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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001019.

Update of:

Cochrane Database Syst Rev. 2000;(2):CD001019. 

Modern combined oral contraceptives for pain associated with endometriosis.

Davis L, Kennedy SS, Moore J, Prentice A.

Picker Institute Europe, King’s Mead House, Oxpens Road, Oxford, UK, OX1 1RX. ljd_456@yahoo.com

BACKGROUND: Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The modern oral contraceptive pill is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited. OBJECTIVES: To assess the effects of the oral contraceptive pill (OCP) in comparison to other treatments for painful symptoms of endometriosis in women of reproductive age. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials; Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2006); MEDLINE (January 1966 to September 2006); EMBASE (1980 to September 2006); National Research Register; and reference lists of articles. SELECTION CRITERIA: All truly randomised controlled trials of the use of oral contraceptive pills in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis and made visually at surgical procedure were included. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction were carried out independently by two review authors. One of the assessors was an expert in the content matter. We contacted study authors for additional information. MAIN RESULTS: Only one study met the inclusion criteria, in which a total of 57 women were allocated to two groups to compare an OCP to a GnRH analogue. Methods of randomisation and allocation concealment were unclear and the study was acknowledged by its authors to be underpowered. Women in the GnRH analogue group became amenorrhoeic during the treatment period of six months, whilst women in the OCP group reported a decrease in dysmenorrhoea. No evidence of a significant difference between the two groups was observed in terms of dysmenorrhoea at six months follow up after stopping treatment (OR 0.48; 95% CI 0.08 to 2.90). Some evidence for a decrease in dyspareunia was found at the end of treatment in women in the GnRH analogue group, although no evidence of a significant difference in dyspareunia was observed at the end of the six months follow up (OR 4.87; 95% CI 0.96 to 24.65). AUTHORS’ CONCLUSIONS: The limited data we found available suggests that this is no evidence of a difference in outcomes between the the oral contraceptive pill (OCP) studied and GnRH analogue was as effective as a GnRH analogue in treating for endometriosis-associated painful symptoms of endometriosis. However, the lack of studies with larger sample sizes, or focusing on other comparable treatments is concerning and further research is needed to fully evaluate fully the role of OCPs oral contraceptive pills in managing symptoms associated with ement of endometriosis.

Cochrane Database Syst Rev. 2007 Jul 18;(2):CD000346.

Update of:

Cochrane Database Syst Rev. 2000;(2):CD000346.

WITHDRAWN: Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

Prentice A, Deary AJ, Goldbeck-Wood S, Farquhar C, Smith SK.

Rosie Maternity Hospital, Department of Obstetrics and Gynaecology, Robinson Way, Cambridge, UK, CB2 2SW. ap128@cam.ac.uk

BACKGROUND: Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). OBJECTIVES: To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. SELECTION CRITERIA: Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. DATA COLLECTION AND ANALYSIS: Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are five studies comparing GnRHas with GnRHas plus add-back therapy, three comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo.Data was extracted independently by two reviewers. The authors of eleven studies have been contacted to clarify missing or unclear data. Only four have replied to date.Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. MAIN RESULTS: No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. AUTHORS’ CONCLUSIONS: There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000155.

Update of:

Cochrane Database Syst Rev. 2003;(3):CD000155.

Ovulation suppression for endometriosis.

Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P.

McMaster University, Department of Obstetrics and Gynaecology, 1200 Main St West, Room HSC-4F7, Hamilton, Ontario, Canada L8N 3Z5. hughese@mcmaster.ca

BACKGROUND: Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility. OBJECTIVES: To assess the effectiveness of ovulation suppression agents, including danazol, progestins and oral contraceptives, in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes including live birth. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Sub-fertility Group’s specialised register of trials (searched October 5th, 2007) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), MEDLINE (1966-October 2007), EMBASE (1980 – October 2007) and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception in women with endometriosis. A total of twenty three RCTs comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed quality. We contacted study authors for additional information. Quality was assessed by of method of randomization,allocation concealment, blinding, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using the I(2) test of heterogeneity. Subgroup analysis was conducted on those couples clearly identifiable as infertile or wanting to conceive. MAIN RESULTS: Twenty four trials were included. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment for all women randomised was 0.79 (95% CI 0.54 to 1.14), P = 0.21 and 0.80 (95% CI 0.51 to 1.24), P = 0.32 respectively for subfertile couples only despite the use of a variety of suppression agents. There was no evidence of benefit from the treatment. The common odds ratio for pregnancy following all agents versus danazol for all women randomised was 1.38 (95% CI 1.05 to 1.82), P = 0.02 and OR 1.37 (95% CI 0.94 to 1.99), P = 0.10 for subfertile couples only. When GnRHa and danazol were directly compared, OR was 1.45 (95% CI 1.08 to 1.95) P = 0.01 for all women randomised and OR 1.63( 95% CI 1.12 to 2.37), P = 0.01 for subfertile couples only in favour of GnRH. No effect was observed for GnRH compared with oral contraception; OR 0.99 (95% CI 0.52 to 1.89), P = 0.98 for all women randomised and OR 0.79 ( 95% CI 0.37 to 1.69), P = 0.55. In all analyses the data were statistically homogeneous (I(2)=0%). AUTHORS’ CONCLUSIONS: There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.

Hum Reprod. 2007 Sep;22(9):2359-67. Epub 2007 Jul 18.

Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the menstrual reflux theory.

Vercellini P, Abbiati A, Viganò P, Somigliana ED, Daguati R, Meroni F, Crosignani PG.

Department of Obstetrics and Gynaecology, Istituto Luigi Mangiagalli, University of Milan, Milan, Italy. paolo.vercellini@unimi.it

BACKGROUND: If the menstrual reflux or implantation theory of endometriosis is true, refluxed endometrial cells could reach the right hypochondrium transported by the clockwise peritoneal fluid current and would implant more easily on the right diaphragmatic leaf as they are stuck there by the falciform ligament. METHODS: To investigate if a lateral asymmetry exists in diaphragmatic endometriotic lesion distribution, all articles on diaphragmatic endometriosis identified by MEDLINE, EMBASE and PUBMED database searches were retrieved, and additional reports were collected by systematically reviewing all references. The number of women and the side of the lesion with respect to the falciform ligament of the liver were obtained from individual studies, and the combined frequency of right- and left-side diaphragmatic endometriosis was computed. In addition, seven personal cases were described. RESULTS: There were 16 reports including 47 subjects selected. Diaphragmatic endometriosis was on the right side in 31 (66%) patients, on the left in 3 (6%) and bilateral in 13 (27%). In the personal series, lesions were on the right side in five cases, on the left in one and bilateral in one. Considering only unilateral lesions, the observed proportion of right-sided endometriotic implants (36/40) was 90% (95% CI 76-97%; chi(2)(1) 32.6, P < 0.0001). CONCLUSIONS: The observed major asymmetry in diaphragmatic endometriotic lesion distribution in favour of the right leaf supports the menstrual reflux theory.

Reprod Sci. 2007 Apr;14(3):270-9.

Effect of caffeic acid phenethyl ester on the regression of endometrial explants in an experimental rat model.

Güney M, Nasir S, Oral B, Karahan N, Mungan T.

Department of Obstetrics and Gynecology, Suleyman Demirel University, Isparta, Turkey. mguney@med.sdu.edu.tr

The objective of this study is to determine the effects of antioxidant and anti-inflammatory caffeic acid phenethyl ester (CAPE) on experimental endometriosis, peritoneal superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) levels in the rat endometriosis model. Thirty rats with experimentally induced endometriosis were randomly divided into 2 groups and treated for 4 weeks with intraperitoneal CAPE (CAPE-treated group; 10 micromol/kg/d, n = 13) or vehicle (control group; n = 13). The volume and weight changes of the implants were calculated. Immunohistochemical and histologic examinations of endometriotic explants by semiquantitative analysis and measurements of peritoneal SOD, CAT, and MDA levels were made. Following 4 weeks of treatment with CAPE, there were significant differences in posttreatment spherical volumes (37.4 +/- 14.7 mm(3) vs 147.5 +/- 41.2 mm(3)) and explant weights (49.1 +/- 28.5 mg vs 158.9 +/- 50.3 mg) between the CAPE-treated groups and controls. The mean evaluation nomogram levels in glandular epithelium for COX-2 positivity by scoring system were 2.1 +/- 0.3 in the CAPE-treated group and 3.9 +/- 0.3 in the control group. In the CAPE-treated group, peritoneal levels of MDA and activities of SOD and CAT significantly decreased when compared with the control group (P < .01). Histologic analysis of the explants demonstrated mostly atrophy and regression in the treatment group, and semiquantitative analysis showed significantly lower scores in rats treated with CAPE compared with the control group. CAPE appeared to cause regression of experimental endometriosis.

Reprod Sci. 2007 Feb;14(2):137-50.

Erratum in:

Reprod Sci. 2007 May;14(4):390-4.

The altered distribution of the steroid hormone receptors and the chaperone immunophilin FKBP52 in a baboon model of endometriosis is associated with progesterone resistance during the window of uterine receptivity.

Jackson KS, Brudney A, Hastings JM, Mavrogianis PA, Kim JJ, Fazleabas AT.

Department of Obstetrics and Gynecology (MC808), College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

This study examines the distribution of estrogen receptors (ESR), progesterone receptors (Pgr), and the chaperone immunophilin FKBP52 in the eutopic endometrium in a baboon model of endometriosis during the window of receptivity to determine if their aberrant distribution contributes to reduced fecundity. Endometriosis was induced by inoculation of menstrual endometrium into the peritoneal cavity. Eutopic endometrium was collected at 3, 6, 9, 12, and 15 months postinoculation. Western blot (WB) and immunohistochemical analyses were performed. Isolated endometrial stromal cells were cultured in the presence or absence of steroid hormones. In animals with endometriosis, ESR-1 (ER-alpha) decreased in endometrial stromal cells, while ESR-2 (ER-beta) was reduced in both glandular epithelial (GE) and stromal cells. Immunoreactive total Pgr was markedly diminished in the GE, which was confirmed by WB analysis. Furthermore, treatment of isolated stromal cells from baboons with endometriosis with hormones did not increase levels of PRA or PRB as in control baboons. FKBP52 was also reduced in the eutopic endometrium of baboons with endometriosis. Endometriosis results in an aberrant distribution of ESR-1, ESR-2, Pgr, and FKBP52 in the eutopic endometrium. The authors propose that a dysregulation in the paracrine signaling between the endometrial stromal and GE cells reduces the responsiveness of Pgr, creating an endometrial environment that is unsuitable for implantation.

Headache. 2007 Jul-Aug;47(7):1069-78.

Endometriosis is associated with prevalence of comorbid conditions in migraine.

Tietjen GE, Bushnell CD, Herial NA, Utley C, White L, Hafeez F.

Department of Neurology, University of Toledo Medical Center, Health Science Campus, 3120 Glendale Avenue, Toledo, OH 43614, USA.

OBJECTIVE: To examine the headache characteristics of women with migraine and endometriosis (EM), and differences in the prevalence of comorbid conditions between female migraineurs with EM, without EM and nonheadache controls. BACKGROUND: Migraine and EM are common conditions in women of reproductive age, and both are influenced by ovarian hormones. The comorbidity of migraine and EM is newly recognized, but reasons for the association are uncertain. METHODS: This is a cross-sectional study of female headache outpatients and healthy controls conducted at University of Toledo and Duke University in 2005 and 2006. After a headache specialist determined headache frequency and diagnosis (based on criteria of the second International Classification of Headache Disorders), patients completed a self-administered electronic survey with information on demographics, headache-related disability, menstrual disorders, premenstrual dysphoric disorder (PMDD), vascular event risk, and comorbid conditions, including irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), interstitial cystitis (IC), depression, and anxiety. RESULTS: Study enrolled 171 women with migraine and 104 controls. EM was reported more commonly in migraineurs than in controls (22% vs 9.6%, P < .01). Frequency of chronic headache was higher in migraineurs with EM compared to without EM (P= .002) and median headache-related disability scores were also higher in the EM group (P= .025). Symptoms of PMDD were more common in migraineurs, but frequency did not differ by EM status. Migraineurs with EM reported more menorrhagia, dysmenorrhea, and infertility compared to the migraine cohort without EM and to controls. Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls. Anxiety (OR = 2.2, 95% CI 1.0-4.7), IC (OR = 10.6, 95% CI 1.9-56.5), and CFS (OR = 3.6, 95% CI 1.1-11.5) were more common in migraine with EM group, than in the cohort with migraine without EM. CONCLUSION: Prevalence of EM is higher in women with migraine than in nonheadache controls. Migraineurs with EM have more frequent and disabling headaches, and are more likely to have other comorbid conditions affecting mood and pain, compared to migraineurs without EM.

Gynecol Oncol. 2007 Nov;107(2):248-52. Epub 2007 Jul 12.

Accuracy of intraoperative frozen section analysis in borderline tumors of the ovary: a retrospective analysis of 96 cases and review of the literature.

Tempfer CB, Polterauer S, Bentz EK, Reinthaller A, Hefler LA.

Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

OBJECTIVE: To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of borderline tumors of the ovary (BTO). METHODS: Retrospective analysis at the Department of Obstetrics and Gynecology, University of Vienna, between 1995 and 2007 and review of the literature. Frozen section analysis and definitive histology reports were compared. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis. RESULTS: Agreement between frozen section diagnosis and definitive histology was observed in 69/96 (71.9%) patients, yielding an overall sensitivity and a positive predictive value of 75.0% and 94.5%, respectively. Underdiagnosis and overdiagnosis occurred in 27/96 (28%) and 0/96 (0%) patients, respectively. In a univariate and multivariate analysis, tumor diameter, but not patient age, tumor histology, tumor stage, presence of a bilateral tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis of frozen section analysis. We identified 29 studies investigating the accuracy of frozen section analysis of BTO. Three studies exclusively examined BTO in 140, 48 and 33 cases, respectively. Data of these three studies and the present study were pooled, yielding an overall sensitivity and PPV of 71.1% and 84.3%, respectively. Overdiagnosis and underdiagnosis were identified in 21/317 (6.6%) and in 97/317 (30.6%) cases, respectively. CONCLUSION: Intraoperative frozen section diagnosis of BTO has a low sensitivity and PPV and overdiagnosis and underdiagnosis are frequent. Surgical management based on intraoperative frozen section diagnosis should be used with caution.

Am J Reprod Immunol. 2007 Aug;58(2):75-97.

Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1.

D’Cruz OJ, Uckun FM.

Drug Discovery Program, Paradigm Pharmaceuticals, St Paul, MN 55113, USA. dcruz915@comcast.net

Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.

Hum Reprod Update. 2007 Nov-Dec;13(6):567-80. Epub 2007 Jul 14.

Progesterone receptor modulators and the endometrium: changes and consequences.

Horne FM, Blithe DL.

Rose Li & Associates, Inc., Bethesda, MD 20817, USA.

Progesterone receptor modulators (PRMs) have been used for contraceptive research, as well as for treatment of fibroids, endometriosis and heavy or irregular menstrual bleeding. Long-term treatment with these compounds results in changes to the endometrium resulting in potential confusion in trying to characterize endometrial biopsies. A meeting was held to discuss the properties of PRMs, the effects of perturbed hormonal control of the endometrium and the need for further understanding of the biology of progesterone receptor action to facilitate the development of new PRMs. A panel of pathologists was convened to evaluate endometrial changes associated with a minimum of three months of chronic treatment with PRMs. Four different agents were used in the treatment regimens but the pathologists were blinded to treatment regimen or agent. The panel agreed that the endometrial biopsies did not fit into a classification of either proliferative or secretory endometrium but exhibited an unusual architecture that could be characterized as glandular dilatation. There was little evidence of mitosis, consistent with a proposed anti-proliferative effect of PRMs. The panel concluded that the biopsies did not reveal evidence of safety concern and that pathologists and investigators familiar with endometrial effects of chronic PRM exposure should consider working with pharmaceutical companies and regulatory agencies to develop standard descriptions of PRM-associated endometrial changes as well as the types of histologic changes that would signal a need for intervention.

J Minim Invasive Gynecol. 2007 Jul-Aug;14(4):531-2; author reply 532-3.

Comment on:

J Minim Invasive Gynecol. 2007 Jan-Feb;14(1):49-53.

Abuzeid et al. Fimbrial pathology.

Cohen BM.

J Minim Invasive Gynecol. 2007 Jul-Aug;14(4):463-9.

Laparoscopic treatment of deep endometriosis with segmental colorectal resection: short-term morbidity.

Mereu L, Ruffo G, Landi S, Barbieri F, Zaccoletti R, Fiaccavento A, Stepniewska A, Pontrelli G, Minelli L.

Department of Obstetrics and Gynecology, Ospedale Sacro Cuore, Negrar-Verona, Italy. liliana_mereu@yahoo.com

STUDY OBJECTIVE: Adequate surgical treatment of severe deep endometriosis requires complete excision of all implants, but the modality of bowel resection is still debated. We describe the results of our experience as a tertiary care endometriosis referral center in complete laparoscopic management of deep pelvic endometriosis with bowel involvement. DESIGN: A prospective single-center study (Canadian Task Force classification II-1). SETTING: In Sacro Cuore General Hospital of Negrar, Italy. PATIENTS: One hundred ninety-two women treated with laparoscopic excision of deep endometriosis and segmental colorectal resections were evaluated. INTERVENTION: From January 2003 through December 2005 we registered all consecutive patients laparoscopically treated for deep endometriosis who also were having segmental bowel resection. MEASUREMENTS AND MAIN RESULTS: Data analysis included age, weight, body mass index, history of endometriosis, preoperative symptoms, parity, infertility, operative procedures, operating time, conversion, intraoperative and postoperative morbidity, recovery of bladder and bowel function, and discharge from hospital. We report our results in terms of feasibility and short-term morbidity. Radicality was achieved in 91.5% of patients. Laparoconversion occurred in 5 cases (2.6%). Major complications that required repeat operation occurred in 20 cases (10.4%): Nine anastomosis leakages (4.7%), 3 uroperitoneum (1.6%), 4 hemoperitoneum (2.1%), 1 pelvic abscess (0.5%), 1 bowel perforation, 1 intestinal obstruction, and 1 sepsis. Minor complications occurred in 50 patients (26%). CONCLUSION: Laparoscopic segmental colorectal resection for endometriosis is feasible and, in hospitals with necessary experience, can be proposed to selected patients who are informed of the risk of complications.

J Minim Invasive Gynecol. 2007 Jul-Aug;14(4):393-4.

Narrow band imaging in endometriosis.

Farrugia M, Nair MS, Kotronis KV.

East Kent Hospitals NHS Trust, London, United Kingdom. martin@farrugia.demon.co.uk

Ann Diagn Pathol. 2007 Aug;11(4):252-7.

Adenomyosis involved by endometrial adenocarcinoma is a significant risk factor for deep myometrial invasion.

Ismiil N, Rasty G, Ghorab Z, Nofech-Mozes S, Bernardini M, Ackerman I, Thomas G, Covens A, Khalifa MA.

Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada M4N 3M5. nadia.ismiil@sw.ca

Adenomyosis is commonly seen in association with endometrial adenocarcinoma where it may or may not be involved by malignancy. This study of grade 1 endometrioid adenocarcinoma investigates whether patients with cancer-positive adenomyosis are at a different risk for deep myometrial invasion compared with those with cancer-negative adenomyosis. Ninety-three hysterectomy specimens with FIGO (International Federation of Gynecologists and Obstetricians) grade 1 endometrial endometrioid adenocarcinoma associated with adenomyosis were studied. Four experienced gynecologic pathologists retrospectively reviewed all hematoxylin and eosin-stained sections. Myometrial invasion was confirmed by CD10-negative staining around glands with jagged outline surrounded by inflamed desmoplastic stroma. Adenomyosis was involved by adenocarcinoma in 46 cases, whereas it was carcinoma-negative in 47 cases. Myometrial invasion was found in significantly more carcinoma-positive adenomyosis cases (n = 42, 91.3%) than with carcinoma-negative adenomyosis cases (n = 30, 63.8%) (chi(2) = 12.10; P = .0005). Moreover, myometrial invasion in the outer half was also seen in significantly more carcinoma-positive adenomyosis cases (n = 16, 34.8%) than with carcinoma-negative adenomyosis cases (n = 3, 6.4%) (chi(2) = 11.53; P = .0007). Among all cases of FIGO grade 1 endometrial endometrioid adenocarcinoma associated with adenomyosis, the ones that extend in the adenomyosis gain more invasive advantage, probably through increasing the surface area of its interface with the adjacent myometrium. When compared with tumors that do not involve adenomyosis, these tumors are not only more likely to invade the myometrium but are significantly more prone to achieve deep invasion into the outer half.

Clin Exp Obstet Gynecol. 2007;34(2):123-5.

Endometriosis: rare localizations in two cases.

Mascaretti G, Di Berardino C, Mastrocola N, Patacchiola F.

Department of Obstetrics and Gynecology, Faculty of Medicine and Surgery, University of L’Aquila, Italy.

Endometriosis is a disease in continuous evolution due to its various aspects and atypical localizations. Every year many women all over the world are affected by it. In typical localizations the diagnosis is simple; the symptoms include pelvic pain and in most of cases sterility. In rare localizations the symptoms are non-specific and the diagnosis is difficult. In particular an intestinal isolated localization is often asymptomatic or can cause non-specific pelvic pain, irregular intestinal activity and in such case, a subocclusive condition often with a diagnosis of inflammatory bowel disease. Two cases of rare localizations of endometriosis are described in the intestinal wall and a cesarean section scar. An analysis of the etiopathogenesis and diagnostic approach in these rare localizations is presented.

Clin Exp Obstet Gynecol. 2007;34(2):113-4.

Ovarian ossification associated with endometriosis.

Shaco-Levy R, Lazer T, Piura B, Wiznitzer A.

Department of Pathology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

BACKGROUND: Bone formation in the ovary, with the exception of developing in the setting of mature cystic teratoma, is exceedingly rare. CASE: A 46-year-old woman with a history of endometriosis and chronic pelvic pain underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. A 3 cm solid heavily calcified mass with a stony hard consistency was detected within the right ovary. Microscopic examination revealed extensive calcification of the right ovarian stroma with formation of abundant mature bone, adjacent to small foci of endometriosis. CONCLUSIONS: Endometriosis can be associated with ovarian ossification, forming an extensively calcified adnexal mass. Conservative treatment with close follow-up may be adequate in patients with a history of endometriosis who present with a small heavily calcified ovarian mass and wish to preserve their fertility.

Clin Exp Obstet Gynecol. 2007;34(2):123-5.

Endometriosis: rare localizations in two cases.

Mascaretti G, Di Berardino C, Mastrocola N, Patacchiola F.

Department of Obstetrics and Gynecology, Faculty of Medicine and Surgery, University of L’Aquila, Italy.

Endometriosis is a disease in continuous evolution due to its various aspects and atypical localizations. Every year many women all over the world are affected by it. In typical localizations the diagnosis is simple; the symptoms include pelvic pain and in most of cases sterility. In rare localizations the symptoms are non-specific and the diagnosis is difficult. In particular an intestinal isolated localization is often asymptomatic or can cause non-specific pelvic pain, irregular intestinal activity and in such case, a subocclusive condition often with a diagnosis of inflammatory bowel disease. Two cases of rare localizations of endometriosis are described in the intestinal wall and a cesarean section scar. An analysis of the etiopathogenesis and diagnostic approach in these rare localizations is presented.

Clin Exp Obstet Gynecol. 2007;34(2):96-8.

Effects of micronized purified flavonoid fraction (Daflon) on pelvic pain in women with laparoscopically diagnosed pelvic congestion syndrome: a randomized crossover trial.

Simsek M, Burak F, Taskin O.

Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey.

BACKGROUND: We evaluated the effects of daflon, a venomimetic agent that regulates the circulatory tonus of the venous system, on pelvic pain and investigated the role of enlarged veins in the pathophysiology of pelvic congestion syndrome. METHODS: Twenty women (age 28-35 yrs) with chronic pelvic pain were diagnosed with the syndrome at laparoscopy. They all had prominent broad ligaments and ovarian veins without other pathologies such as endometriosis to explain the etiology of pelvic pain. Ten women were randomized in a fashion to receive 500 mg of Daflon twice/daily for six months, and ten a vitamin pill for placebo effect; they were crossed over for another six months. RESULTS: At the end of the third month, the frequency and severity of pelvic symptoms began to decrease with daflon compared with the pretreatment and vitamin arm. The mean scores were significantly less at the end of six months, respectively, p < 0.05. CONCLUSIONS: Pharmacologic enhancement of venous tonus may restore pelvic circulation and relieve pelvic symptomatology.

Aust N Z J Obstet Gynaecol. 2007 Aug;47(4):321-5.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces the size of experimental endometriosis in the rat model.

Aytan H, Caliskan AC, Demirturk F, Aytan P, Koseoglu DR.

Department of Obstetrics and Gynecology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey. drhakanaytan@yahoo.com

BACKGROUND: The effect of rosiglitazone, an activator of peroxisome proliferator-activated receptor-gamma, on the growth of ectopic uterine tissue was assessed. METHODS: Endometriosis was surgically induced in 28 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Four weeks later, rats were randomly grouped and a second laparatomy was performed. The length, width, height and volume of the explants were measured. Rosiglitazone at 0.2 mg/kg/day was orally administered to one group, while vehicle treatment was given to the control group. Four weeks later, rats were sacrificed and ectopic uterine tissues were re-evaluated morphologically and histologically. Scoring system was used to evaluate the preservation of epithelia. RESULTS: One rat in the study group and two rats in the control group died as a result of complications related to surgery. There was a significant difference in post-treatment length, width, height, and spherical volumes between control and rosiglitazone-treated groups. The epithelia were found to be preserved significantly better in the control group when compared with the rosiglitazone-treated group. CONCLUSION: Rosiglitazone was found to cause regression of experimental endometriosis in rats.

Curr Pharm Des. 2007;13(21):2118-28.

SRC inhibitors and angiogenesis.

Schenone S, Manetti F, Botta M.

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Genova, Italy. schensil@unige.it

Angiogenesis is a tightly regulated process that leads to the formation of new blood vessels in limited physiological conditions, and can also occur under pathological situations as retinopathies, arthritis, endometriosis and cancer. Enhanced angiogenesis is present in tumors that need new blood capillaries to grow, remove metabolic waste and transport the cells to locations distal to the primary tumor, facilitating metastasis formation. For these reasons, blockade of angiogenesis is an attractive approach for the treatment of both solid and haematological malignancies. Antiangiogenic therapy should be less toxic in comparison with conventional treatments such as chemotherapy, being angiogenesis a process relatively restricted to the growing tumor. The Src family of tyrosine kinases has been implicated in the intracellular signaling cascade that acts downstream of cell surface receptors to elicit different cellular functions, including growth, proliferation, adhesion and motility. Src kinases are frequently activated in human malignancies, causing tumor progression, metastasis formation and deregulating expression of proangiogenic molecules. This review reports several studies performed by different authors demonstrating the involvement of Src tyrosine kinases in angiogenesis by regulating different signalling pathways. Moreover, we report selective Src inhibitors for which a direct involvement with angiogenesis has been demonstrated, even if every Src inhibitor could potentially possesses also antiangiogenic properties. Biological data, structures and mechanisms of action of selected molecules, in terms of Src protein-inhibitor interactions, are also reported.

Am J Respir Crit Care Med. 2007 Nov 15;176(10):1048-53. Epub 2007 Jul 12.

Catamenial and noncatamenial, endometriosis-related or nonendometriosis-related pneumothorax referred for surgery.

Alifano M, Jablonski C, Kadiri H, Falcoz P, Gompel A, Camilleri-Broet S, Regnard JF.

Department of Thoracic Surgery, Hôtel-Dieu Hospital, Paris V University, Paris, France. marcoalifano@yahoo.com

RATIONALE: Catamenial and endometriosis-related pneumothorax are considered relatively rare entities. Their clinical characteristics and outcome are incompletely known. OBJECTIVES: To evaluate the frequencies, clinical characteristics, and outcomes of catamenial and endometriosis-related pneumothoraces occurring in women with no underlying lung disease referred for surgical treatment. METHODS: Clinical files of all the women of reproductive age referred to our center during a 6-year period for surgical treatment of spontaneous pneumothorax were retrospectively reviewed. Catamenial pneumothorax (CP) was defined as recurrent pneumothorax occurring between the day before and within 72 hours after the onset of menses. All histologic slides were reviewed to confirm initial diagnoses. MEASUREMENTS AND MAIN RESULTS: A total of 114 women underwent video-assisted thoracic surgery; 28 women (24.6%) had CP (right-sided in all but one), and diaphragmatic abnormalities (perforations and/or nodules) were observed in 22 of them. Diaphragmatic abnormalities were seen in 21 of 86 patients with non-CP. Histologic examination found endometriosis, mainly diaphragmatic, in 18 of 28 CPs and 11 of 86 non-CPs. A 6-month antigonadotropic treatment was prescribed postoperatively to women with either CP or endometriosis-related pneumothorax. Mean follow-up was 32.7 (+/-18.5) months. Recurrence rates in CP, non-CP but endometriosis-related, and non-CP non-endometriosis-related pneumothoraces were 32, 27, and 5.3%, respectively. CONCLUSIONS: Our experience shows that (1) CP and/or endometriosis-related pneumothoraces account for an important percentage of spontaneous pneumothoraces referred for surgery, (2) diaphragmatic abnormalities seem to play a fundamental role in their pathogenesis, and (3) management is difficult because of the high recurrence rate.

Curr Opin Obstet Gynecol. 2007 Aug;19(4):395-401.

The search for genetic variants predisposing women to endometriosis.

Di W, Guo SW.

Institute of Obstetric and Gynecologic Research, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai, China.

PURPOSE OF REVIEW: There is a growing interest in the search for genetic variants that predispose women to endometriosis, yet little headway has been made in the identification of such variants, and published studies are often conflicting. This review evaluates the evidence for a hereditary component in endometriosis, appraises the evidence of linkage and association of genetic polymorphisms and endometriosis, and discusses the implications of this reappraisal for clinical practice and research. RECENT FINDINGS: The familial aggregation of endometriosis appears to be established although most family studies suffer from various methodological deficiencies, such as failure to control for risk factors and the number of sisters that cases and controls have. The familial aggregation could also be attributed to familial aggregation of risk factors and/or some intermediatory traits that have genetic components. The published association studies are often conflicting, perhaps reflecting these uncertainties. SUMMARY: The search for genetic variants predisposing women to endometriosis has generated a lot of interest, and yet so far it has not shed much light on its pathogenesis. Further genetic epidemiological studies with more solid design and methodological rigor are needed.

Curr Opin Obstet Gynecol. 2007 Aug;19(4):319-24.

Management of ureteral endometriosis: areas of controversy.

Ghezzi F, Cromi A, Bergamini V, Bolis P.

Department of Obstetrics and Gynecology, University of Insubria, Varese, Italy. fabio.ghezzi@uninsubria.it

PURPOSE OF REVIEW: In this review we critically evaluate what we know and what we still do not know about pathogenesis, diagnosis and treatment of ureteral endometriosis, highlighting areas of controversy. RECENT FINDINGS: Recent studies have produced new insights into diagnostic and management options for ureteral endometriosis. SUMMARY: The diagnosis of ureteral endometriosis entails a high index of suspicion for the disorder. Imaging techniques are of limited value in providing an accurate depiction of extension of ureteral lesions. Preliminary results suggest that magnetic resonance urography is accurate in differentiating between intrinsic and extrinsic forms of ureteral involvement, but further studies are required to define its role in directing better treatment. Current controversies in the treatment of ureteral endometriosis are over whether segmental resection and anastomosis or ureterolysis are indicated, and whether minimal-access procedures are equally effective than their traditional open counterparts. Recent studies suggest that laparoscopic ureterolysis can be an effective treatment option in most patients with ureteral endometriosis but that recurrence rates are not negligible, as suggested in pioneering works. Successful application of laparoscopic surgery, even for procedures that have traditionally necessitated laparotomy, has been reported. Extensive experience with endourological techniques is prerequisite for success.

Curr Opin Obstet Gynecol. 2007 Aug;19(4):308-13.

Outcome of laparoscopic colorectal resection for endometriosis.

Daraï E, Bazot M, Rouzier R, Houry S, Dubernard G.

Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France. emile.darai@tnn.aphp.fr

PURPOSE OF REVIEW: Endometriosis is a frequent gynaecological disorder in young women. Colorectal endometriosis accounts for about 90% of all intestinal locations. The effectiveness of medical therapies is poor, and surgery, including colorectal resection, is therefore often required. Since the first description of laparoscopic colorectal resection by Redwine and Sharp, the feasibility of this approach has been confirmed by several teams but remains a matter of debate. RECENT FINDINGS: A review of the literature showed that conversion to laparotomy was necessary in 7.8% of cases. Segmental colorectal resection appears to be the best option, owing to the risk of incomplete resection in the case of full-thickness disc or superficial-thickness excision. However, complications are more frequent with segmental resection than with other procedures, and include de-novo urinary disorders. Laparoscopic colorectal resection for endometriosis is associated with symptom relief and a significant improvement in quality of life. In addition, 44.6% of women wishing to conceive were able to do so. SUMMARY: Laparoscopic colorectal resection for endometriosis appears to be an adequate alternative to laparotomy. Further studies are required to identify objective criteria with which to select women most likely to benefit from this surgery, which must be performed in special units.

Curr Opin Obstet Gynecol. 2007 Aug;19(4):303-7.

The value of two-step operative laparoscopy with interval pituitary suppression in the treatment of infertility caused by severe endometriosis.

Ball E, Byrne H, Davis C.

The Centre for Reproductive Medicine and Surgery, Kenton and Lucas Wing, St Bartholomew’s Hospital, London, UK.

PURPOSE OF REVIEW: To appraise a new approach to laparoscopic surgery for infertility caused by advanced endometriosis. RECENT FINDINGS: Endometriosis is a common systemic and local disease with altered peritoneal function, which requires both systemic and local treatment. Medication alone cannot improve infertility, and laparoscopic treatment, particularly in severe endometriosis, has a high recurrence rate and is often limited by technical difficulties. Novel treatment strategies have therefore to be sought, especially in women who do not want in-vitro fertilization as a first option, either because they suffer from pain in addition to infertility or want to enhance their fertility over many cycles. SUMMARY: Two-step operative laparoscopy with interval pituitary suppression by means of gonadotrophin-releasing hormone analogues reduces the extent of endometriosis, as classified by the American Fertility Association, and appears to be a promising method of achieving optimal cytoreduction and facilitating complicated surgery in severe endometriosis, while protecting the ovary from unnecessary trauma. A large-scale well-designed study is needed to confirm that this treatment leads to improved pregnancy rates.

Biol Reprod. 2007 Oct;77(4):681-7. Epub 2007 Jul 11.

Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis.

Xue Q, Lin Z, Cheng YH, Huang CC, Marsh E, Yin P, Milad MP, Confino E, Reierstad S, Innes J, Bulun SE.

Division of Reproductive Biology Research, Department of Obsterics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

Steroid receptors in the stromal cells of endometrium and its disease counterpart tissue endometriosis play critical physiologic roles. We found that mRNA and protein levels of estrogen receptor 2 (ESR2) were strikingly higher, whereas levels of estrogen receptor 1 (ESR1), total progesterone receptor (PGR), and progesterone receptor B (PGR B) were significantly lower in endometriotic versus endometrial stromal cells. Because ESR2 displayed the most striking levels of differential expression between endometriotic and endometrial cells, and the mechanisms for this difference are unknown, we tested the hypothesis that alteration in DNA methylation is a mechanism responsible for severely increased ESR2 mRNA levels in endometriotic cells. We identified a CpG island occupying the promoter region (-197/+359) of the ESR2 gene. Bisulfite sequencing of this region showed significantly higher methylation in primary endometrial cells (n = 8 subjects) versus endometriotic cells (n = 8 subjects). The demethylating agent 5-aza-2′-deoxycytidine significantly increased ESR2 mRNA levels in endometrial cells. Mechanistically, we employed serial deletion mutants of the ESR2 promoter fused to the luciferase reporter gene and transiently transfected into both endometriotic and endometrial cells. We demonstrated that the critical region (-197/+372) that confers promoter activity also bears the CpG island, and the activity of the ESR2 promoter was strongly inactivated by in vitro methylation. Taken together, methylation of a CpG island at the ESR2 promoter region is a primary mechanism responsible for differential expression of ESR2 in endometriosis and endometrium. These findings may be applied to a number of areas ranging from diagnosis to the treatment of endometriosis.

Prog Urol. 2007 May;17(3):381-4.

[Neurourological consequences of gynaecological surgery (endometriosis, simple hysterectomy, radical colpohysterectomy), colorectal surgery and pelvic radiotherapy]

[Article in French]

Vidart A, Mozer P, Chartier-Kastler E, Ruffion A.

Service d’urologie, GH Pitié Salpétrière, Paris VI, France. casodex@mac.com

Apart from damage to bladder innervation, a number of local diseases and treatments such as radiotherapy can induce lower urinary tract functional disorders. Some of these disorders can be treated according to the principles used in the management of neurogenic bladder The purpose of this review is to report the functional consequences of pelvic endometriosis, radiotherapy, colorectal surgery and urinary incontinence surgery with particular emphasis on situations in which a neurogenic mechanism is suspected.

Semin Immunopathol. 2007 Jun;29(2):193-210.

Neuroendocrine-immune disequilibrium and endometriosis: an interdisciplinary approach.

Tariverdian N, Theoharides TC, Siedentopf F, Gutiérrez G, Jeschke U, Rabinovich GA, Blois SM, Arck PC.

Center of Internal Medicine and Dermatology, Division of PsychoNeurolmmunology, Charité, University Medicine Berlin, Berlin, Germany.

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, proteinglycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis.

Arch Pathol Lab Med. 2007 Jul;131(7):1099-102.

Expression of p63 differs in peritoneal endometriosis, endometriomas, adenomyosis, rectovaginal septum endometriosis, and abdominal wall endometriosis.

Poli Neto OB, Ferreira HM, Ramalho LN, Rosa e Silva JC, Candido dos Reis FJ, Nogueira AA.

Department of Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. polineto@fmrp.usp.br

CONTEXT: Although there is evidence that endometriosis results from basal endometrium dislocation, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kDa membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract. OBJECTIVE: To determine whether p63 is expressed differently in peritoneal endometriosis, endometriomas, and adenomyosis, as well as in deep endometriotic nodules of the rectovaginal septum and abdominal wall. DESIGN: This study includes a prospective series of consecutive patients (Canadian Task Force classification II-2) from a tertiary care university hospital. Specimens collected from 83 patients (15 peritoneal endometriosis specimens, 22 endometrioma specimens, 36 adenomyosis specimens, and 10 rectovaginal septum/abdominal wall specimens) were evaluated. Diagnostic and operative laparoscopies or laparotomies were performed, and tissue samples were obtained. Immunohistochemistry was used to evaluate p63 expression. RESULTS: Positivity for p63 was detected in 93.3% of the peritoneal endometriosis specimens, 81.8% of the endometrioma specimens, 36.1% of the adenomyosis specimens, and none of the rectovaginal/abdominal wall endometriosis specimens (P < .001). Distribution of p63 immunostaining in the positive specimens was homogeneous. CONCLUSIONS: Endometriotic lesions express p63 differently, and some retain the basal/reserve cell immunophenotype. Nevertheless, it remains unclear whether the lack of p63 expression in some lesions is related to the extent of the disease, to its clinical behavior, or to exacerbation of the accompanying symptoms.

Histol Histopathol. 2007 Oct;22(10):1161-6.


Batt RE, Smith RA, Buck Louis GM, Martin DC, Chapron C, Koninckx PR, Yeh J.

Department of Gynecology-Obstetrics, University at Buffalo, State University of New York, Buffalo, New York 14222, USA. rbatt@buffalo.edu

Müllerianosis may be defined as an organoid structure of embryonic origin; a choristoma composed of müllerian rests–normal endometrium, normal endosalpinx, and normal endocervix–singly or in combination, incorporated within other normal organs during organogenesis. A choristoma is a mass of histologically normal tissue that is “not normally found in the organ or structure in which it is located” (Choristoma, 2006). Müllerian choristomas are a subset of non-müllerian choristomas found throughout the body. Histologically, endometrial-müllerianosis and endometriosis are both composed of endometrial glands and stroma, but there the similarity ends. Their pathogenesis is different. Sampson faced the same difficulty with pathogenesis and nomenclature when he wrote: “The nomenclature of misplaced endometrial or müllerian lesions is a difficult one to decide upon.” “The term müllerian would be inclusive and correct, but unfortunately it suggests an embryonic origin.” Sampson then divided “misplaced endometrial or müllerian tissue” into “four or possibly five groups, according to the manner in which this tissue reached its ectopic location” (Sampson, 1925). Sampson’s classification of heterotopic or misplaced endometrial tissue is based on pathogenesis: 1) “direct or primary endometriosis” [adenomyosis]; “a similar condition occurs in the wall of the tube from its invasion by the tubal mucosa” [endosalpingiosis]; 2) “peritoneal or implantation endometriosis;” 3) “transplantation endometriosis;” 4) “metastatic endometriosis;” and 5) “developmentally misplaced endometrial tissue. (I admit the possibility of such a condition, but have never been able to appreciate it.)” (Sampson, 1925). It is precisely this condition “developmentally misplaced endometrial tissue,” [müllerianosis] that is the subject of this review.

MMW Fortschr Med. 2007 Feb 22;149(8):21.

[Tumorous lesion in the sigmoid. Was it really a carcinoma?]

[Article in German]

Stiefelhagen P.

Acta Obstet Gynecol Scand. 2007;86(7):877-81.

Inflammatory markers in endometriosis: reduced peritoneal neutrophil response in minimal endometriosis.

Riley CF, Moen MH, Videm V.

Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Inflammation is considered to play a role in the pathogenesis of endometriosis. Inflammatory activation in endometriosis was tested based on the hypothesis that pain and endometriosis stage are related to the degree of local and systemic inflammation. Methods: Eighteen patients with endometriosis and 14 controls without endometriosis were studied. Cancer antigen 125 and C-reactive protein were analyzed in blood, and in aspirated peritoneal fluid, lactoferrin, myeloperoxidase (neutrophil granulocyte activation marker), sC5b-9 (terminal complement complex), soluble intercellular adhesion molecule 1 (marker for extent of endometriotic tissue), neopterin, and tumor necrosis factor alpha (monocyte/macrophage activation) were evaluated and related to pain, endometriosis stage, and clinical data. Results: None of the measured markers were different between control and endometriosis patients, or in women with or without menstrual pain, dyspareunia, or other types of pelvic pain. Lactoferrin and myeloperoxidase concentrations were significantly lower in patients with endometriosis stage I compared to control patients and endometriosis patients with stage III/IV disease. As expected, cancer antigen 125 concentrations were increased in endometriosis patients of stage III/IV. CONCLUSIONS: Neutrophil granulocytes in endometriosis patients may have a lowered ability to respond to weak activation signals, while in more extensive endometriosis stronger neutrophil activation may be related to a proinflammatory effect of endometriotic tissue.

Acta Obstet Gynecol Scand. 2007;86(7):855-60.

Success in intrauterine insemination: the role of etiology.

Ahinko-Hakamaa K, Huhtala H, Tinkanen H.

Department of Obstetrics and Gynaecology, Tampere University Hospital, Tampere, Finland. katja.ahinko-hakamaa@pshp.fi

BACKGROUND: We aimed to identify the prognostic factors for the highest pregnancy rate and lowest multiple pregnancy rate in different infertility etiology groups among women undergoing insemination treatment. METHODS: A total of 1,171 cycles among 532 infertile couples were retrospectively studied and the impact of different prognostic factors on pregnancy rate in five different etiology subgroups was analyzed. RESULTS: The pregnancy rate/cycle was highest (19.2%) among women with anovulatory infertility and lowest (11.9%) in endometriosis based infertility. Multiple pregnancy rate varied between 3.6% (male infertility) and 13.2% (anovulatory infertility). In unexplained infertility ovarian stimulation resulting in three follicles (pregnancy rate 24.2%) and inseminated motile sperm count >30×10(6) (pregnancy rate 19.8%) were significant prognostic factors. In anovulatory infertility stimulation with sequential clomiphene citrate and human menopausal gonadotrophin was a positive predictive factor, with a pregnancy rate of 36%. In male infertility stimulation with sequential clomiphene citrate/human menopausal gonadotrophin resulted in the best pregnancy rate (25.0%). In endometriosis-based infertility the pregnancy rate was best with clomiphene citrate stimulation (21.1%) and inseminated motile sperm count >30×10(6) (24.3%). In combined infertility the highest pregnancy rate was with sequential clomiphene citrate/human menopausal gonadotrophin stimulation and with three follicles (30%), and even 18.2% with inseminated motile sperm count <5.0×10(6). CONCLUSIONS: The etiology of the infertility is important when optimal insemination treatment is planned. The impact of the woman’s age, sperm count, stimulation protocol, and the follicle number on the pregnancy rate and multiple pregnancy rate is associated with the etiology of the infertility.

ANZ J Surg. 2007 Jul;77(7):562-71.

Rectal endometriosis: results of radical excision and review of published work.

Brouwer R, Woods RJ.

Department of Colorectal Surgery, St Vincent’s Hospital, Melbourne, Victoria, Australia.

BACKGROUND: The aim of this paper is to review the results of surgical excision of rectal endometriosis and review the published work on this challenging condition. METHODS: All cases of endometriosis involving the rectum treated by a single colorectal surgeon were identified from a prospective database and the results reviewed. RESULTS: Between 1995 and 2005, 213 rectal procedures were carried out on 203 patients together with an endogynaecologist. Eighteen cases involved dissection of endometriosis off the rectal wall, 58 involved full-thickness excision of the anterior rectal wall and 137 segmental excisions of the rectum were carried out. A loop ileostomy was required in 7 (5%) of the segmental resections. Seventy-five per cent of the cases were either laparoscopic or laparoscopically assisted. Infertility was significantly more common in the group requiring a segmental resection (P=0.026) and a history of rectal pain during defecation more common in patients having dissection of endometriosis off the rectal wall (P=0.031). There were no other significant differences between the different types of rectal surgery. The morbidity for all rectal procedures was 7% and there was one anastomotic leak in the segmental resection group. The actuarial rectal recurrence rate of endometriosis was 22.2% 95% confidence interval (CI) (2.5, 42.0) for dissection off the rectal wall and this was significantly different from the recurrence of 5.17% 95%CI (0.0, 10.9) for anterior rectal wall excision and 2.19% 95%CI (0.0, 4.6) for segmental rectal resection (P=0.007). The overall rectal recurrence for all cases was 4.69% 95%CI (1.8, 7.5). CONCLUSION: Endometriosis of the rectum can be successfully treated with low morbidity and low recurrence rates by excising the disease as completely as possible using full-thickness excision of the anterior rectal wall or segmental resection of the rectum.

Chin J Integr Med. 2007 Jun;13(2):109-14.

Expressions of VEGF and Ki-67 in eutopic endometrium of patients with endometriosis and effect of Quyu Jiedu Recipe on VEGF expression.

Lian F, Liu HP, Wang YX, Zhang JW, Sun ZG, Ma FM, Zhang N, Liu YH, Meng Q.

Reproduction Center, Affiliated Hospital of Shandong University of TCM, Jinan, 250011, China. f_lian@163.com

OBJECTIVE: To observe the clinical efficacy of Quyu Jiedu Recipe (, QJR) in treating endometriosis (EM), and to explore the levels of vascular endothelial growth factor (VEGF) and cell proliferative nucleoprotein antigen (Ki-67), their changes before and after treatment and the clinical significance in the trial. METHODS: Fifty patients of EM were randomly assigned to two groups. The 26 patients in the QJR group were treated with QJR, and the 24 patients in the gestrinone (GT) group with gestrinone. Besides, a normal control group with 20 healthy women was set up. The therapeutic effects in the two treated groups were compared. Expressions of VEGF and Ki-67 in eutopic endometrium of all subjects (with both patients and healthy women at the median secretive phase) were determined with immunohistochemical stain before treatment, and the determination in the two treated groups was repeated after 3-month treatment in the same phase. RESULTS: Before treatment, the VEGF and Ki-67 expression positive rates and their mean optic density (MOD) were higher in patients than in healthy women (P<0.05). After treatment, the positive rate and MOD of VEGF expression lowered significantly than before treatment (P<0.05), but those of Ki-67 changed insignificantly, and comparison between the two treated groups showed no significant difference (P>0.05). CONCLUSION: QJR could markedly improve the symptoms of menorrhagia and menstrual disorder, and its mechanism might be related with the lowering of eutopic endometrial VEGF expression. VEGF and Ki-67 show a high expression in eutopic endometrium of patients with EM.

J Vasc Interv Radiol. 2007 Jul;18(7):835-41.

Uterine artery embolization for symptomatic adenomyosis with or without uterine leiomyomas with the use of calibrated tris-acryl gelatin microspheres: midterm clinical and MR imaging follow-up.

Lohle PN, De Vries J, Klazen CA, Boekkooi PF, Vervest HA, Smeets AJ, Lampmann LE, Kroencke TJ.

Department of Radiology, St Elisabeth Ziekenhuis, Tilburg University, Tilburg, The Netherlands. radiol@knmg.nl

PURPOSE: To evaluate clinical and magnetic resonance (MR) imaging results after uterine artery embolization (UAE) in women with symptomatic adenomyosis with or without uterine leiomyomas. MATERIALS AND METHODS: Thirty-eight women with symptomatic adenomyosis with or without uterine leiomyomas were treated with UAE with calibrated tris-acryl gelatin microspheres. Based on MR findings, women were categorized as having pure adenomyosis (group A; n = 15), adenomyosis dominance with fibroid tumors (group B; n = 14), or fibroid tumor dominance with adenomyosis (group C; n = 9). RESULTS: Heavy menstrual bleeding, pain, and bulk-related symptoms at last follow-up at a median of 16.5 months (range, 3-38 months) were compared with baseline symptoms. With follow-up MR imaging at a median of 12 months (range, 3-36 months), changes in uterine volume, leiomyoma volume, junctional zone thickness, and contrast enhancement of adenomyosis were assessed. After embolization, adenomyosis infarction could be depicted on contrast medium-enhanced MR in 44.1% of cases. Median reductions of uterine volume, fibroid tumor volume, and junctional zone thickness were 44.8%, 77.1%, and 23.9%, respectively. In group A, three patients needed additional surgery after UAE, in addition to two in group B and one in group C. In the remaining 32 patients, except for one patient in group C, all preexisting symptoms (eg, bleeding, pain, bulk-related symptoms) improved or resolved after UAE. Overall, 84.2% of women were satisfied with the results of UAE. CONCLUSION: In this study, midterm results (at a median of 16.5 months) showed that UAE in symptomatic adenomyosis with or without uterine leiomyomas is effective. Hysterectomy was avoided in the vast majority of patients. MR imaging showed reduction of uterine volume and junctional zone thickness.

Hum Reprod. 2007 Sep;22(9):2494-500. Epub 2007 Jul 3.

Anticardiolipin antibody levels in women undergoing first in vitro fertilization/embryo transfer.

Caccavo D, Pellegrino NM, Lorusso F, Capotorto M, Vacca M, Vimercati A, Depalo R.

Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy. caccavo@midim.uniba.it

BACKGROUND: The clinical relevance of antiphospholipid antibodies (aPL) in women undergoing in vitro fertilization/embryo transfer (IVF/ET) and the role of IVF treatment in affecting antiphospholipid levels are controversial. The aim of this study was to evaluate anticardiolipin antibody (aCL) levels and the effect of IVF treatment on aCL in women undergoing their first IVF/ET cycle. METHODS: Immunoglobulin G (IgG)- and IgM-aCL were determined by enzyme-linked immunosorbent assay in 50 women undergoing IVF/ET, 18 due to endometriosis, 16 to tubal factor (TF) and 16 to male factor, before starting treatment (T0), on the day of oocyte retrieval (T1) and 14 days after ET (T2). A group of 31 age-matched fertile women served as controls. RESULTS: aCL levels detected at T0 in patients were not significantly different compared with the control group. IgG- but not IgM-aCL significantly increased at T2 in comparison with T0 (P < 0.001) and T1 (P < 0.05). The difference between T2 and T0 reached statistical significance in patients with endometriosis (P = 0.003) or TF (P = 0.018). No relationship was found between aCL and pregnancy. CONCLUSIONS: Our results indicate that IVF treatment increases IgG-aCL levels in patients with endometriosis and TF, but their presence seems to have no clinical relevance.

Hum Reprod. 2007 Aug;22(8):2120-7. Epub 2007 Jul 3.

Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems.

Gilabert-Estellés J, Ramón LA, España F, Gilabert J, Vila V, Réganon E, Castelló R, Chirivella M, Estellés A.

Gynecology Service, Hospital Arnau de Vilanova, Valencia, Spain.

BACKGROUND: Endometriosis is a highly prevalent, benign disease in which the angiogenic, fibrinolytic and metalloproteinase (MMP) systems may be implicated. The objective of this study is to analyse mRNA expression and protein levels of several angiogenic factors and to correlate them with several components of the fibrinolytic and MMP systems in samples from 71 women with endometriosis and 50 controls. METHODS AND RESULTS: Eutopic endometrium showed higher mRNA expression of vascular endothelial growth factor (VEGF) in patients than in controls. However, ovarian endometrioma had lower VEGF mRNA levels than did the eutopic endometrium of patients. Similar results were obtained for VEGF protein levels. On the other hand, a significant increase in thrombospondin-1 (TSP-1) levels was observed in ovarian endometrioma than in eutopic endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in VEGF, urokinase-type plasminogen activator (uPA) and MMP-3 levels than that of controls. A significant correlation was observed between the levels of VEGF and uPA in endometrium and in peritoneal fluid. CONCLUSIONS: Endometrium and peritoneal fluid from women with endometriosis have increased levels of VEGF, uPA and MMP-3 levels. Therefore, the development of endometriotic implants at ectopic sites may be facilitated, promoting the progress of the endometriosis.

J Fam Plann Reprod Health Care. 2007 Jul;33(3):189-93.

Endometriosis-associated dyspareunia: the impact on women’s lives.

Denny E, Mann CH.

Faculty of Health, University of Central England, Birmingham, UK. elaine.denny@uce.ac.k

BACKGROUND AND METHODOLOGY: Endometriosis is a chronic condition in which endometrial glands and stroma are present outside of the uterus. Whereas chronic pelvic pain is the most commonly experienced pain of endometriosis, many women also suffer from deep dyspareunia. In order to determine how much of an impact endometriosis-associated dyspareunia has on the lives and relationships of women a qualitative study using semi-structured interviews, supplemented with quantitative data on the extent of dyspareunia, was conducted in a dedicated endometriosis clinic in the West Midlands, UK with 30 women aged from 19 to 44 years. RESULTS: The main outcome measures were the extent of dyspareunia within the sample of women, and the impact of dyspareunia on quality of life. The experience of dyspareunia was found to be higher than in previous research. Three main themes emerged. The experience of pain was found to limit sexual activity for the majority of the sample, with a minority ceasing to be sexually active. Lack of sexual activity resulted in a lowering of self-esteem and a negative effect on relationships with partners, although the experience differed between younger and older women. DISCUSSION AND CONCLUSIONS: The experience of dyspareunia is a significant factor in the quality of life and relationships for women living with endometriosis. For most of the women in the study it was very severe and resulted in their reducing or curtailing sexual activity. Qualitative research can produce salient data that highlight the impact of dyspareunia on self-esteem and sexual relationships.

Int J Gynaecol Obstet. 2007 Oct;99(1):33-7. Epub 2007 Jun 28.

Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis.

Pupo-Nogueira A, de Oliveira RM, Petta CA, Podgaec S, Dias JA Jr, Abrao MS.

Endometriosis Unit, Department of Obstetrics and Gynaecology, School of Medicine, Universidade de São Paulo (FMUSP-SP), São Paulo, Brazil.

OBJECTIVES: To investigate whether there is an association between vascular endothelial growth factor (VEGF) levels in serum and peritoneal fluid, and the presence of pelvic endometriosis and its clinical symptoms. METHODS: Blood and peritoneal fluid sample levels of VEGF were measured in 46 women undergoing laparoscopy: 32 with suspected endometriosis and 14 with confirmed endometriosis. Data were analyzed according to phase of the menstrual cycle, symptoms, disease stage, and disease site. RESULTS: There were no significant associations between serum and peritoneal fluid levels of VEGF and the presence of endometriosis, even when controlling for the menstrual phase. However, among the women with confirmed endometriosis, there was a significant increase (P=0.002) in the mean peritoneal VEGF level in those in the late secretory phase compared with those in the proliferative and early secretory phases. CONCLUSIONS: Measuring VEGF levels in symptomatic patients is not helpful to differentiate those with endometriosis from those with a different condition. However, in the late secretory and menstrual phases, mean VEGF levels were higher in women with confirmed endometriosis than in those suspected of having the disease.

Fertil Steril. 2007 Aug;88(2):534; author reply 534-5. Epub 2007 Jun 28.

Comment on:

Fertil Steril. 2007 Feb;87(2):362-6.

Endometriomas–more careful examination in vivo and communication with the pathologist.

Brosens IA, Puttemans P, Campo R, Gordts S, Gordts S.

Cephalalgia. 2007 Jun;27(6):563-5.

Bath-related headache: a case report.

Tanaka M, Okamoto K.

Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. tanakama@showa.unma-u.ac.jp

Pediatr Pulmonol. 2007 Aug;42(8):746.

Comment in:

Pediatr Pulmonol. 2007 Sep;42(9):854.

Comment on:

Pediatr Pulmonol. 2007 Apr;42(4):386-8.

CD10 in the cytological diagnosis of endobronchial endometriosis.

Ferrero S, Ragni N, Remorgida V, Arena E.

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