HPB Surg. 2009;2009:407206. Epub 2009 Jul 5.

Case hepatic endometriosis: a continuing diagnostic dilemma.

Goldsmith PJ, Ahmad N, Dasgupta D, Campbell J, Guthrie JA, Lodge JP.

Hepatobiliary and Transplant Unit, St James’s University Hospital, Leeds LS9 7TF, UK. peter.lodge@leedsth.nhs.uk

BACKGROUND: Intraparenchymal endometriosis of liver is rare. It may present as liver tumour and the diagnosis is not usually established till after surgery. CASE OUTLINE: A 48-year-old postmenopausal woman presented with right upper quadrant pain and a cystic liver mass. Liver function tests and tumour markers (alphaFP, CEA, CA 19-9, and CA 125) were normal. Radiological imaging (USS, CT and MRI) suggested a thick walled cystic mass involving segments IV and VIII with complex intracystic septations. Frozen section at operation suggested a benign cystadenoma. The cyst was enucleated using a CUSA (Cavitron ultrasonic aspirator). The final histology confirmed endometriosis. DISCUSSION: Eleven cases of hepatic endometrioma have been reported and only four in postmenopausal women. Preoperative diagnosis poses a challenge and so far none of the cases have been diagnosed preoperatively. Surgery remains the treatment of choice. Accurate diagnosis at time of operation may avoid extensive liver surgery and its associated morbidity.

Yi Chuan. 2009 May;31(5):479-84.

 

Relationship between IL-10 promoter gene polymorphisms and the susceptibility to endometriosis

[Article in Chinese]

He P, Zhang XM, Deng L, Ma JY.

The Obstetrics and Gynecology Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China. heipei2@sina.com

The purpose of this study was to investigate the relationship between IL-10 promoter gene polymorphism and the susceptibility to endometriosis (EMs) in Chinese population. Amplification refractory mutation system polymerase chain reactions (ARMS-PCR) and DNA sequencing were performed to detect polymorphism of -1082G/A site and PCR-RFLP was used to determine the genotypes in -819T/C and -592A/C sites. One hundred and nineteen Chinese women with different stage EMs and 120 controls were employed in this study. Although there were no significant differences in the polymorphism of -1082 site between two groups (P>0.05), the frequencies of -819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were significantly increased in EMs patients compared with the controls (P<0.05). The frequencies of -819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were significantly increased in III-IV EMs patients compared with I-IIMs or controls (P<0.01). This suggests that polymorphisms of IL-10-819 (T/C) and -592 (A/C) may be associated with the susceptibility to EMs in Chinese population.

Arch Gynecol Obstet. 2009 Jul 8. [Epub ahead of print]

Different HLA-DR expression in endometriotic and adenomyotic lesions: correlation with transvaginal ultrasonography findings.

Koumantakis EE, Panayiotides JG, Goumenou AG, Ziogos EC, Margariti A, Kalapothaki V, Matalliotakis IM.

Department of Radiology, NIMITS Hospital, Athens, Greece.

OBJECTIVE: Human leukocyte antigen-DR (HLA-DR) has been implicated in eutopic and ectopic glandular epithelial cells in endometriosis. We investigated the expression of HLA-DR in endometriotic and adenomyotic tissues within the stromal and glandular cells. Moreover, we correlate the HLA-DR expression according the transvaginal ultrasonography findings. METHODS: We studied operative and pathologic reports of 113 women who underwent laparoscopic or laparotomy treatment of endometrioma or adenomyosis. Tissues from 51 women with endometrioma and 62 women with adenomyosis were retrospectively evaluated. The distribution and intensity of the HLA-DR immunostaining was assessed using electron microscopy. Pathologic finding of the uterine junction zone and the size of endometrioma were evaluated with the laparoscopic results and the ultrasound findings. RESULTS: In adenomyosis tissues, the percentage of HLA-DR cells expression was significantly higher in stromal cells (83.9%) compared to glandular cells (25.8%), (p < 0.001). The number of HLA-DR-positive endometriotic glandular cells was significantly higher than the total glandular adenomyotic cells (p < 0.005). HLA-DR-positive cells was significantly different between stromal (p < 0.016) and glandular cells (p < 0.044) in each side of endometrioma. Finally, HLA-DR-positive percentage cells were significantly more frequent in the secretory phase than the proliferative in stromal and glandular cells in both groups. CONCLUSION: HLA-DR antigen expression in endometrium and adenomyotic tissues. However, HLA-DR expression is distributed preferentially in glandular epithelial cells in endometrioma and in the adenomyotic stroma. In both groups the HLA-DR expression was significantly higher in the secretory phase than the proliferative or glandular and stroma cells. Larger perspective studies are needed to establish the expression of HLA antigens in immune reactions which occur in adenomyosis and endometriosis.

Arch Gynecol Obstet. 2009 Jul 8. [Epub ahead of print]

Post-hysterectomy menstruation: a rare phenomenon.

Lyngdoh BT, Kriplani A, Garg P, Maheshwari D, Bansal R.

Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India, basillyngdoh@gmail.com.

Post-menopausal bleeding is a common problem with varied etiology in the age group between 50 and 60 years. It is more likely to be of some pathologic cause which needs to be ruled out. Bleeding in a patient after hysterectomy is even rarer with varied causes like atrophic vaginitis, cervical stump cancer, infiltrating ovarian tumors, estrogen secreting tumors in other parts of the body. Endometriosis of the vault sometimes can cause post-menopausal bleeding. Diverticulitis of the bowel may give rise to vaginal discharge due to fistula, but bleeding is rare. Bladder pathology may cause vaginal bleeding. Our case is a rare case of vault endometriosis and should always be kept as a differential diagnosis in patients with bleeding after hysterectomy.

Radiology. 2009 Oct;253(1):126-34. Epub 2009 Jul 7.

Endometriosis: contribution of 3.0-T pelvic MR imaging in preoperative assessment–initial results.

Hottat N, Larrousse C, Anaf V, Noël JC, Matos C, Absil J, Metens T.

Departments of Radiology, Erasme Hospital, Université Libre de Bruxelles, B-1070 Brussels, Belgium. nhottat@ulb.ac.be

PURPOSE: To determine the accuracy of 3.0-T pelvic magnetic resonance (MR) imaging in the preoperative assessment of endometriosis and to evaluate colon wall involvement after intrarectal gel administration. MATERIALS AND METHODS: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Forty-one consecutive patients with clinical suspicion of endometriosis underwent pelvic MR imaging at 3.0 T before surgery. Single-shot and high-spatial-resolution axial T2-weighted, sagittal fat-suppressed T2-weighted, and axial fat-suppressed T1-weighted sequences were performed. T2-weighted sequences were repeated after the rectum was filled with ultrasonographic (US) gel. Two blinded readers interpreted images independently. Image quality was scored by using a four-point scale. Detailed mapping of deep endometriosis was performed. Colon wall infiltration was graded (none, serosa, muscularis, submucosa, mucosa). MR imaging results were compared with surgical and pathologic findings. Interobserver agreement was assessed by using kappa statistics. Nonparametric tests were performed to compare colon wall infiltration scores without and those with US gel and between observers. RESULTS: Twenty-seven of 41 patients had deep endometriosis at surgery and histopathologic examination. Sensitivity, specificity, positive and negative predictive values, and accuracy for the diagnosis of deep endometriosis at MR imaging were 96.3% (26 of 27), 100% (14 of 14), 100% (26 of 26), 93.3% (14 of 15), and 97.6% (40 of 41), respectively. kappa Values ranged from 0.65 to 1.0, depending on the location of deep endometriosis. Colon wall infiltration assessment by both readers correlated well with pathologic findings (Spearman coefficient, >0.93), although median wall involvement scores were lower at pathologic examination than for both readers both before (P = .042 and P = .011) and after (P = .079 and P = .011) intrarectal gel filling. CONCLUSION: MR imaging of the pelvis at 3.0 T is accurate in the diagnosis and staging of deep endometriosis for the preoperative assessment of patients clinically suspected of having endometriosis.

Bull Soc Pathol Exot. 2009 May;102(2):81-4.

Diagnosis of a cutaneous endometriosis decidualised and fistualized during pregnancy

[Article in French]

Millogo-Traoré F, Sanou-Lamien AM, Niamba P, Zanre Y, Bonkoungou G.

Service de gynecologie et d’obstétrique du CHU Yalgado-Ouédroaogo, Ouagadougou, BP 349 Ouagadougou 09, Burkina Faso. fmillogo_traore@caramail.com

A case of a decidualized and fistulized cutaneous endometriosis has been observed in the obstretrical and gynecological department of the Yalgado-Ouédraogo national hospital. The patient was a 3-year-old pregnant woman in her third pregnancy primipara, without any surviving child, who presented with a large scabby exulcerated plaque on an hyperpigmented lesion, associated with para umbilical. The patient underwent 12 years earlier a laparotomy for peritonitis worsened with parietal suppuration, then by rupture. The lesion has made the diagnosis difficult and the histologist concluded that it was a decidualised cutaneous endometriosis. Based on this observation, the first one until now, the authors have made a publication on the case.

Fertil Steril. 2009 Jul 4. [Epub ahead of print]

Fenofibrate causes regression of endometriotic implants: a rat model.

Onalan G, Zeyneloglu HB, Bayraktar N.

Obstetrics and Gynecology, Baskent University School of Medicine, Ankara, Turkey.

Fenofibrate -a peroxisome proliferator-activated receptor-a agonist- is an angiostatic agent that is commonly used in human liver diseases, therefore it may interfere with the angiogenetic process required for endometriosis. In a rat endometriosis model, we demonstrated that peritoneal implant areas and vascular endothelial growth factor levels in the peritoneal flud were significantly decreased in high dose or low dose finofibrate and luprolide acetate treated groups compared to control.

Oncol Rep. 2009 Aug;22(2):233-40.

Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review).

Kobayashi H, Kajiwara H, Kanayama S, Yamada Y, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sakata M, Sado T, Oi H.

Department of Obstetrics and Gynecology, Nara Medical University, Kashihara 634-8522, Japan. hirokoba@naramed-u.ac.jp

Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by iron-dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress.

J Pediatr Adolesc Gynecol. 2009 Oct;22(5):e159-62. Epub 2009 Jul 3.

Successful pregnancy following surgery in the obstructed uterus in a uterus didelphys with unilateral distal vaginal agenesis and ipsilateral renal agenesis: case report and literature review.

Altchek A, Paciuc J.

Mount Sinai School of Medicine and Hospital, Lenox Hill Hospital, New York, NY, USA. albertaltchek@aol.com

SYNOPSIS: After surgical correction of unilateral distal vaginal agenesis, the obstructed didelphic uterus was able to harbor 2 subsequent pregnancies. BACKGROUND: There was a congenital anomaly syndrome of uterus didelphys, unilateral distal vaginal aplasia, and ipsilateral renal aplasia. Intuition suggests that later pregnancy would be in the unobstructed uterus. OBJECTIVE: The purpose is to report pregnancy occurring twice in a previously obstructed didelphic uterus after surgical correction. CASE: A girl aged 13 years, 8 months presented with the syndrome of didelphic uterus, upper right hematocolpos, and right renal aplasia. Right vaginal marsupialization was done. Subsequently, she had 2 pregnancies in the right didelphic uterus. CONCLUSION: Pregnancy occurred in the obstructed uterus despite a large hematometra, extensive right pelvic peritoneal endometriosis, and hematocolpos. The surgeon should make every effort to preserve the obstructed uterus.

Colorectal Dis. 2009 Jul 3. [Epub ahead of print]

Laparoscopic Excision of Rectovaginal Endometriosis: Report of a prospective study and review of the literature.

Maytham G, Dowson H, Levy B, Kent A, Rockall T.

. Minimal Access Therapy Training Unit (MATTU), Post-Graduate Medical School, University of Surrey, Manor Park, Guildford, GU2 7WG.

Aims: The surgical management of rectovaginal endometriosis is challenging. We present our experience of the laparoscopic management of these difficult cases, together with a review of the current literature. Methods: A prospective database was established for all patients undergoing surgery for Deep Infiltrating Endometriosis (DIE) with rectovaginal and/or ureteric and bladder nodules. Outcomes analysed include operation performed, conversion and complication rates, and length of stay. These outcomes were compared with other laparoscopic rectal resections for alternative diagnoses recorded in the database and with outcomes seen in a literature review of studies on the surgical management of endometriosis. Results: Between April 2004 and November 2007, 54 patients underwent laparoscopic excision of rectovaginal endometriosis by a combined colorectal and gynaecological surgical team. 37% of patients underwent a rectal wall shave, 13% had a disc excision of the rectal wall, and 50% underwent segmental resection. There was a conversion rate of 4%, median duration of stay was 3 days, with 2% requiring transfusion. Major complications occurred in 7% of patients, with 4% requiring reoperation. Patients undergoing segmental resection for endometriosis had a higher complication rate than those having surgery for other diagnoses. There was an increased incidence of anastomotic stenosis, with histopathological results suggesting the disease process may contribute to this occurrence. Conclusions: Laparoscopic resection of rectovaginal endometriosis may be associated with a higher incidence of complications than resections performed for other diagnoses. Patients should be made aware of this risk, and the treatment of this condition should be undertaken in units with necessary experience.

Am J Pathol. 2009 Aug;175(2):547-56. Epub 2009 Jul 2.

Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease.

Bacci M, Capobianco A, Monno A, Cottone L, Di Puppo F, Camisa B, Mariani M, Brignole C, Ponzoni M, Ferrari S, Panina-Bordignon P, Manfredi AA, Rovere-Querini P.

Istituto Scientifico Ospedale San Raffaele, DIBIT, 3A1, via Olgettina 58, 20132, Milano Italy.

The mechanisms that sustain endometrial tissues at ectopic sites in patients with endometriosis are poorly understood. Various leukocytes, including macrophages, infiltrate endometriotic lesions. In this study, we depleted mouse macrophages by means of either clodronate liposomes or monoclonal antibodies before the injection of syngeneic endometrial tissue. In the absence of macrophages, tissue fragments adhered and implanted into the peritoneal wall, but endometriotic lesions failed to organize and develop. When we depleted macrophages after the establishment of endometriotic lesions, blood vessels failed to reach the inner layers of the lesions, which stopped growing. Macrophages from patients with endometriosis and experimental mice, but not nonendometriotic patients who underwent surgery for uterine leiomyomas or control mice, expressed markers of alternative activation. These markers included high levels of scavenger receptors, CD163 and CD206, which are involved in both the scavenging of hemoglobin with iron transfer into macrophages and the silent clearance of inflammatory molecules. Macrophages in both inflammatory liquid and ectopic lesions were equally polarized, suggesting a critical role of environmental cues in the peritoneal cavity. Adoptively transferred, alternatively activated macrophages dramatically enhanced endometriotic lesion growth in mice. Inflammatory macrophages effectively protected mice from endometriosis. Therefore, endogenous macrophages involved in tissue remodeling appear as players in the natural history of endometriosis, required for effective vascularization and ectopic lesion growth.

Hum Reprod. 2009 Oct;24(10):2504-14. Epub 2009 Jul 2.

Medical treatment for rectovaginal endometriosis: what is the evidence?

Vercellini P, Crosignani PG, Somigliana E, Berlanda N, Barbara G, Fedele L.

Department of Obstetrics and Gynaecology, Istituto Luigi Mangiagalli, University of Milan, Via Commenda 12, 20122 Milan, Italy. paolo.vercellini@unimi.it

BACKGROUND: Rectovaginal endometriosis usually causes distressing pain. Surgical treatment may be effective but is associated with a high risk of morbidity and major complications. Information on the effect of medical alternatives for pain relief in this condition is scarce. METHODS: A comprehensive literature search was conducted to identify all the English language published observational and randomized studies evaluating the efficacy of medical treatments on pain associated with rectovaginal endometriosis. A combination of keywords was used to identify relevant citations in PubMed, MEDLINE and EMBASE. RESULTS: A total of 217 cases of medically treated rectovaginal endometriosis were found; 68 in five observational, non-comparative studies, 59 in one patient preference cohort study, and 90 in a randomized controlled trial. An aromatase inhibitor was used in two of the non-comparative studies, vaginal danazol in one, a GnRH agonist in one, and an intrauterine progestin in one. Two estrogen-progestin combinations used transvaginally or transdermally were evaluated in the patient preference study, whereas an oral progestin and an estrogen-progestin combination were compared in the randomized controlled trial. With the exception of an aromatase inhibitor used alone, the antalgic effect of the considered medical therapies was high for the entire treatment period (from 6 to 12 months), with 60-90% of patients reporting considerable reduction or complete relief from pain symptoms. CONCLUSIONS: Despite problems in interpretation of data, the effect of medical treatment in terms of pain relief in women with rectovaginal endometriosis appear substantial.

J Minim Invasive Gynecol. 2009 Jul-Aug;16(4):510-2.
Uterine vein rupture at delivery as a delayed consequence of laparoscopic surgery for endometriosis: a case report.

Wada S, Yoshiyuki F, Fujino T, Sato C.

Teine Keijinkai Hospital, Department of Obstetrics & Gynecology, Teine-ku, Sapporo, Japan. wa_shin_2002@yahoo.co.jp

Laparoscopic resection of deep infiltrating endometriosis (DIE) has been reported to be an effective method for reduction of endometriosis-associated pain. As its complications, bowel perforation, urinary tract injury and neurogenic bladder are well known; however, uterine vein rupture during pregnancy has not been reported previously. We encountered a case of hemoperitoneum resulting from uterine vein rupture at a delivery as a delayed consequence of laparoscopic resection of DIE. A 31-year-old, para 2 woman underwent laparoscopic resection of lateral pelvic peritoneum, uterosacral ligaments, and bilateral endometriomas, exposing uterine vessels, which we covered with fibrin glue. Endometriosis-associated pain disappeared, and then the patient conceived 4 months later. The course of pregnancy and induction of labor with controlled oxytocin infusion was uneventful, and the patient delivered a female baby without asphyxia. Immediately after delivery, low abdominal pain with hypotension occurred despite absence of abnormal vaginal bleeding. Ultrasonography and the blood hemoglobin value suggested hemorrhagic shock owing to hemoperitoneum; therefore emergency exploratory laparotomy was performed. Active bleeding was found at the right uterine vein, which was then sutured for hemostasis. The patient received a blood transfusion and recovered without any problems. The bleeding lesion was located at the vein on which the peritoneum had been removed at the first laparoscopy, which suggested that the operation for DIE included a risk of uterine vessel rupture during pregnancy.

J Minim Invasive Gynecol. 2009 Jul-Aug;16(4):472-9.

Should the gynecologist perform laparoscopic bowel resection to treat endometriosis? Results over 7 years in 168 patients.

Pereira RM, Zanatta A, Preti CD, de Paula FJ, da Motta EL, Serafini PC.

Huntington Reproductive Medicine Centre, São Paulo, Brazil. ricardopereiramd@gmail.com

STUDY OBJECTIVE: To assess the feasibility and safety of laparoscopic bowel resections for endometriosis performed by gynecologic surgeons. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-3). SETTING: Fertility and pelvic surgery clinics. PATIENTS: One hundred sixty-eight women (age 21-53 years) with symptoms including pelvic pain, infertility, or both with 252 bowel endometriotic lesions underwent laparoscopic bowel resection performed by gynecologic surgeons between May 2000 and January 2008. INTERVENTIONS: Laparoscopic procedures for excision of several endometriotic nodes and lesions included shaving resection (LscShR), discoid resection (LscDR), segmental resection (LscSgR), terminal ileal resection (LscIR), partial cecal resection (LscCR), and appendectomy (LscAp). MEASUREMENTS AND MAIN RESULTS: The 168 patients underwent 172 laparoscopic bowel resections (4 patients were operated on twice) by the same surgeon. Lesions were distributed as follows: 133 (79%) in the rectum, 61 (24%) in the sigmoid colon, 47 (19%) in the appendix, 5 (2%) in the terminal ileum, 3 (1%) in the descending colon, and 3 (1%) in the cecum. At surgeon discretion, 12 lesions were not resected. A total of 216 bowel procedures were necessary to remove the 240 lesions include shaving resection in 22 patients (10%), discoid resection in 52 (24%), segmental resection in 92 (42%), terminal ileal resection in 2 (1%), partial cecal resection in 1 (0.6), and appendectomy in 47 (22%). Major complications occurred in 13 patients (7.6%) and included rectovaginal fistula in 3 patients (1.7%), rectosigmoid anastomosis dehiscence and bowel occlusion in 1 patient each (0.6%), and persistent bowel dysfunction in 4 patients (2.3%). These results are comparable to those reported in the literature to date. Complete relief of symptoms (measured using the Visick scale) was noted in patients with dysmenorrhea (59%), dyspareunia (75%), noncyclic pelvic pain (90%), pain on defecation (100%), constipation (83%), and cyclic rectal bleeding (100%). CONCLUSION: Surgery to treat bowel endometriosis can be safely and efficiently performed by the gynecologic pelvic surgeon. Meticulous training and a multidisciplinary approach to comprehensive operative care are necessary. These findings can be validated by prospective collaborative studies and reports from other surgeons.

Zhonghua Bing Li Xue Za Zhi. 2009 Feb;38(2):106-9.

Analysis of diagnosis accuracy of frozen sections in 73 cases of borderline tumor of ovary.

[Article in Chinese]

Li M, Liu YH, Zhuang HG, Lin HH, Zeng RH, Wang XB, Mei P, Luo DL, Luo XL, Zhang W.

Department of Pathology, Guangdong Provincial People’s Hospital, Guangzhou 510080, China.

OBJECTIVE: To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of the borderline tumor of ovary (BTO). METHODS: A retrospective analysis and comparison were done respectively between the accuracies of diagnoses made by using frozen and paraffin sections from the same tissue blocks for BTO from March 1995 to May 2008 achieved in the Department of Pathology, Guangdong General Hospital. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis. RESULTS: Of the 73 patients analyzed, 39 cases (53.42%) were histologically serous tumors, 32 (43.84%) were mucinous and 2 (2.74%) were endometrioid tumors. Diagnoses identical in those made by using either frozen or routine paraffin sections were 55/73 (75.34%). The sensitivity and positive predictive value of frozen section diagnosis were 87.30% and 85.94%, respectively. Underdiagnosis of frozen section were 18/73 (24.66%). There was no overdiagnosis cases obtained. Univariate analysis showed that tumor diameter and tumor histology were the predictors of underdiagnosis in frozen section analysis. And in multivariate analysis, only tumor diameter, rather than patient age, tumor histology and stage, bilateral side tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis. CONCLUSIONS: Intraoperative frozen section diagnosis of BTO has a low sensitivity and PPV. Underdiagnosis is not uncommon. Surgical management based on intraoperative frozen section diagnosis should be used with caution.

Zhonghua Fu Chan Ke Za Zhi. 2009 May;44(5):333-6.

Correlation between pelvic adhesions and pain symptoms of endometriosis

[Article in Chinese]

Hao M, Zhao WH, Wang YH.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan 030001, China. haomin865@hotmail.com

OBJECTIVE: To study the incidence of pelvic adhesions in endometriosis (EM) and the relationship between pelvic adhesions and pain symptoms. METHODS: The incidence of pelvic adhesions, dysmenorrhea, chronic pelvic pain, dyspareunia, dyschizia in 480 patients with EM were studied retrospectively to evaluate the correlation between pelvic adhesions and the degree of pain symptoms. In accordance with the revised American Fertility Society classification (r-AFS), it was observed that 155 cases were in Stage I, 33 cases were in stage II, 108 cases were in stage III and 184 were cases in stage IV. RESULTS: (1) Among 480 cases with EM, 72.3% (347/480) of patients have pelvic adhesions simultaneously, of which 25.2% (39/155) patients were in Stage I, 78.8% (26/33) patients were in Stage II, 90.7% (98/108) patients were in Stage III and 100.0% (184/184) patients were in Stage IV. It was found that positive correlation existed between the degree of pelvic adhesions and clinical staging of EM (r(s) = 0.870, P < 0.01). (2) 61.0% (293/480) of patients presented dysmenorrhoea, of which the percentages of mild, moderate and severe dysmenorrhea were 52.2% (153/293), 26.6% (78/293), 21.2% (62/293), respectively. The rate of patients presenting chronic pelvic pain (CPP), dyspareunia and dyschezia were 23.8% (114/480), 15.4% (74/480) and 7.1% (34/480), respectively. (3) Ovarian adhesions was positively correlated with dysmenorrhea and CPP (r(s) = 0.367 and 0.267, P < 0.01). Adhesion of the bottom and posterior wall of uterus was positively correlated with dysmenorrhea and CPP (r(s) = 0.336, 0.164, P < 0.01); adhesions of fallopian tubes were positively correlated with dysmenorrhea, CPP and dyschezia (r(s) = 0.283, 0.225 and 0.159, P < 0.01). Adhesions of rectum was positively correlated with dysmenorrhea (r(s) = 0.101, P < 0.05). In addition to dyspareunia, the degree of pelvic adhesions was positively correlated with dysmenorrhea, CPP and dyschezia (r(s) = 0.470, 0.273, 0.132, P < 0.01). CONCLUSION: Pelvic adhesions are characteristic lesions of endometriosis, the site and degree pelvic adhesions are closely correlated with pain symptoms.

Zhonghua Fu Chan Ke Za Zhi. 2009 May;44(5):328-32.

Study on incidence and associated factors of different degree endometrioma adhesions

[Article in Chinese]

Li XY, Leng JH, Lang JH, Dai Y, Wang YY.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.

OBJECTIVE: To investigate the relationship between degree of endometrioma adhesions and clinical feature, surgical treatment and postoperative recurrence. METHODS: From Jan 2003 to Mar 2008, 662 patients with endometrioma undergoing laparoscopic ovarian endometrioma excision in Peking Union Medical College Hospital were studied retrospectively. All patients were classified into four groups according to the extent of adhesions: 31 cases in none adhesions group, 123 cases in mild adhesions group (filmy thickness, avascular, easily separated adhesions), 310 cases in moderate adhesions group (less than a half of ovary was adjacent to dense thickness adhesions which was difficult to separate, or above a half of ovary were adjacent to filmy thickness adhesions) and 198 cases in severe adhesions group (above a half of ovary was adjacent to dense thickness, well vascularized adhesions which was difficult to separate, and always involved the other pelvic organs, observed angiogenesis). The comparison of degree, characteristics, period of pain, lab test, surgical management and postoperative recurrence was performed among those above groups. In the mean time, risk factors and multinomial logistic regression were analyzed. RESULTS: (1) Clinical characteristics: The incidence of patients with dysmenorrhea, dyspareunia, straining feeling in anus, chronic pelvic pain and the level of CA(125) (> 35 kU/L) was remarkably higher in moderate-to-severe adhesion groups than in none-to-mild adhesions groups (P = 0.000, 0.000, 0.001, 0.006 and 0.000, respectively). Infertility rate were significantly higher in severe adhesions group (15.7%, 31/198) than none adhesions group (3.2%, 1/31), mild adhesions group (11.4%, 14/123) and moderate adhesions group (9.7%, 30/310, OR = 1.728, P < 0.05). (2) Operating time and blood loss: Operating time of each groups was as followed: (37 +/- 15) min in none adhesions group, (42 +/- 19) min in mild adhesions group, (50 +/- 20) min in moderate adhesions group and (63 +/- 22) min in severe adhesion group. Blood loss was (23 +/- 12) ml in none adhesion group, (31 +/- 27) ml in mild adhesion group, (40 +/- 32) ml in moderate adhesion group and (70 +/- 67) ml in severe adhesions group. Thicker adhesions result in longer operation time and more blood loss. (3) Combined with other disease: The ratio of patients who combined with adenomyosis or deeply infiltrating endometriosis in moderate-to-severer adhesion groups was higher than patients in none-to-mild adhesions groups (OR = 3.466, P = 0.000). (4) Postoperative recurrence: It was categorized into recurrence of pain and cyst. Moderate-to-severe adhesions was related to higher recurrence rate of pain (OR = 1.685, P = 0.046), but was irrelevant to recurrence of cyst. CONCLUSION: The more extent of endometrioma adhesions was related to severer pelvic pain symptoms, longer operating time and more blood loss. Postoperative pain recurrence rate was observed in moderate-to-severe adhesion group. Extent of adhesions was irrelevant to cyst recurrence.

Zhonghua Fu Chan Ke Za Zhi. 2009 May;44(5):321-3.

Current status and future direction of research on pelvic pain associated with endometriosis

[Article in Chinese]

Leng JH.

Acta Obstet Gynecol Scand. 2009;88(8):914-9.

Life after a diagnosis with endometriosis – a 15 years follow-up study.

Fagervold B, Jenssen M, Hummelshoj L, Moen MH.

Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

OBJECTIVE: Previous studies have elucidated the negative impact of endometriosis on life, but the patient selection may have contributed to a skewed picture. The aim of this study was to investigate longitudinally the consequences of the disease in women diagnosed with endometriosis 15 years ago. DESIGN: Retrospective descriptive. SETTING: Trondheim 2007. SAMPLE: One hundred thirty women diagnosed with endometriosis at St. Olav’s Hospital in Trondheim between 1991 and 1993. METHODS: Questionnaires. Response rate of 60%. MAIN OUTCOME MEASURES: Consequences of living with endometriosis. RESULTS: Of the women, 19.2% never experienced pelvic pain and 21.8% did not have any further visits to the gynecological department after being diagnosed. Almost 70% had received pharmaceutical treatment and positive effect on pain was reported by 41% for NSAIDs and oral contraceptives, and by 62% for progestins and GnRH-analogues. Satisfactory effect on pain after surgical interventions at the time of diagnosis was reported by 60.9%, and by 89.9% after later surgeries. Of the infertile patients, 75.6% succeeded in delivering one or more biological children. Half of the women reported that endometriosis had some negative impact on their lives. After menopause, 96.9% were free from pain. CONCLUSION: This study confirms that endometriosis is a condition that often has considerable impact on a woman’s life. However, the study also found that endometriosis does not always cause pain, that treatment in many cases is effective, that infertility may be overcome, and that almost all postmenopausal women were free from endometriosis-associated pain.

Abdom Imaging. 2009 Jun 30. [Epub ahead of print]

Evaluation of colonic involvement in endometriosis: double-contrast barium enema vs. magnetic resonance imaging.

Faccioli N, Foti G, Manfredi R, Mainardi P, Spoto E, Ruffo G, Minelli L, Mucelli RP.

Department of Radiology, G.B. Rossi Hospital, University of Verona, Piazzale Scuro 10, 37134, Verona, Italy, nfaccioli@sirm.org.

BACKGROUND: The purpose of the study was to compare the accuracy of double-contrast barium enema (DCBE) and magnetic resonance imaging (MRI) in the diagnosis of intestinal endometriosis using the histological examination on resected specimen as comparative standard. METHODS: Eighty-three consecutive patients with suspected intestinal endometriosis, resected between 2005 and 2007, were prospectively evaluated. All of the women underwent preoperative DCBE and MRI on the same day. We evaluated number, site (rectum, sigmoid, cecum), and size of the lesions. The imaging findings were correlated with those resulting at pathology. RESULTS: Among the 65 women who underwent surgery, 50/65 (76.9%) were found to have bowel endometriosis, with 9/50 (18%) patients presenting two lesions; DCBE allowed to detect 50/59 (84.7%) lesions. MRI allowed to detect 42/59 (71.1%) lesions. DCBE showed sensibility, specificity, PPV, NPV, and accuracy of respectively 84.7, 93.7, 98.0, 62.5, and 86.6%, MRI of 71.1, 83.3, 93.3, 46.8, and 74.6%. CONCLUSION: DCBE is more accurate than unenhanced MRI in the diagnosis of bowel endometriosis, and should be preferred in the preoperative management of this disease, since it usually enables a proper surgical planning.

Arch Gynecol Obstet. 2009 Jun 30. [Epub ahead of print]

Severe endometriosis: laparoscopic rectum resection.

Juhasz-Böss I, Lattrich C, Fürst A, Malik E, Ortmann O.

Department of Obstetrics and Gynecology, University Medical Center Regensburg, Landshuterstr. 63, 93053, Regensburg, Germany, ingolf.juhasz-boess@klinik.uni-regensburg.de.

AIM: Endometriosis is a frequent benign disease of women in reproductive age. An infiltration of the spatium rectovaginal is rare, but if it occurs, in up to 73% the rectum is involved. If there is the indication for surgery, a partial resection of the rectum might be necessary. This can be performed by a laparoscopic approach. It is the aim of this work to describe a patient population treated for endometriosis in the spatium rectovaginal by laparoscopic surgery. PATIENT POPULATION AND METHODS: A retrospective analysis of data from patients with endometriosis in rectum or sigma, which underwent a laparoscopic partial bowel resection in the years 2005-2006 at the Department of Obstetrics and Gynecology, University of Regensburg, was carried out. RESULTS: Between 2005 and 2006, we performed a laparoscopic partial bowel resection in six patients with endometriosis. The mean age at diagnosis was 36.1 years (range 28-50 years) and 36.5 years (range 30-50 years) at surgery. All patients were nulligravida and 50% of the patients were infertile (since 1-6 years). The interval between the onset of symptoms and surgery ranged from a few weeks up to 2.5 years. Two-thirds of the patients had endocrine treatment before surgery. Three patients had a rectum resection, one a sigma resection and two had a combined rectum- and sigma resection. The mean duration of surgery was 201 min and mean hospital stay was 8 days. We saw one post-surgery bleeding at the enteroanastomosis. In that case two erythrocyte concentrates were necessary and the bleeding was stopped by rectoscopic intervention. All follow-up coloscopies were without pathological findings. One patient had a normal delivery after IVF/ICSI treatment. CONCLUSIONS: If severe endometriosis needs a rectum resection then it can be done laparoscopically. This surgery should be performed in a specialized center. The duration of surgery, hospital stay and time of convalescence are short.

Gynecol Endocrinol. 2009 Jun 26:1-4. [Epub ahead of print]

Appendectomy in retrograde order for complete removal of endometriosis.

Lim MC, Song YJ, Lee DO, Jung DC, Yoo CW, Park SY.

Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea.

Endometriosis frequently involves the intestines. Appendectomy would be often required as part of complete removal of endometriosis. We present a patient with endometriosis who required very difficult appendectomy. For complete removal of endometriosis, hysterectomy, bilateral salpingooophorectomy, low anterior resection and accompanying pelvic peritonectomy were performed through a mid-line incision. Unexpectedly, the appendiceal tip was attached to peri-hepatic tissue with the appendix adhered to the surrounding peritoneum and bowel. Completion of the appendectomy was possible in retrograde order after extension of the surgical incision above the umbilicus. Our findings suggest that preoperative image evaluation for location or position of the appendix might be helpful in patients with suspected endometriosis to offer correct counselling, obtaining adequate consent, determining the optimal surgical approach and scheduling opportune intraoperative consultation by a colorectal surgeon.

Agri. 2009 Apr;21(2):75-9.

Reflex sympathetic dystrophy secondary to piriformis syndrome: a case report

[Article in Turkish]

Akçali D, Taş A, Cizmeci P, Oktar S, Zinnuroğlu M, Arslan E, Köseoğlu H, Babacan A.

Department of Anesthesiology and Reanimation, Algology Department, Gazi University Faculty of Medicine, Ankara, Turkey. didemakcali@yahoo.com

Piriformis syndrome is a rare cause of hip and foot pain which may be due to sciatic nerve irritation because of anatomic abnormalities of sciatic nerve and piriformis muscle or herniated disc, facet syndrome, trochanteric bursit, sacroiliac joint dysfunction, endometriosis and other conditions where sciatic nerve is irritated. There has been no reflex sympathetic dystrophy (RSD) case presented due to piriformis syndrome before. A sixty-two-year-old female patient had right foot and hip pain (VNS: 8), redness and swelling in the foot since 15 days. Her history revealed long walks and travelling 3 weeks ago and sitting on the foot for a long time for a couple of days. Physical examination revealed painful hip movement, positive straight leg rise. Erythema and hyperalgesia was present in dorsum of the right foot. Right foot dorsiflexion was weak and hyperesthesia was found in right L4-5 dermatome. Medical treatment and ultrasound treatment to piriformis muscle was not effective. The patient was injected 40 mg triamcinolon and local anesthetic in right piriformis muscle under floroscopy by diagnosis of piriformis syndrome, neuropathic pain and RSD. Pain and hyperalgesia resolved and motor weakness was better. During follow-up right foot redness resolved and pain decreased (VNS: 1). In this case report, there was vascular, muscle and skeletal signs supporting RSD, which shows us the therapoetic effect of diagnostic piriformis injection. The patient history, physical examination and diagnostic tests were evaluated by a multidisciplinary team which contributed to the treatment.

Publication Types:

Fertil Steril. 2009 Jul;92(1):e3.

Comment on:

Reply of the authors to the letter by Broek et al. on June 9, 2008.

Pellicano M, Bramante S, Guida M, Bifulco G, Di Spiezio Sardo A, Cirillo D, Nappi C.

Publication Types:

Gynecol Obstet Invest. 2009;68(2):116-21. Epub 2009 Jun 24.

Interval of injections of intramuscular depot medroxyprogesterone acetate in the long-term treatment of endometriosis-associated pain: a randomized comparative trial.

Cheewadhanaraks S, Peeyananjarassri K, Choksuchat C, Dhanaworavibul K, Choobun T, Bunyapipat S.

Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110 Thailand. csophon@medicine.psu.ac.th

AIM: To determine the optimal interval of injections of intramuscular depot medroxyprogesterone acetate 150 mg in the long-term treatment of endometriosis-associated pain. METHOD: 112 patients with symptomatic endometriosis were randomized to receive either injections every month for 6 months, then every 3 months for a total of 15 months or injections every 3 months for 15 months. The primary outcome measure was patients’ satisfaction. RESULT: At months 3, 6, 9, 12 and 15 of the treatment phase, there was no statistically significant difference of percentages of patients with satisfaction between the two regimens (85.7 vs. 76.8%, 76.8 vs. 73.2%, 66.1 vs. 58.9%, 60.7 vs. 55.4%, 60.7 vs. 55.4%, respectively). CONCLUSION: The optimal interval of injections of depot medroxyprogesterone acetate 150 mg is every 3 months. Copyright 2009 S. Karger AG, Basel.

Publication Types:

Eur J Cancer Prev. 2009 Aug;18(4):316-21.

Hormone-related factors and gynecological conditions in relation to endometrial cancer risk.

Zucchetto A, Serraino D, Polesel J, Negri E, De Paoli A, Dal Maso L, Montella M, La Vecchia C, Franceschi S, Talamini R.

SOC Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.

The objective of this study is to investigate the effect of menstrual and reproductive variables, breastfeeding, exogenous hormones, and gynecological conditions on endometrial cancer risk. We conducted a case-control study in Italy, including 454 women with endometrial cancer and 908 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Endometrial cancer risk was inversely associated with age at menarche (OR = 0.7, 95% CI = 0.5-1.0, for > or =14 vs. <12 years), and directly associated with age at menopause (OR = 1.8, 95% CI = 1.1-2.7, for > or =55 vs. <50 years) and years of menstruation (OR = 2.4, 95% CI = 1.7-3.4, for highest vs. lowest tertile). Multiparity strongly reduced the risk among women under 60 years of age (OR = 0.3, 95% CI = 0.2-0.6, for > or =3 deliveries vs. <2). Oral contraceptive use conferred a 40% reduced risk (95% CI = 0.4-1.0), irrespective of time since cessation. Although based on small numbers, women with a history of treated infertility (OR = 2.7, 95% CI = 1.1-6.4) or endometriosis (OR = 4.0, 95% CI = 1.0-15.5) were at increased risks. No significant associations with endometrial cancer risk emerged for age at first/last birth, breastfeeding, menopausal status, hormone replacement therapy, and history of uterine fibromyomas or polycystic ovary. In conclusion, this study confirms the importance of multiparity, years of menstruation, and oral contraceptive use in endometrial cancer etiology, thus contributing to identify women at elevated risk of such neoplasm.

Publication Types:

Genet Mol Res. 2009 May 5;8(2):494-9.

Analysis of p53 codon 72 gene polymorphism in Brazilian patients with endometriosis.

Ribeiro Júnior CL, Arruda JT, Silva CT, Moura KK.

Centro de Medicina Fetal e Reprodução Humana – FERTILE, Goiânia, GO, Brasil.

We examined the frequency of p53 codon 72 polymorphism in 38 patients with endometriosis whose diagnosis was confirmed using videolaparoscopy. Half of the women were infertile. There were no significant differences in the genotype (P = 0.0927) or allele frequencies (P = 0.1430) for p53 Arg72Pro polymorphism between the two groups. We found a significant association between the heterozygous and homozygous proline genotypes and intense pain in the patients. Sixty-four percent of the patients were homozygous or heterozygous for proline in patients with degree III or IV endometriosis, but there was no significant difference compared to homozygous arginine genotype (P = 0.6115). We found that the proline allele is associated with substantial complaints (infertility associated with pain), when compared to the homozygous arginine genotype; we also found that the proline allele was more frequent in endometriosis patients.

Publication Types:

J Vis Exp. 2009 Jun 23;(28). pii: 1232. doi: 10.3791/1232.

Demonstration of cutaneous allodynia in association with chronic pelvic pain.

Jarrell J.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Calgary.

Pelvic pain is a common condition that is associated with dysmenorrhea and endometriosis. In some women the severe episodes of cyclic pain change and the resultant pain becomes continuous and this condition becomes known as Chronic Pelvic Pain. This state can be present even after the appropriate medical or surgical therapy has been instituted. It can be associated with pain and tenderness in the muscles of the abdomen wall and intra-pelvic muscles leading to severe dyspareunia. Additional symptoms of irritable bowel and interstitial cystitis are common. A common sign of the development of this state is the emergence of cutaneous allodynia which emerges from the so-called viscero-somatic reflex. A simple bedside test for the presence of cutaneous allodynia is presented that does not require excessive time or special equipment. This test builds on previous work associated with changes in sensation related to gall bladder function and the viscera-somatic reflex(1;2). The test is undertaken with the subject s permission after an explanation of how the test will be performed. Allodynia refers to a condition in which a stimulus that is not normally painful is interpreted by the subject as painful. In this instance the light touch associated with a cotton-tipped applicator would not be expected to be painful. A positive test is however noted by the woman as suddenly painful or suddenly sharp. The patterns of this sensation are usually in a discrete pattern of a dermatome of the nerves that innervate the pelvis. The underlying pathology is now interpreted as evidence of neuroplasticity as a consequence of severe and repeating pain with changes in the functions of the dorsal horns of the spinal cord that results in altered function of visceral tissues and resultant somatic symptoms(3). The importance of recognizing the condition lies in an awareness that this process may present coincidentally with the initiating condition or after it has been treated. It also permits the clinician to evaluate the situation from the perspective that alternative explanations for the pain may be present that may not require additional surgery.

Publication Types:

Cancer Res. 2009 Jul 1;69(13):5415-23. Epub 2009 Jun 23.

Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.

Lin BC, Suzawa M, Blind RD, Tobias SC, Bulun SE, Scanlan TS, Ingraham HA.

Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, USA.

Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.

Publication Types:

Hum Reprod. 2009 Oct;24(10):2600-6. Epub 2009 Jun 23.

High serum follistatin levels in women with ovarian endometriosis.

Florio P, Reis FM, Torres PB, Calonaci F, Abrao MS, Nascimento LL, Franchini M, Cianferoni L, Petraglia F.

Division of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico Le Scotte, Siena, Italy.

BACKGROUND: Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker. METHODS: Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125. RESULTS: Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P < 0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P < 0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P < 0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P < 0.001) and serum (P < 0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P < 0.0001). CONCLUSIONS: Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.

Publication Types:

Reprod Biomed Online. 2009 May;18(5):651-7.

Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report.

Altmäe S, Haller K, Peters M, Saare M, Hovatta O, Stavreus-Evers A, Velthut A, Karro H, Metspalu A, Salumets A.

Department of Biotechnology, Institute of Molecular and Cell Biology, Estonian Genome Foundation, University of Tartu, Estonia.

Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.

Publication Types:

Reprod Sci. 2009 Jun 22. [Epub ahead of print]

In Vitro Models to Study the Pathogenesis of Endometriosis.

Griffith JS, Rodgers AK, Schenken RS.

Several in vitro models that attempt to replicate the intraperitoneal environment have been developed to study the pathogenesis of endometriosis. The chicken chorioallantotic membrane has been used, but it has not been well characterized and may introduce some species specific variables. In vitro models using human tissues include amniotic membrane, human peritoneal explants, and cell culture monolayers. These models have been used to qualitatively, quantitatively, and temporally assess attachment of endometrial cells to peritoneal mesothelial and subsequent transmesothelial invasion. These models have also been used to assess the role of cytokines in the development of the early endometriotic lesion. Two- and three dimensional invasion chamber models have been utilized to assess endometrial cell interactions with peritoneal mesothelial cells and the extracellular matrix. Invasion models are also useful to evaluate novel therapeutic approaches. This review will focus on the above models to assist reproductive scientists interested in the pathogenesis of endometriosis.

Int J Gynaecol Obstet. 2009 Oct;107(1):68-9. Epub 2009 Jul 9.

Papillary serous carcinoma in situ in ovarian endometriosis in an MSH2 mutation carrier.

Vaknin Z, Gotlieb WH, Arseneau J, Ferenczy A.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.

Publication Types:

Folia Biol (Praha). 2009;55(3):92-7.

Leukaemia inhibitory factor (LIF) gene mutations in women diagnosed with unexplained infertility and endometriosis have a negative impact on the IVF outcome. A pilot study.

Novotný Z, Krízan J, Síma R, Síma P, Uher P, Zech N, Hütelová R, Baborová P, Ulcová-Gallová Z, Subrt I, Ulmanová E, Houdek Z, Rokyta Z, Babuska V, Králícková M.

Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital, Department of Obstetrics and Gynecology, Pilsen, Czech Republic.

The frequency of functionally relevant mutations of the leukaemia inhibitory factor (LIF) gene in infertile women is significantly enhanced in comparison with fertile controls. The objective of this retrospective cohort study was to evaluate the impact of LIF gene mutations on the outcome of the treatment in women with various causes of infertility. Fifteen infertile women with the G to A transition at position 3400 leading to the valine to methionine exchange at codon 64 were analysed. Group A was made up of women with diagnoses that are frequently accompanied by changes in humoral as well as cell-mediated immunity – idiopathic infertility and endometriosis (N = 7). Group B consisted of patients with polycystic ovary syndrome (PCOS), andrological factor, tubal factor and hyperprolactinaemia (N = 8). The control group comprised 136 infertile women with no LIF gene mutation diagnosed with idiopathic infertility and endometriosis (N = 37) (group C) and patients with PCOS, tubal and andrological factor (N = 99) (group D). Seven of the mutation-positive patients were successfully treated by in vitro fertilization (IVF), but nobody in this group was diagnosed with idiopathic infertility and only one with endometriosis, which means that there is a statistically significant difference in the pregnancy rates between groups A and B (P = 0.01, Fisher’s 2 by 2 exact test) but no statistically significant difference when comparing patients with the LIF gene mutation (group A+B) to no LIF gene mutation (group C+D). The results suggest that in mutation-positive women the idiopathic infertility and endometriosis have a negative impact on the outcome of IVF treatment.

Publication Types:

Research Support, Non-U.S. Gov’t

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