = 180) by using polymerase chain reaction restriction fragment-length polymorphism analysis in a Japanese population. RESULTS: The frequencies of the three p53 genotypes, Arginine (Arg)/Arg, Arg/Proline (Pro), and Pro/Pro in controls were 39.4%, 41.7%, and 18.9 %, respectively. The crude genotype frequencies in the endometriosis cases were similar to those of the controls (35.2%, 48.6%, and 16.2%, respectively). Using the Arg/Arg genotype as the reference, the odds ratios of the Arg/Pro and Pro/Pro genotypes were 1.30 (95% confidence interval [CI] 0.72-1.86, P =.33) and 0.96 (95% CI 0.47-1.94, P =.91), respectively. Thus, there were no significant differences in the frequency of the p53 codon 72 polymorphism between endometriosis cases and controls in this population. The endometriosis cases with severe disease only were also evaluated, but no significant difference was observed in the frequency of the polymorphism between this subgroup and the controls. CONCLUSION: Our findings suggest that the p53 codon 72 polymorphism is unlikely to be associated with endometriosis in Japanese women.

Codon↗

PubMed1992

Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis.

OBJECTIVE: Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity. STUDY DESIGN: The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid. RESULTS: The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable. CONCLUSION: These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis.

Adult↗

PubMed1992

Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results.

OBJECTIVE: We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis. STUDY DESIGN: A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods. RESULTS: When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis. CONCLUSION: Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain.

Adolescent↗

PubMed1987

Effect of pregnancy on surgically induced endometriosis in cynomolgus monkeys.

There are few objective data to support the clinical impression that pregnancy exerts a beneficial effect on endometriosis. In this study, we examined the progression-regression of endometriosis in pregnant and nonpregnant monkeys. Endometriosis was surgically induced in 16 monkeys and classified as minimal (n = 5), mild (n = 5), moderate (n = 4), or severe (n = 2). Monkeys were mated and pregnancy occurred in three monkeys with minimal, three with mild, and one with moderate endometriosis. Laparotomy was performed to stage the disease and to obtain biopsy specimens of implants 1 month post partum or 6 to 8 months after initial operation in nonpregnant monkeys. Monkeys with minimal and mild disease had complete regression of macroscopic disease. Histologic examination of the implants showed only fibrosis and hemosiderin deposits, except in one animal with mild endometriosis containing microscopic foci of endometrial glands. The one monkey with moderate disease had significant, but not complete regression of implants. Endometriosis in nonpregnant monkeys tended to progress. These findings demonstrate that pregnancy does exert a beneficial effect on endometriosis and suggest that pregnancy commonly results in complete resolution of minimal or mild disease.

Animals↗

PubMed1987

Local peritoneal factors: their role in infertility associated with endometriosis.

In order to detect peritoneal abnormalities that could account for infertility associated with endometriosis, 122 infertile individuals were studied at the time of laparoscopy for diagnostic purposes or for in vitro fertilization. Four groups were defined: group 1, laparoscopy without endometriosis; group 2, laparoscopy with endometriosis; group 3, in vitro fertilization without endometriosis; and group 4, in vitro fertilization with endometriosis. Mean peritoneal fluid volume was greater, although not significantly so, in group 4 (29.0 +/- 6.6 ml, mean +/- SEM) than in group 3 (18.2 +/- 2 ml). The concentration and total number of pelvic macrophages were similar for groups 1 and 2. The total number of pelvic macrophages was increased in group 4 (16.9 +/- 4.2 x 10(6)) versus group 3 (10.0 +/- 1.8 x 10(6)) (p = 0.08). The mean sperm phagocytosis in vitro did not differ among the four groups studied. Interleukin 1 activity within the peritoneal fluid and the in vitro interleukin 1 production rate did not differ between individuals with and without endometriosis. Peritoneal fluid and macrophage supernatants from individuals with endometriosis were not embryotoxic when studied in an in vitro mouse embryo system.

Adult↗

PubMed2001

Recurrence of ovarian endometriosis and anatomical location of the primary lesion.

OBJECTIVE: To investigate whether the risk of endometriosis recurrence and pregnancy rate are related to the side of the pelvis on which the primary lesion is found. DESIGN: Cross-sectional study. SETTING: Tertiary institutional hospital. PATIENT(S): One hundred and twenty-one patients with advanced-stage pelvic endometriosis. INTERVENTION(S): Conservative laparoscopic treatment. MAIN OUTCOME MEASURE(S): Endometriosis recurrence and pregnancy rate. RESULT(S): Endometriosis was localized on the left hemipelvis, right hemipelvis, and bilaterally in 47.9%, 33.9%, and 18.2% of patients, respectively. The overall rate of disease recurrence was 17.3%. The recurrence rate was higher when the left ovary was involved than when it was not (29% vs. 7.3%; P<.05). The overall rate of spontaneous pregnancy was 48.1%. The median interval between surgery and occurrence of pregnancy was shorter in patients with endometriosis limited to the right hemipelvis than in those with disease limited to the left side (21 months [range, 12-48 months] vs. 9 months [range, 6-12 months]; P<.01). CONCLUSION(S): The likelihood of disease recurrence is lower when endometriosis is located only on the right side of the pelvis than when the left side is involved. In patients who try to conceive, the time between surgery and occurrence of pregnancy seems to be shorter when the endometriosis is localized in the right hemipelvis.

Adult↗

PubMed2001

Histocompatibility leukocyte antigen-G is not expressed by endometriosis or endometrial tissue.

OBJECTIVE: The immunological mechanisms that support persistence and proliferation of ectopic endometrial implants within the peritoneal cavity of women with endometriosis are unknown. Inhibition of natural killer (NK) and cytotoxic T-cell function has been proposed as a mechanism. We tested the hypothesis that expression of a nonclassical major histocompatibility antigen, HLA-G, might explain the local immunosuppression associated with ectopic endometrium. DESIGN: Nested case-control study of women with and without laparoscopic evidence of endometriosis. SETTING: Reproductive endocrinology clinic at a university hospital. PATIENT(S): Peritoneal fluid specimens from 10 women with revised AFS stage I-IV endometriosis and from 10 age-matched normal controls without laparoscopic evidence of endometriosis were tested for the presence of HLA-G protein. Endometriosis and normal endometrial biopsies from four patients were used to prepare stromal cell cultures directly evaluated for HLA-G protein. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression of HLA-G in peritoneal fluid, tissue, and cell cultures was determined by immunoblotting with a specific monoclonal antibody. RESULT(S): HLA-G protein was not detectable in peritoneal fluid specimens of endometriosis patients or controls. Moreover, ectopic and normal endometrial tissues and stromal cells did not express HLA-G. CONCLUSION(S): Immune cell inhibition in endometriosis must be mediated by factors other than HLA-G.

Amino Acid Sequence↗

PubMed2001

Increased expression of endoglin in the eutopic endometrium of women with endometriosis.

OBJECTIVE: To compare the angiogenic activities of endothelial cells in the eutopic endometrium of women with and without endometriosis. DESIGN: Vessels with active angiogenesis were identified using the monoclonal antibody to endoglin. SETTING: University department of obstetrics and gynecology. PATIENT(S): Twenty women with histologically confirmed endometriosis after laparotomy or laparoscopy. Women with carcinoma in situ of uterine cervix, but no evidence of endometriosis (n = 20), served as control subjects. INTERVENTION(S): Formalin-fixed, paraffin-embedded archival tissues were sectioned and stained. MAIN OUTCOME MEASURE(S): Number of vessels stained with monoclonal antibody to endoglin. RESULT(S): For all menstrual phases, the mean number of vessels with endoglin expression was significantly greater in patients with endometriosis compared with control subjects. In each menstrual phase, a significant difference was observed only during the late secretory phase. Within the group with endometriosis, the mean numbers of vessels with endoglin expression in stages I and II were not different from the numbers in stages III and IV. CONCLUSION(S): This study shows the expression of endoglin in the eutopic endometrium of women with endometriosis is significantly increased and the increase is observed only in the late secretory phase. It is suggested from these findings that activation of angiogenesis in the eutopic endometrium might be a key factor in the pathogenesis of endometriosis.

Adult↗

PubMed2001

Validation study of nonsurgical diagnosis of endometriosis.

OBJECTIVE: To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. DESIGN: Prospective study (study sample); retrospective record review (test sample). SETTING: Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy. PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample). INTERVENTION: The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy. MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample. RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample. CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.

Adult↗