45: Acta Obstet Gynecol Scand. 2004 Aug;83(8):699-706.
Aromatase inhibitors: possible future applications.
Karaer O, Oruc S, Koyuncu FM.
Department of Obstetrics and Gynecology, Celal Bayar University Faculty of Medicine, Manisa , Turkey . oznurkaraer@yahoo.com
In premenopausal women ovaries are the major sites of estrogen production, while in postmenopausal women estrogen is produced by aromatization of ovarian and adrenal androgens in extragonadal sites, mostly in adipose tissue. Aromatase is a cytochrome P450 hemoprotein-containing enzyme complex that catalyzes the rate-limiting step in the conversion of androstenedione and testosterone to estrone and estradiol (E2). Aromatase inhibitors (AIs) have been developed primarily for use in either natural or surgical postmenopausal patients. In premenopausal women, the ovary can overcome the estrogen blockade by reflex increments of luteinizing hormone (LH) and follicle stimulating hormone (FSH), so AIs must be combined with a gonadotropin releasing hormone (GnRH) agonist to prevent the reflex LH and FSH increments. In advanced hormone-dependent breast cancer treatment, AIs have been shown to be superior to tamoxifen. Preliminary evidence also suggests superiority in the adjuvant, neoadjuvant settings and also for breast cancer prevention. AIs have been used in infertility and can increase ovulation rate. Reducing FSH dose, estrogen levels, improving response to FSH, implantation rates, and developing multiple follicles that can be used in in vitro maturation procedures are potential areas that AIs might be used in in assisted reproductive technologies (ART), besides simple ovulation induction. AIs are reported to be successful in treatment of endometriosis, an estrogen-dependent process. The use of AIs in gynecomastia, puberte precox, leiomyoma uteri, some estrogen-dependent cancers (ovarian), endometrial cancer and male infertility are reported; some of the results are promising but more clinical trials are needed. AIs are predicted to become the gold standard in the treatment of estrogen-dependent diseases in reproductive medicine in the near future.
PMID: 15255840 [PubMed – in process]

46: Gynecol Endocrinol. 2004 Mar;18(3):144-51.
Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.
Gallinelli A, Chiossi G, Giannella L, Marsella T, Genazzani AD, Volpe A.
Department of Gynecologic, Obstetric and Pediatric Sciences, University of Modena and Reggio Emilia, Modena, Italy.
The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or re-anastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked imnunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p < 0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p < 0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+ and CD4+ activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.
PMID: 15255283 [PubMed – indexed for MEDLINE]

47: Hum Reprod. 2004 Aug;19(8):1755-9. Epub 2004 Jul 14
Selected food intake and risk of endometriosis.
Parazzini F, Chiaffarino F, Surace M, Chatenoud L, Cipriani S, Chiantera V, Benzi G, Fedele L.
Istituto di Ricerche Farmacologiche ‘Mario Negri’, 20157 Milano, Clinica Ostetrico Ginecologica, Universita di Milano, 20122 Milano and Studi di via Fontana, 20122 Milano, Italy. parazzini@marionegri.it
BACKGROUND: To offer data on the relationship between diet and risk of pelvic endometriosis, we analysed data collected in the framework of two case-control studies. METHODS: Data from two case-control studies conducted in Northern Italy between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of endometriosis, admitted to a network of obstetrics and gynaecology departments in Milan , Brescia and Pavia . Controls were 504 women (median age 34 years, range 20-61) admitted for acute non-gynaecological, non-hormonal, non-neoplastic conditions. RESULTS: Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for higher intake of green vegetables [odds ratio (OR) = 0.3 for the highest tertile of intake] and fresh fruit (OR = 0.6), whereas an increase in risk was associated with high intake of beef and other red meat (OR = 2.0) and ham (OR = 1.8). Consumption of milk, liver, carrots, cheese, fish and whole-grain foods, as well as coffee and alcohol consumption, were not significantly related to endometriosis. CONCLUSIONS: This study suggests a link between diet and risk of endometriosis. Copyright 2004 European Society of Human Reproduction and Embryology
PMID: 15254009 [PubMed – in process]

48: J Chir (Paris). 2004 May;141(3):150-6.
[Abdominopelvic actinomycosis: a tumoral syndrome due to bacterial infection] [Article in French] Sergent F, Marpeau L.
Clinique Gynecologique et Obstetricale, Pavillon Mere-Enfant, Hopital Charles Nicolle – Rouen. Fabrice.Sergent@chu-rouen.fr
The purpose of this review is to define the diagnostic steps and treatment of abdominopelvic actinomycosis. Three cases are described which illustrate the variety of clinical presentations ranging from acute peritonitis to chronic pseudo-tumor. The diagnosis of actinomycosis is rarely made pre-operatively. Bacteriologic culture is seldom helpful and imagery findings are non-specific. The diagnosis is usually made retrospectively based on histologic examination. In women, an intrauterine contraceptive device is often a concomitant factor. Long-term antibiotic treatment (several Months) with high-dose penicillin-based medications is the mainstay of therapy. Despite a high risk of complications, surgery is often necessary both for diagnosis and treatment. Resection or drainage may diminish the dosage and duration of antibiotic therapy, and helps to minimize infectious complications. Actinomycosis should be included in the differential diagnosis of abdominopelvic tumors, inflammatory bowel disease, and endometriosis-particularly in a woman with an intrauterine contraceptive device.
PMID: 15249886 [PubMed – in process]

49: J Chin Med Assoc. 2004 Apr;67(4):197-9.
Continuous abdominal paracentesis for management of late type severe ovarian hyperstimulation syndrome.
Chan CC, Yin CS, Lan SC, Chen IC, Wu GJ.
Department of Obstetrics and Gynecology, Kang-Ning General Hospital , Taipei , Taiwan , ROC.
The ovarian hyperstimulation syndrome (OHSS) is often observed in patients undergoing assisted reproductive technology (ART). In severe form OHSS is a serious and potentially life-threatening. Here we report a 36-year-old woman with primary infertility due to endometriosis who underwent controlled ovarian hyperstimulation. Ten days later, severe late-onset ovarian hyperstimulation syndrome, severe ascites and pulmonary effusion, developed. Continuous abdominal paracentesis of 5000 mL/day was performed on the third day. With this procedure, ascitic fluid was drained efficiently and the patient’s condition improved. This report suggests that early continuous abdominal paracentesis with drainage of ascitic fluid is an efficacious procedure for management of the severe ovarian hyperstimulation syndrome as soon as euvolemia is achieved clinically.
PMID: 15244020 [PubMed – in process]

50: Arch Gynecol Obstet. 2004 Jul 9 [Epub ahead of print] High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid between patients with and without endometriosis.
Matalliotakis IM, Goumenou AG, Mulayim N, Karkavitsas N, Koumantakis EE.
Department of Obstetrics and Gynecology, University of Crete , 714-9 Heraklion, P.O. Box 1393 , Crete , Greece .
OBJECTIVE. In the present study we compared the levels of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid (PF) of patients with and without endometriosis, then assessed the possibility of a correlation among these tumor markers. STUDY DESIGN. Our study was a controlled clinical study of patients undergoing laparoscopy for infertility or other benign gynecology conditions. Peritoneal fluid samples were collected from 65 women with endometriosis and 43 women without pelvic disease. Levels of CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid were determined by immunoradiometric assay. RESULTS. The concentration of CA-125 in PF from patients with endometriosis was significantly higher than that in the control group ( p<0.001); for CA 19-9 and CA 15-3, PF concentrations were not statistically different between these two groups. Women with endometriosis had significantly higher levels of CA-125 in proliferative and secretory phases than the control group ( p<0.001 and p<0.002 respectively); furthermore, in patients with endometriosis the CA 19-9 levels were significantly lower in secretory phase than the proliferative ( p<0.004). The levels of CA-125 were significantly lower in women with tubal ligation, in comparison with infertility or pelvic pain in the control group ( p<0.001). No significant difference was seen in women with infertility or pelvic pain in endometriosis group and the levels of CA-125, CA 19-9, and CA 15-3. We did not find any correlation between the stages of endometriosis and the concentration of CA-125, CA 19-9 and CA 15-3. A significant correlation between the CA 19-9 levels and CA 15-3 in patients with endometriosis was found ( r=0.72, p=0.001). CONCLUSIONS. We found high concentrations of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid of women with and without endometriosis in the Yale series. However, the levels only of CA-125 were higher in women with endometriosis, but without diagnostic value. The role of simultaneously high concentrations of CA 19-9 and CA 15-3 in women with endometriosis needs to be explored further.
PMID: 15243756 [PubMed – as supplied by publisher]

51: Hum Reprod. 2004 Jul 8 [Epub ahead of print] Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model.
Nap AW, Dunselman GA , De Goeij AF, Evers JL, Groothuis PG.
Research Institute Growth and Development (GROW), Department of Obstetrics and Gynaecology, University Maastricht and University Hospital Maastricht , PO Box 5800 , 6202 AZ Maastricht , The Netherlands .
BACKGROUND: Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation of endometrium onto the chicken chorioallantoic membrane ( CAM ) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated the expression of a wide range of MMPs in menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal endometriosis and in endometriosis in the rectovaginal space, as well as the function of MMPs in early lesion formation in the CAM model. METHODS: Expression of MMPs was evaluated by immunohistochemistry and MMP function was studied in the CAM by inhibiting MMP activity during lesion formation. RESULTS: Nearly all MMPs were present in all tissues studied. No significant differences in the expression of a majority of MMPs were found in endometriosis-like lesions in CAMs when compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13 activities significantly impaired endometriosis-like lesion formation in CAMs. CONCLUSIONS: The MMP expression profiles of experimentally induced endometriosis in CAMs and human endometriosis are similar. The prevention of endometriosis-like lesion formation in the CAM by inhibiting MMP activity strongly suggests that MMPs have a function in the early development of endometriotic lesions.
PMID: 15242997 [PubMed – as supplied by publisher]

52: Hum Reprod. 2004 Jul 8 [Epub ahead of print] Soluble factors from human endometrium promote angiogenesis and regulate the endothelial cell transcriptome.
Print C, Valtola R, Evans A, Lessan K, Malik S, Smith S.
Department of Pathology, Cambridge University , Tennis Court Road, Cambridge , CB2 1QP , UK .
BACKGROUND: Angiogenesis and vascular remodeling play critical roles in the cyclical growth and regression of endometrium. They also appear to play roles in the pathogenesis of endometriosis. METHODS and RESULTS: Supernatants were collected from cultured endometrium isolated from women with and without endometriosis. These supernatants induced endothelial cell proliferation and angiogenesis in vitro. They contained vascular endothelial growth factor (VEGF)-A, and their proliferative effects on endothelial cells were partially abrogated by a blocking anti-VEGF-A antibody. Gene array analysis showed that culture supernatants from proliferative phase endometrium, and to a lesser extent secretory phase endometrium, induced significant changes in the transcriptome of endothelial cells. We could not detect any association between endometriosis and the ability of endometrial-derived soluble factors to promote angiogenesis or to regulate the endothelial transcriptome. In addition, we could not detect any association between endometriosis and the concentration of VEGF-A in supernatants from cultured endometrium or in menstrual effluent. CONCLUSIONS: We have shown that endometrium cultured in vitro produced soluble factors, including VEGF-A, that promoted angiogenesis. Proliferative phase endometrium promoted significant endothelial cell transcriptome changes that appear overall to be pro-angiogenic. These transcriptome changes provide insight into the dynamic control of vessel structure on which both eutopic endometrium and endometriotic lesions depend.
PMID: 15242995 [PubMed – as supplied by publisher]

53: Hum Reprod. 2004 Jul 8 [Epub ahead of print] Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis.
Harada M, Osuga Y, Hirata T, Hirota Y, Koga K, Yoshino O, Morimoto C, Fujiwara T, Momoeda M, Yano T, Tsutsumi O, Taketani Y.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo , Tokyo , Japan .
BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction. RESULTS: OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.
PMID: 15242994 [PubMed – as supplied by publisher]

54: Int J Urol. 2004 Jul;11(7):560-562.
Hydronephrosis due to ureteral endometriosis treated by transperitoneal laparoscopic ureterolysis.
Watanabe Y, Ozawa H, Uematsu K, Kawasaki K, Nishi H, Kobashi Y.
Department of Urology, Okayama Rosai Hospital , Okayama , Japan .
Abstract Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 43-year-old multiparous woman who suffered from periodic left loin pain in the terminal period of her menstruation. Excretory urogram demonstrated left hydronephrosis and hydroureter and obstruction of the lower left ureter just inferior to the left sacroiliac joint without urolithiasis. An enhanced computed tomography scan showed soft tissue density mass around the left ureter at the level of the stenosis. She underwent transperitoneal laparoscopic ureterolysis and adhesiotomy of the left ureter under the diagnosis of ureteral endometriosis. Because blueberry spots were clearly observed on the pelvic brim, the fibrous tissue surrounded the ureter was removed with peritoneal bleeding spots. Histological examination of the surrounding tissue confirmed the ectopic endometriosis. Even though retroperitoneoscopy is frequently used for ureteral lesion, transperitoneal laparoscopy has an advantage for resection of ectopic endometriosis surrounding the ureter.
PMID: 15242370 [PubMed – as supplied by publisher]

55: Fertil Steril. 2004 Jul;82(1):255; author reply 255-6.
Treatment of endometriosis without aromatase inhibitors.
Brosens I.
PMID: 15237030 [PubMed – indexed for MEDLINE]

56: Fertil Steril. 2004 Jul;82(1):239-40.
A danazol-loaded intrauterine device decreases dysmenorrhea, pelvic pain, and dyspareunia associated with endometriosis.
Cobellis L, Razzi S, Fava A, Severi FM, Igarashi M, Petraglia F.
A danazol-loaded intrauterine device (IUD) containing 300-400 mg of danazol was inserted for 6 months in a group of women (n = 18) (median age 36.6 years; age range: 30 to 46 years) with a histologic diagnosis of endometriosis, referred for recurrent pelvic pain. Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased after the first month, with a persistent effect during the 6 months of IUD insertion. These results show that a danazol-loaded IUD is an effective conservative therapy for patients with endometriosis-related pelvic pain.
Publication Types:
Clinical Trial Letter
PMID: 15237024 [PubMed – indexed for MEDLINE]

57: Fertil Steril. 2004 Jul;82(1):230-1.
Nerve fibers in ovarian dermoid cysts and endometriomas.
Al-Fozan H, Bakare S, Chen MF, Tulandi T.
No nerve fibers are found in endometriomas or in the endometrioma-containing ovaries. These findings are consistent with our previous report that no correlation exists between the presence of nerve fibers and endometriosis.
Publication Types:
Letter
PMID: 15237020 [PubMed – indexed for MEDLINE]

58: Fertil Steril. 2004 Jul;82(1):97-101.
Elevations in peritoneal fluid macrophage migration inhibitory factor are independent of the depth of invasion or stage of endometriosis.
Mahutte NG, Matalliotakis IM, Goumenou AG, Koumantakis GE, Vassiliadis S, Arici A.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
OBJECTIVE: To quantify levels of macrophage migration inhibitory factor (MIF) in the peritoneal fluid (PF) of women with endometriosis, and to correlate these levels with the extent of disease. DESIGN: Controlled clinical study. SETTING: Academic medical center. PATIENT(S): Peritoneal fluid samples were collected during laparoscopic surgery in 60 women with endometriosis and 16 controls undergoing tubal ligation; 52 of the women with endometriosis had received no hormonal treatment in the 6 months prior to surgery , while 8 were using gonadotropin-releasing hormone (GnRH) agonists. MAIN OUTCOME MEASURE(S): Peritoneal fluid migration inhibitory factor (PF MIF) levels. RESULT(S): Women with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL) than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF levels. Peritoneal fluid MIF levels did not vary significantly between the proliferative and secretory phases of the cycle, and did not distinguish women with endometriosis-associated infertility from women with endometriosis-associated pain. CONCLUSION(S): Peritoneal fluid migration inhibitory factor levels are markedly elevated in women with endometriosis but are independent of the extent of disease.
PMID: 15236996 [PubMed – indexed for MEDLINE]

59: Fertil Steril. 2004 Jul;82(1):93-6.
Elevated angiogenin levels in the peritoneal fluid of women with endometriosis correlate with the extent of the disorder.
Suzumori N, Zhao XX, Suzumori K.
Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicine, Nagoya , Japan . og.n.suz@med.nagoya-cu.ac.jp
OBJECTIVE: To assess the release of angiogenin into peritoneal fluid in women with and without endometriosis by measuring its concentration with reference to disease stage, presence of red lesions, and phase of the menstrual cycle. DESIGN: Retrospective study. SETTING: Nagoya City University Hospital . PATIENT(S): Sixty-four women with endometriosis (n = 38) and cystadenomas (n = 26) for whom surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or laparoscopy. MAIN OUTCOME MEASURE(S): Angiogenin concentrations in the peritoneal fluid, as measured by ELISA. RESULT(S): Angiogenin concentration in the peritoneal fluid was markedly elevated in the endometriosis patients (median 515 ng/mL, interquartile range 151-1763 ng/mL) compared with the cystadenoma (control) patients (195 ng/mL, 98-324 ng/mL), with values correlating with the extent of the disease. No significant differences between the proliferative phase and the secretory phase were observed in either the controls or the endometriosis patients. CONCLUSION(S): The inflammation associated with endometriosis, through increasing levels of peritoneal fluid angiogenin, might promote angiogenesis for progression of the disease and correlate with the extent of the disorder.
PMID: 15236995 [PubMed – indexed for MEDLINE]

60: Fertil Steril. 2004 Jul;82(1):86-92.
CD10 immunohistochemical staining enhances the histological detection of endometriosis.
Potlog-Nahari C, Feldman AL, Stratton P, Koziol DE, Segars J, Merino MJ, Nieman LK.
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda , Maryland 20892-1583 , USA . naharic@mail.nih.gov
OBJECTIVE: To determine whether the use of CD10 immunohistochemistry in addition to hematoxylin and eosin (H&E) staining would increase the sensitivity of surgically suspected endometriosis lesions. DESIGN: Retrospective cohort study. SETTING: Tertiary care government research hospital. PATIENT(S): Thirty-one women with chronic pelvic pain. INTERVENTION(S): Immunohistochemical analysis for CD10 was performed on 108 possible endometriotic lesions and in the corresponding endometrial biopsy samples obtained during laparoscopy. When CD10 immunohistochemistry results were positive, the corresponding H&E section was reviewed to determine if the initial diagnosis should be revised. MAIN OUTCOME MEASURE(S): Histologic diagnosis of endometriosis by adjunctive use of CD10 immunohistochemistry in conjunction with H&E-stained specimens. RESULT(S): In endometrial stroma, CD10 was consistently present. Of the 70 specimens judged negative initially by H&E staining, CD10 staining led to the diagnosis of endometriosis in 11. The addition of CD10 immunohistochemistry detected more positive endometriosis lesions than H&E staining alone (45% vs. 35%). In three women with minimal endometriosis at surgery but initially negative histopathology, CD10 immunohistochemistry changed the histologic diagnosis to endometriosis. CONCLUSION(S): The adjunctive use of CD10 immunohistochemistry improves diagnostic sensitivity for endometriosis, especially for women with minimal disease.
PMID: 15236994 [PubMed – indexed for MEDLINE]

61: Fertil Steril. 2004 Jul;82(1):80-5.
Reduction of apoptosis and proliferation in endometriosis.
Beliard A, Noel A, Foidart JM.
Laboratory of Tumor and Development Biology, University of Liege , Liege , Belgium .
OBJECTIVE: To evaluate whether endometriosis could be related to an impaired balance between apoptosis and proliferation, two processes which could be modulated by hormonal status. DESIGN: Immunohistochemical study. SETTING: Academic research laboratory. INTERVENTION(S): Endometriotic samples obtained from peritoneum of women aged 26-40 years who were undergoing laparoscopy for pain or infertility. MAIN OUTCOME MEASURE(S): Apoptotic cells were detected with the use of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The production of p53 and bcl-2, estrogen and Progesterone (P) receptors, and cellular proliferation were assessed by immunohistochemistry in eutopic and ectopic endometria from 30 patients with endometriosis throughout the menstrual cycle. Results were compared with those from normal endometria from 15 fertile patients. RESULT(S): Endometriotic lesions were characterized by reduced TUNEL and p53 stainings and by enhanced bcl-2 staining. No correlation between apoptosis and estrogen receptor or P receptor levels was found. A lower amount of steroid receptor was found in endometriotic tissues, without cyclic modulation, compared with the eutopic endometrium. CONCLUSION(S): Our results suggest that when endometrial tissue is located at ectopic locations, it differs from eutopic endometrium by its proliferation rate, steroid hormone levels, and markers of apoptosis. A reduced sensitivity of endometriotic cells to apoptosis could promote the dissemination and implantation of these cells to ectopic sites.
PMID: 15236993 [PubMed – indexed for MEDLINE]

62: Fertil Steril. 2004 Jul;82(1):45-51.
Prediction of an ongoing pregnancy after intrauterine insemination.
Steures P, van der Steeg JW, Mol BW, Eijkemans MJ, van der Veen F, Habbema JD, Hompes PG, Bossuyt PM, Verhoeve HR, van Kasteren YM, van Dop PA; CECERM (Collaborative Effort in Clinical Evaluation in Reproductive Medicine).
Department of Obstetrics and Gynecology, Vrije Universiteit Medical Center , Amsterdam , The Netherlands . pn.steures@amc.uva.nl
OBJECTIVE: To develop a prognostic model for the outcome of IUI. DESIGN: Retrospective cohort study. SETTING: Four fertility centers in The Netherlands. PATIENT(S): Couples of whom the female partners had a regular cycle and who had been treated with IUI. INTERVENTION(S): Intrauterine insemination with and without ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy. RESULT(S): Overall, 3371 couples were included who underwent 14968 cycles. There were 1229 (8.2%) pregnancies, of which 1000 (6.7%) pregnancies were ongoing. Logistic regression analysis demonstrated that increasing maternal age, longer duration of subfertility, presence of male factor subfertility, one-sided tubal pathology, endometriosis, uterine anomalies, and an increasing number of cycles were unfavorable predictors for an ongoing pregnancy. Cervical factor and the use of ovarian hyperstimulation were favorable predictors. The area under the receiver operating characteristic curve was 0.59. When couples were divided into four categories based on prognosis, the difference between the predicted and observed chance, that is, the calibration, was less than 0.5% in each of the four groups. CONCLUSION(S): Although our model had a relatively poor discriminative capacity, data on calibration showed that the selected prognostic factors allow distinction between couples with a poor prognosis and couples with a good prognosis. After external validation, this model could be of use in patient counseling and clinical decision making.
Publication Types:
Multicenter Study
PMID: 15236988 [PubMed – indexed for MEDLINE]

63: Curr Opin Obstet Gynecol. 2004 Aug;16(4):299-303.
The effectiveness of laparoscopic excision of endometriosis.
Garry R.
University of Western Australia , School of Women ‘s and Infants’ Health, King Edward Memorial Hospital , Subiaco , Western Australia .
PURPOSE OF REVIEW: The optimum method for the treatment of endometriosis remains unclear. This review explores recent data concerning the effectiveness of laparoscopic excision and associated therapies, to guide clinicians in their selection of the most appropriate therapeutic regimen. RECENT FINDINGS: Large, long-term, prospective studies and a placebo-controlled, randomized, controlled trial suggest that laparoscopic excision is an effective treatment approach for patients with all stages of endometriosis. The result of such laparoscopic excision may be improved if affected bowel, bladder and other involved structures are also excised. Adjuvant therapies such as the levonorgestrel intrauterine system and pre-sacral neurectomy may further improve outcomes. Ovarian endometrioma are invaginations of the uterine cortex, and surgical stripping of this cortex removes many primordial follicles. Despite this apparent disadvantage, stripping of the capsule is associated with better subsequent pregnancy rates and lower recurrence rates than the more conservative approach of thermal ablation to the superficial cortex. SUMMARY: Laparoscopic excision is currently the ‘gold standard’ approach for the management of endometriosis, and results may be improved with careful use of appropriate techniques and suitable adjuvant therapies.
PMID: 15232483 [PubMed – as supplied by publisher]

64: Hum Reprod. 2004 Sep;19(9):2126-31. Epub 2004 Jun 30.
Clinical predictive factors for endometriosis in a Portuguese infertile population.
Calhaz-Jorge C, Mol BW, Nunes J, Costa AP.
Human Reproduction Unit, Department of Obstetrics and Gynaecology, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal and Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands.
BACKGROUND: Endometriosis is an important clinical situation associated with subfertility. It would be very useful to identify patients at increased risk for endometriosis prior to laparoscopy. In the present study, we evaluate the demographic and clinical characteristics in a cohort of Portuguese subfertile women in relation to the presence of endometriosis. METHODS: Consecutive subfertile patients scheduled for laparoscopy were interviewed prior to the procedure. At subsequent laparoscopy, the presence of endometriosis was scored according to the revised classification of the American Society for Reproductive Medicine (ASRM). Data available from the medical history were tabulated against the presence or absence of endometriosis. We used logistic regression analysis to evaluate whether data from the patient’s medical history could predict the presence of endometriosis. RESULTS: Among the 1079 women that were studied, 358 had minimal/mild endometriosis and 130 had moderate/severe endometriosis. Primary subfertility, regularity of menstrual cycles, dysmenorrhoea, chronic pelvic pain, obesity, ever use of oral contraceptives and smoking were the most important predictors of endometriosis. The prediction model had an area under the receiver operating characteristic curve of 0.71. CONCLUSIONS: Both the presence of endometriosis (all stages) and the presence of severe endometriosis per se can be predicted from the medical history. These data should be used in the decision to perform laparoscopy at an early stage or a later stage in the work-up for subfertility.
PMID: 15229202 [PubMed – in process]

65: Ginecol Obstet Mex. 2003 Nov;71:559-74.
[Endometriosis and discouragement of immunology cytotoxic characteristics] [Article in Spanish] Hernandez Guerrero CA, Tlapanco Barba R, Ramos Perez C, Velazquez Ramirez N, Castro Eguiluz D, Cerbulo Vazquez A.
Departamento de Ultramicroscopia, Instituto Nacional de Perinatologia.
OBJECTIVE: To determine the immunology kind of response Th1 (cytotoxic) or Th2 (humoral) prevailing at peripheral and peritoneal environment at endometriosis women (ENW). STUDY DESIGN: Observational, transverse, analytical, retrospective, cases and controls. MATERIAL AND METHODS: Cooperative and cytotoxic lymphocytes obtained from peritoneal fluid (PF) and peripheral blood (PB) were used to determine IFN-gamma and IL-2 intracellular synthesis at ENW. IFN-gamma, IL-2, IL-4 and IL-10 concentration were determined at PF, PB at ENW and fertile women (FERW). Results were analyzed by ANOVA, t student and Mann-Whitney tests, accepting p < 0.05, as a statistic difference. RESULTS: Peritoneal environment of ENW shows a smaller intracellular synthesis of IFN-gamma and IL-2 at cooperative and cytotoxic T lymphocytes, as in the PF at ENW. The decrease is associated to a smaller percentage of activated, cooperative T lymphocytes and NK cells (p < 0.05, at all the variable), versus FERW. This phenomenon is observed more stressed at the III and IV pathology degree. CONCLUSIONS: ENW show a peritoneal environment with a smaller immunology cytotoxic capacity, versus FERW. The discouragement of the immunology cytotoxic capacity increases associated to the pathology intensity.
PMID: 15228015 [PubMed – in process]

66: Acta Obstet Gynecol Scand. 2004 Jul;83(7):691-2; author reply 693.
The statistical analysis of women with endometriosis.
Tsakok AD.
PMID: 15225199 [PubMed – indexed for MEDLINE]

67: Acta Obstet Gynecol Scand. 2004 Jul;83(7):651-5.
Ovarian stimulation for in vitro fertilization in patients with endometriosis.
Zikopoulos K, Kolibianakis EM, Devroey P.
Center for Reproductive Medicine, Dutch-Speaking Brussels Free University, Brussels , Belgium .
The use of gonadotropin-releasing hormone (GnRH) agonists in a long protocol appears to enhance the probability of conception in the presence of endometriosis. In addition, there is evidence to suggest that the use of prolonged downregulation with GnRH agonists prior to ovarian stimulation for in vitro fertilization (IVF) is beneficial for achieving pregnancy. Until now, GnRH antagonists have not been used in patients with endometriosis. The management of endometriomas prior to stimulation for IVF and its impact on reproductive outcome are still subject to debate.
Publication Types:
Review Review, Tutorial
PMID: 15225190 [PubMed – indexed for MEDLINE]

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