Fertil Steril. 2010 Feb;93(3):1007.e1-3. Epub 2009 Nov 25.

A multidisciplinary, minimally invasive approach for complicated deep infiltrating endometriosis.

Seracchioli R, Manuzzi L, Mabrouk M, Solfrini S, Frascà C, Manferrari F, Pierangeli F, Paradisi R, Venturoli S.

Minimally Invasive Gynecological Surgery Unit, Reproductive Medicine Unit, S. Orsola Hospital, University of Bologna, Italy. seracchioli@aosp.bo.it

OBJECTIVE: To present a case of complicated deep infiltrating endometriosis managed by a multidisciplinary minimally invasive approach. DESIGN: Case report. SETTING: Tertiary care university hospital. PATIENT: A 32-year-old woman with deep infiltrating endometriosis involving the rectovaginal septum, the rectum, and the left ureter, complicated by silent left renal function loss. INTERVENTION(S): Laparoscopic left nephrectomy, ureterectomy, excision of a left ovarian endometrioma, removal of a large rectovaginal nodule, and segmental bowel resection with minilaparotomic end-to-end anastomosis. MAIN OUTCOME MEASURE(S): Multidisciplinary diagnosis and minimally invasive surgical approach to deep infiltrating endometriosis involving the rectum and the urinary tract. RESULT(S): Collaboration between gynecologists, urologists, and colorectal surgeons enabled a successful management of the case in one surgical intervention providing minor risk of complications, shorter hospital stay, and faster functional recovery. CONCLUSION(S): Deep infiltrating endometriosis is a global pathology that may involve different structures. A multidisciplinary, minimally invasive approach should be recommended to achieve appropriate disease management. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Expert Opin Ther Pat. 2009 Dec;19(12):1771-85.

Luteinizing hormone-releasing hormone antagonists.

Mezo G, Manea M.

Eötvös Loránd University, Hungarian Academy of Sciences, Research Group of Peptide Chemistry, Budapest, Pázmány P. stny. 1/A, Hungary. gmezo@elte.hu

BACKGROUND: Luteinizing hormone-releasing hormone (LH-RH) plays a central role in the vertebrate reproduction by regulating gonadal activity. Based on its binding to pituitary LH-RH receptors, as well as to LH-RH receptors expressed on cancer cells, LH-RH agonists and antagonists have been developed for different therapeutic applications. OBJECTIVE/METHOD: Here we give an overview of the most relevant LH-RH antagonists and their therapeutic applications. Recently patented compounds as well as drug formulations and dosage are presented. CONCLUSION: LH-RH antagonists have found clinical applications in in vitro fertilization, benign prostatic hyperplasia, endometriosis and in the treatment of hormone-dependent tumors. Work in progress is focused on further development of both peptidic and orally active non-peptidic LH-RH antagonists.

Diagn Cytopathol. 2009 Nov 23. [Epub ahead of print]

Papanicolaou tests associated with cervical mucosal endometriosis: An analysis of cellular features and comparison to endocervical adenocarcinoma in situ.

Biscotti CV, Ray N.

Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.

Endometrium directly sampled from endocervical mucosal endometriosis can mimic endocervical adenocarcinoma in situ (AIS) in Papanicolaou (Pap) tests. We analyzed a series of Pap tests to investigate the cellular features of mucosal endometriosis and to assess the utility of stroma and apoptotic bodies in the differential diagnosis with AIS. Pap test samples from patients known to have endocervical mucosal endometriosis were compared with samples containing AIS. Pap tests from patients with mucosal endometriosis had lesional cells in 13 (62%) cases which includes glandular and stromal cells (10 cases), stroma only (two cases), and glandular cells only (one case). Three (23%) cases had gland-stromal aggregates. Three (23%) cases had mitotic figures and two (15%) had apoptotic bodies. By comparison, only one (8%) AIS case had endometrial-type stroma. Seven (58%) AIS cases had apoptotic bodies and three (25%) had mitotic figures. We conclude that Pap tests from patients with mucosal endometriosis usually (62%) have lesional cells. These lesional cells almost always include stroma, which is useful in the differential diagnosis with AIS. We identified stroma significantly more often in endometriosis cases (92%) than in AIS cases (8%). Pathologists should look for endometrial stroma when considering an interpretation of directly sampled endometrium. In the absence of stroma, AIS should be considered. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc.

Int Urogynecol J Pelvic Floor Dysfunct. 2010 Mar;21(3):321-4.

Intravesical lignocaine in the diagnosis of bladder pain syndrome.

Taneja R.

Pushpawati Singhania Research Institute, Press Enclave Road, Sheikh Sarai, Phase II, New Delhi 17, India. rajeshtanejadr@rediffmail.com

INTRODUCTION AND HYPOTHESIS: To differentiate between the pain originating from urinary bladder and that due to other pelvic organs, using intravesical instillations of 2% lignocaine solution. METHODS: Twenty-two women with pelvic pain received intravesical instillation of 20 ml of 2% lignocaine solution. The intensity of pain was recorded by using visual analogue scale (VAS) just before, at 2, 10 and 20 min after intravesical instillation. Women who experienced a drop in the VAS score by 50% were termed as responders. All these women underwent cystoscopy under anaesthesia. RESULTS: Fifteen out of 22 (68.18%) women experienced a substantial reduction in the pain. Thirteen out of these 15 women had features suggestive of BPS/IC on cystoscopy. Out of the seven non-responders, two women were found to have endometriosis, four were diagnosed as pelvic inflammatory disease and one had diverticulitis. CONCLUSIONS: Intravesical lignocaine appears to be useful in excluding patients with pelvic pain originating from organs other than the urinary bladder.

Vet Rec. 2009 Nov 21;165(21):623-6.

Effects of the administration of oxytocin or carbetocin to dairy cows at parturition on their subsequent fertility.

Barrett AJ, Murray RD, Christley RM, Dobson H, Smith RF.

Kingsway Veterinary Group, 73 Otley Road, Skipton, North Yorkshire BD23 1HJ.

A total of 501 dairy cows were allocated sequentially to be treated immediately after parturition with either 25 iu oxytocin or 35 mg carbetocin, or to be left untreated. Any abnormal parturition, including assisted calving, the birth of twins or dead calves, retained fetal membranes or hypocalcaemia, was recorded, and the cows were examined between 28 and 42 days after calving for endometritis. Pregnancy was diagnosed from 30 days after insemination. The incidence of endometritis was similar (14 per cent, 16 per cent and 19 per cent) and the median intervals from calving to pregnancy were similar (118, 121 and 119 days) for the cows treated with oxytocin, carbetocin or receiving no treatment, respectively. The incidence of endometritis and the median intervals from calving to pregnancy were also similar between the groups for the cows that had an abnormal parturition.

Reprod Sci. 2010 Mar;17(3):278-87. Epub 2009 Nov 20.

Regulation of monocyte chemotactic protein-1 expression in human endometrial endothelial cells by sex steroids: a potential mechanism for leukocyte recruitment in endometriosis.

Luk J, Seval Y, Ulukus M, Ulukus EC, Arici A, Kayisli UA.

Section of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(- 8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Mol Cell Endocrinol. 2010 Apr 12;317(1-2):31-43. Epub 2009 Nov 22.

17betaE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFkappaB-dependent pathway.

Zhang H, Zhao X, Liu S, Li J, Wen Z, Li M.

Department of Obstetrics & Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, PR China.

The objective of this study was to explore the mechanism of phosphatase and tensin homolog (PTEN) loss in endometriosis. We found that aberrant PTEN expression and mitogen-activated protein kinases (MAPK)/ERK, phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFkappaB) signaling overactivities coexisted in endometriosis. In vitro, 17beta-estradiol rapidly activated the 3 pathways in endometriotic cells and specific inhibitions on the 3 pathways respectively blocked 17beta-estradiol-induced cell proliferation. 17beta-estradiol suppressed PTEN transcription and expression in endometriotic cells which was abolished by specific NFkappaB inhibition. CONCLUSION(S): Total/nuclear PTEN-loss and MAPK/ERK, PI3K/AKt, and NFkappaB signal overactivities coexist in endometriosis. In vitro, 17beta-estradiol can promotes cell proliferation in endometriosis by activating PI3K/AKt pathway via an NFkappaB/PTEN-dependent pathway. For the first time we propose the possibility of the presence of a positive feedback-loop: 17beta-estradiol–>high NFkappaB–>low PTEN–>high PI3K–>high NFkappaB, in endometriosis, which may finally promote the proliferation of ectopic endometrial epithelial cells and in turn contributes to the progression of the disease.

Minim Invasive Ther Allied Technol. 2009;18(6):317-21.

Analysis of factors affecting vaginal hysterectomy.

Hong DG, Seong WJ, Lee YS, Cho YL.

Department of Obstetrics and Gynecology, Kyungpook National University Graduate School of Medicine, Daegu, Korea.

The study analyzes factors that affect vaginal hysterectomy to establish the indications of a vaginal approach to benign uterine disease. In a retrospective study, 174 patients underwent vaginal hysterectomy for uterine leiomyomas or adenomyosis by one gynecologist between December 2005 and December 2006. All data were compared and analyzed by X(2)- test, t-test, and multiple logistic regression. Based on a uterine weight > or = 500 g, body weight, a history of surgery, concomitant surgery (adenexectomy), penetration of the posterior cul de sac during surgery, uterine descent, and average uterine weight we determined the feasibility of vaginal hysterectomy. Based on an operative time > or = 33 min, body weight, concomitant surgery (adenexectomy), penetration of the posterior cul de sac, vertical length of the vaginal opening, uterine descent, and the uterine weight had significant effects on the success of vaginal hysterectomy. The range of indications for vaginal hysterectomy may vary greatly depending on the surgeon’s experience. If experiences are accumulated gradually, together with the advantages of laparoscopically assisted hysterectomy, most abdominal hysterectomies and laparoscopic hysterectomies can be replaced by vaginal hysterectomy.

Bioorg Med Chem Lett. 2010 Jan 1;20(1):371-4. Epub 2009 Oct 25.

Improving the developability profile of pyrrolidine progesterone receptor partial agonists.

Kallander LS, Washburn DG, Hoang TH, Frazee JS, Stoy P, Johnson L, Lu Q, Hammond M, Barton LS, Patterson JR, Azzarano LM, Nagilla R, Madauss KP, Williams SP, Stewart EL, Duraiswami C, Grygielko ET, Xu X, Laping NJ, Bray JD, Thompson SK.

Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. lara.s.kallander@gsk.com

The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein. Copyright 2009 Elsevier Ltd. All rights reserved.

Eur J Obstet Gynecol Reprod Biol. 2010 Mar;149(1):117-8. Epub 2009 Nov 18.

Massive ascites, pleural effusion, and diaphragmatic implants in a patient with endometriosis.

Ignacio MM, Joseph N, Hélder F, Mamourou K, Arnaud W.

IRCAD/EITS and Strasbourg University Hospitals, Faculty of Medicine, Strasbourg, France.

Gynecol Oncol. 2010 Mar;116(3):374-7.

When ‘never-events’ occur despite adherence to clinical guidelines: the case of venous thromboembolism in clear cell cancer of the ovary compared with other epithelial histologic subtypes.

Duska LR, Garrett L, Henretta M, Ferriss JS, Lee L, Horowitz N.

Division of Gynecologic Oncology, University of Virginia Health Systems, Charlottesville, VA 22903, USA. lduska@virginia.edu

OBJECTIVE: To determine the incidence of clinically significant venous thromboembolism (VTE) in women diagnosed with clear cell carcinoma of the ovary (CCC-O) interpreted in the context of Centers for Medicare and Medicaid Services (CMS) ‘never-events.’ METHODS: Using the institutional pathology Tumor Registry at the Massachusetts General Hospital (MGH), all women diagnosed with a CCC-O from 1994 to 2004 were identified. Controls with epithelial ovarian cancer of other histologies were matched for stage, age and year of diagnosis. Medical records were abstracted and pathology reviewed. All patients had surgical staging and/or cytoreductive surgery by a Gynecologic Oncologist at the MGH. All patients received appropriate peri- and post-operative prophylaxis with subcutaneous heparin and/or sequential compression devices. VTE was diagnosed with standard imaging techniques when clinical suspicion arose. RESULTS: Fifty-eight (58) women were diagnosed with CCC-O during the study period, 43 of whom had complete data available for analysis. Patients with Stage I or II disease comprised 70% of the patients. The mean age of the cohort was 55 and the mean weight 71 kg. Eighty-six (86) age, stage, and year of diagnosis matched controls were selected. The majority of controls had serous tumors (47%) with the remainder being endometrioid (33%), mucinous (14%), transitional cell (2%), sarcoma (2%) and mixed (2%). CCC-O was often seen in association with endometriosis 70% compared with 22% of controls (p<0.0001). Overall, 18 of 43 CCC-O patients (42%) had VTE while only 19 of 86 control patients (22%) had VTE (p=0.024, OR=2.5 CI 1.1504-5.60). The rate of VTE was not influenced by weight or smoking. In the CCC-O patients, seventeen percent (17%) of VTE was diagnosed at presentation while 50% was diagnosed postoperatively and 33% at the time of disease recurrence or progression. Overall, including cases and controls, late stage disease was more likely associated with VTE (18 of 39, 46%) vs. early stage disease (19 of 90, 21%), p=0.004. CONCLUSIONS: Women with CCC-O have a 2.5-times greater risk of disease related VTE than women with other histologies of epithelial ovarian cancer despite adherence to prophylactic guidelines. Given the high rate of VTE postoperatively as well as with disease recurrence, one should consider indefinite therapeutic anticoagulation in women with CCC-O. The case of CCC-O is one example of the impracticality of payment denial for ‘never-events,’ as VTE arises despite best efforts at prevention.

Hum Reprod. 2009 Dec;24(12):2972-3.

All that glistens is not gold.

Evers JL, Van Steirteghem AC.

Comment on:

Ann Diagn Pathol. 2009 Dec;13(6):373-7.

Cyclooxygenase-2 expression, Ki-67 labeling index, and perifocal neovascularization in endometriotic lesions.

Horn LC, Hentschel B, Meinel A, Alexander H, Leo C.

Department of Breast, Gynecologic and Perinatal Pathology, Institute of Pathology, University of Leipzig, D-04103 Leipzig, Germany. hornl@medizin.uni-leipzig.de

There is a suggested pathogenetic role of cyclooxygenase-2 (COX-2) in endometriosis via angiogenesis and proproliferative mechanisms. The aim of the study was to investigate the immunohistochemical COX-2 expression in different anatomical sites of endometriosis and its correlation to proliferative activity and periendometriotic vascularization. Sixty endometrioses from different sites (ovarian, uterine, and peritoneal) were evaluated immunohistochemically for COX-2 expression. Cyclooxygenase-2 staining of 75% or more of the cells was defined as COX-2 overexpression and used as cutoff. Proliferative activity was determined by performing Ki-67-labeling index. Periendometriotic vascularization was evaluated by determining microvessel density surrounding the endometriotic focus using CD-34-immunostaining. Cyclooxygenase-2 overexpression was significant more frequent in ovarian endometriosis, when compared with uterine and peritoneal localization (70.8% versus 41.7%; P = .027). There was no significant correlation between COX-2 overexpression and perifocal neovascularization (P = .49). Endometriotic lesions with COX-2 overexpression represented reduced proliferative activity (P = .055). Cyclooxygenase-2 is expressed in the majority of endometriosis, but differences exist within the frequency of overexpression at different anatomical sites of the endometriosis. Cyclooxygenase-2 inhibitors are of clinical interest as treatment options.

Hum Reprod. 2010 Feb;25(2):406-11. Epub 2009 Nov 12.

Altered glycosylation in peri-implantation phase endometrium in women with stages III and IV endometriosis.

Miller DL, Jones CJ, Aplin JD, Nardo LG.

Academic Health Sciences Centre, Maternal and Fetal Health Research Group, University of Manchester, St Mary’s Hospital, 5th Floor (Research), Oxford Road, Manchester M13 9WL, UK.

BACKGROUND: Endometriosis is a common cause of infertility and pelvic pain. Lectin histochemistry has shown that glycan expression is a sensitive marker of differentiation in the normal endometrium. Endometrial biopsies were taken during the implantation window from women with subfertility and advanced (stage III and IV) endometriosis to evaluate specific glycans bound by lectins from Dolichos biflorus agglutinin (DBA) and Vicia villosa agglutinin (VVA), which detect related but distinct glycan sequences regulated by progesterone action. METHODS: Endometrial tissue from 12 women with subfertility and advanced endometriosis and 11 healthy controls were taken on days 19-24 of the menstrual cycle and processed into either epoxy resin or paraffin wax. Lectin histochemistry was analysed using light microscopy to quantify the amount of glandular reaction product. RESULTS: There was a significant (P = 0.011) reduction in DBA binding to endometrium from patients with endometriosis compared with controls, which was not seen with VVA (P = 0.135). Three stage IV biopsies and one stage III biopsy completely failed to bind DBA and, of these, three showed moderate glandular binding of VVA. DBA and VVA binding differed significantly (P= 0.0039) in the endometriosis specimens whereas in controls no significant difference was detected (P = 0.812). CONCLUSION: Secretory phase glycosylation in women with advanced endometriosis differs from that in healthy women with a reduction in fucosylated N-acetylgalactosamine sequences bound by DBA. Shorter VVA-binding glycans are not significantly affected. In addition to indicating abnormalities of epithelial differentiation, these findings may be directly relevant to implantation failure, as blastocyst attachment requires a critical interaction with the epithelial glycocalyx.

Hum Reprod. 2010 Feb;25(2):387-91. Epub 2009 Nov 12.

Neuroendocrine cells in eutopic endometrium of women with endometriosis.

Wang G, Tokushige N, Russell P, Dubinovsky S, Markham R, Fraser IS.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China. wangguoy@sdu.edu.cn

BACKGROUND: Endometriosis is a common gynaecological disease, but the pathogenesis of endometriosis and pathophysiological basis for endometriosis-associated painful symptoms are still uncertain. Little is known about neuroendocrine (NE) cells in the uterus. METHODS: For this study, 38 premenopausal women with histologically diagnosed ovarian endometrioma or peritoneal endometriosis and 24 women without endometriosis were selected. Biopsy samples from eutopic endometrium were used for immunohistochemical staining to detect synaptophysin (SYN) and neuron-specific enolase (NSE) expression in women with and without endometriosis. RESULTS: There were substantially more NE cells of eutopic endometrium stained with SYN and NSE in women with endometriosis than in those without endometriosis (3.8 +/- 1.8 versus 0.5 +/- 0.7/mm2, P < 0.001, and 2.8 +/- 2.1 versus 0.4 +/- 0.6/mm2, respectively, P < 0.001). These cells were scattered in the epithelium of endometrial glands. At all stages of the menstrual cycle, the densities of NE cells stained with SYN and NSE were greater in women with endometriosis than in those without endometriosis (P < 0.05). CONCLUSIONS: These results suggest that NE cells in eutopic endometrium probably play some role in the pathogenesis or symptoms of endometriosis.

Reprod Biomed Online. 2009 Oct;19(4):604-9.

Effect of piroxicam administration before embryo transfer on IVF outcome: a randomized controlled trial.

Dal Prato L, Borini A.

Tecnobios Procreazione, Centre for Reproductive Health, Via Dante 15, I-40125 Bologna, Italy.

Two hundred women aged between 28 and 43 years, with infertility from tubal, male, endometriosis or unexplained factor were randomly allocated into treatment (100 patients) and control (100 patients) groups. On the day after oocyte retrieval, each patient began supplementation with progesterone 8% vaginal gel, once daily. The patients in the treatment group received a single oral dose of 10 mg of the non-steroidal anti-inflammatory drug piroxicam 1-2 h before embryo transfer. No statistically significant difference was found between the two groups in any of the analysed endpoints. The rate of positive beta-human chorionic gonadotrophin test per transfer was 37% in the women treated with piroxicam and 47% in controls. The clinical pregnancy rate per transfer and implantation rate were 34% and 19.2% with piroxicam, 38% and 21.9% in controls. The miscarriage rate was 11.8% and 13.2%. No beneficial effect of piroxicam on pregnancy rates was found evaluating either different infertility causes or different ages. This study shows that the administration of a single dose of piroxicam before embryo transfer has no additional effect on pregnancy outcome in patients receiving adequate doses of progesterone for luteal phase supplementation after IVF or ICSI.

Gynecol Endocrinol. 2009 Nov;25(11):757-61.

Chronic pelvic pain: cause, diagnosis and therapy from a gynaecologist’s and an endoscopist’s point of view.

Neis KJ, Neis F.

Frauenärzte am Staden, ETC – European Training Center for Gynecologic Endoscopy and Gynecologic Surgery, Saarbrücken, Germany. etc@gyn-saar.de

Chronic pelvic pain is a significant problem in gynaecology, as the causes often cannot be found by a general gynaecologic examination. Subsequently, the women often consult various physicians without a right and precise diagnosis being made. Thus, it is necessary to find a possibility for how to help these women quickly and effectively. As in nearly 1/3 of the cases the reason for the pain is an endometriosis and in another third, adhesions are responsible for the pain, the biggest part can be diagnosed and treated by laparoscopy. If laparoscopically no reason can be found, it is advisable to send the patient to a psychosomatic physician, who then can start a correspondingly differentiated diagnosis and therapy.

Gynecol Endocrinol. 2009 Nov;25(11):734-40.

Endometriosis in Italy: from cost estimates to new medical treatment.

Luisi S, Lazzeri L, Ciani V, Petraglia F.

Division of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy. luisi@unisi.it

Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induced a chronic inflammatory reaction. The data collected from Italy showed that around 3 million women are affected by endoemtriosis and the condition was predominantly found in women of reproductive age (50% of women were in the 29-39 age range), only 25% of women were asymptomatic. The associated symptoms can create an impact in general physical, mental, and social well-being. Endometriosis is associated with severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, cyclical, or perimenstrual symptoms, with or without abnormal bleeding, infertility, and chronic fatigue. The annual cost for hospital admission can be estimated to be in a total around 54 million euros. The average time for right diagnosis is around 9 years still today and it follows a long and expensive diagnostic search. Therapies can be useful to relieve and sometimes solve the symptoms, encourage fertility, eliminate endometrial lesions, and restore the anatomy of the pelvis. For medical therapy, several different preparations (oral contraceptives, progestogenics, gestrinone, danazol, and GnRHa) and new options (GnRH antagonists, aromatase inhibitors, estrogen receptor beta agoinist, progesterone receptor modulators, angiogenesis inhibitors, and COX-2 selective inhibitors) are available.

Gynecol Endocrinol. 2009 Nov;25(11):717-21.

Endometriosis and in vitro fertilisation: a review.

Dechaud H, Dechanet C, Brunet C, Reyftmann L, Hamamah S, Hedon B.

Department of OB/GYN and Reproductive Medicine, Faculty of Medicine, University Hospital Arnaud de Villeneuve, INSERM 637, University Montpellier I, 34295 Montpellier cedex 5, France. h-dechaud@chu-montpellier.fr

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks.

Gynecol Endocrinol. 2009 Nov;25(11):707-12.

Effect of peritoneal fluid from endometriosis patients on neuroblastoma cells in culture.

Bersinger NA, Brodbeck MH, Jahns B, Mueller MD.

Department of Obstetrics/Gynaecology, University of Berne, Berne, Switzerland. nick.bersinger@dkf.unibe.ch

AIM: Endometriosis is often associated with lower abdominal pain, dysmenorrhea, dyspareunia, and chronic pelvic pain. There is no correlation between the extent of endometriosis and the intensity of pain. The mechanism of pain in endometriosis is unknown. The aim of our study was to investigate the influence of peritoneal fluid (PF) from endometriosis patients on cultured neural cells that are the morphological basis of nociception, and to determine whether there was a relationship between the rAFS staging and an elevation of TGF-beta1 production by these cells. METHODS: Different human neuroblastoma cell lines were grown to 3/4 confluence and then cultured in presence of PF pooled according to the presence of no, mild, or severe endometriosis. After 6 and 24 h of incubation, the morphological changes were assessed and the metabolic activity was determined. RESULTS: The different cell lines showed strongly varying proliferation and aggregation patterns. The metabolic activity was also varying between cell lines, but no consistently increased cell turnover in the PF when compared with the control medium nor associated to a particular, endometriosis-derived PF pool could be shown. In this experimental setting, we have observed that the cell proliferation in the presence of PF was inhibited, and not enhanced as it might have been expected. Measurement of TGF-beta1 showed higher production rates for this cytokine under exposure to PF than in controls for some but not all tested cell lines, but there was no association with the stage (rAFS) of the disease. CONCLUSION: The neuronal cell culture model may become a useful tool to investigate the endometriosis-derived pain, but different endpoints and cell lines may have to be introduced.

Gynecol Endocrinol. 2009;25(12):844-7.

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.

Gynecol Endocrinol. 2009;25(12):765-7.

The value of gonadotropin-releasing hormone-agonists together with other drugs for medical treatment and prevention.

Schindler AE.

Gynecol Endocrinol. 2009 Nov;25(11):762-4.

Minimal endometriosis: a therapeutic dilemma?

Rossmanith WG.

Department of Obstetrics-Gynecology, Diakonissenkrankenhaus Karlsruhe, Academic Teaching Hospital, University of Freiburg, Germany. rossmanith@diak-ka.de

Accidental finding of minimal endometriosis during surgery for complaints unassociated with endometriosis presents a therapeutical dilemma. Because the clinical significance of minimal endometriosis is not thoroughly defined, it is uncertain by which means, if at all, such types of peritoneal or ovarian lesions should be treated. We, therefore, compiled our clinical observations and evaluated them in relation to the results reported in the recent literature. A search on the clinical importance and the need for any treatment of minimal and mild endometriosis was conducted. Based on the available evidence, we are tempted to conclude that minimal endometriosis should be treated surgically when accidentally discovered. This approach should be exerted even in the absence of clinical symptoms. However, postoperative medical treatment is not warranted in those patients who are without clinical complaints. Because the clinical course of minimal endometriosis is not predictable, any benefit from specific medications remains uncertain. When associated with infertility, minimal endometriosis should be surgically erased, thus to allow spontaneous conceptions to occur. As there is no evidence of medical treatment modalities altering the clinical course of minimal and mild endometriosis, any specific medical treatment (i.e. GnRH analogues, danazol) is not indicated in asymptomatic patients and those desiring pregnancy.

Gynecol Endocrinol. 2009 Nov;25(11):751-6.

Progestins and medical treatment of endometriosis – physiology, history and society.

Belaisch J.

Maternité Pinard, Hopital Saint Vincent de Paul, Université René Descartes Paris France. jean.belaisch@wanadoo.fr

The transitory effect of hormonal treatment is the alleged main reason to criticize progestins (PGS) and combined pills (OP) in the managment of endometriosis. To the contrary their poor efficacy in the long run is often underlined. As a result, medical treatment is too seldom advised in endometriosis. In this article, we shall focus on the analysis of the reasons of the paucity of the medical interest given to progestins, reasons, which are not of a scientific or objective nature. The ultimate aim of this analysis is to develop arguments in favour of continuous administration of hormones as to obtain not simply an anovulation but a state of prolonged amenorrhea much more efficacious than the simple suppression of ovulation too often advised. And, with an emphasis on the fundamental role of surgery in the treatment of endometriosis, to give the greatest consideration to the specific nature of this disease, which is a chronic disease, justifying the long duration of hormonal administration.

Gynecol Endocrinol. 2009 Nov;25(11):748-50.

Endometriosis in the north Italian province of South Tyrol.

Steinkasserer M, Engl B.

Department of Obstetrics and Gynaecology, Center for Human Reproductive Medicine, Hospital Bruneck, Spitalstrasse 11, 39031 Italy.

Here, we report regarding the health status and medical support for patients suffering from endometrioisis in South Tyrol, which is a politically autonomous province in the north of Italy containing three different ethnic groups. The health service is administered largely by the autonomous regional government. Because of the establishment of a centre for reproductive medicine and the introduction of laparoscopy as a prime surgery method, the gynaecological department of the hospital in Bruneck developed into a reference centre for diagnosis and surgical treatment for endometriosis. The planned future social, health care and insurance developments on local and national level regarding this illness will be discussed.

Gynecol Endocrinol. 2009 Nov;25(11):741-7.

Expression of the human endogenous retroviruse-W envelope gene syncytin in endometriosis lesions.

Oppelt P, Strick R, Strissel PL, Winzierl K, Beckmann MW, Renner SP.

Department of Gynecology and Obstetrics, University of Erlangen, Erlangen, Germany. Peter.Oppelt@akh.linz.at

BACKGROUND: None of the existing theories provides a satisfactory explanation of the development of endometriosis. One hypothesis that may lead to further clarification is that the expression of specific proteins of human endogenous retroviruses (HERVs) might influence the development of endometriosis lesions. Such endogenous retroviral proteins include syncytin, coded by HERV-W, which is associated with the physiological development of the placenta during pregnancy. This study investigated the influence of HERV-W gene expression in endometriosis foci (EM) quantitatively at the RNA level. MATERIALS AND METHODS: Specific RNA expression of syncytin (HERV-W) was investigated in various endometrial tissues from 42 patients (with normal endometrium, postmenopausal endometrium, EM, and endometrial carcinoma). RNA was isolated from the tissue samples and transcribed into DNA using reverse transcriptase polymerase chain reaction. The resulting DNA fragments were analyzed using agarose gel electrophoresis and assessed quantitatively. RESULTS: Normalized syncytin expression was low in EM. In Histologically normal endometrium from endometriosis patients, the expression of normalized syncytin was seven times higher in comparison with the histologically normal endometrium in the control group. CONCLUSIONS: HERV-W syncytin expression apparently does not play a role in EM. However, it may possibly influence the development of endometriosis because of increased expression in normal endometrium in endometriosis patients.

Gynecol Endocrinol. 2009 Nov;25(11):726-33.

Neurokinin 1 receptor gene polymorphism might be correlated with recurrence rates in endometriosis.

Renner SP, Ekici AB, Maihöfner C, Oppelt P, Thiel FC, Schrauder M, Uenluehan N, Bani MR, Strissel PL, Strick R, Beckmann MW, Fasching PA.

Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.

INTRODUCTION: Dysmenorrhoea is the major symptom in women with endometriosis. Recently, pain modulation through Neurokinin-1-receptor (NK1R) pathways have been investigated in neuropathic pain patients. Aim of this study was, therefore, to examine the effect of a single nucleotide polymorphism (SNP) of the NK1R gene on the susceptibility for endometriosis and the disease free survival (DFS) after surgery for endometriosis. MATERIAL AND METHODS: A case-control study was conducted and germline DNA was isolated. Patients were followed up for a recurrence of the disease up to 4 years. Case-control analyses were performed for parameters of the medical history and the genotype of the NK1R-SNP rs881. Furthermore, DFS probabilities were calculated. RESULTS: Concerning the DFS preoperative pain levels and the NK1R genotype were independent predictors for a recurrence with hazard ratios of 2.55 (95% CI: 1.32-4.95) for patients with a high preoperative pain level and 0.44 for patients with a heterozygous or homozygous variant genotype in rs881 (95% CI: 0.21-0.88). CONCLUSION: The polymorphism rs811 seems to be associated with a lower recurrence risk in endometriosis patients. Thus, there might be a clinical relevant role of the NK1 pathway in the pain perception of endometriosis patients.

Gynecol Endocrinol. 2009 Nov;25(11):722-5.

Impact of endometriosis on quality of life: a pilot study.

Oehmke F, Weyand J, Hackethal A, Konrad L, Omwandho C, Tinneberg HR.

Department of Obstetrics and Gynecology, Justus Liebig University of Giessen, Giessen, Germany.

Endometriosis affects 6-10% of women in reproductive age, 35-50% of whom experience pain, infertility or both. Mild cases are managed medically but surgery provides relief to women in pain. However, symptoms recur in 75% of cases within 2 years. We investigated the impact of endometriosis on quality of life among 65 women aged 18-60 years working at a city supermarket in Giessen, Germany. Of the 65 women, 12 had undergone surgeries, 22 had dysmenorrhoea, 24 dyspareunia and 3 were infertile. Of the 22 women with dysmenorrhoea, 10 had difficulties performing gardening, housework, sports and leisure activities. Five of these 10 women experienced social isolation, 6 professional setbacks; 6 declined efficiency at work and 3 had taken time off work. Of the 24 women with dyspareunia, 7 experienced minimal, 12 light and 5 moderate to strong pain. Only 16 of these 24 women discussed the problem with their partners. This study demonstrates that pain is a major cause of physical, psycho-social, emotional and professional or work related impairment among women with endometriosis. Because endometriosis is likely to impose emotional and financial burdens, we suggest that future studies should be extended to include interviews with family members.

Gynecol Endocrinol. 2009 Nov;25(11):713-6.

Anti muellerian hormone serum levels in women with endometriosis: a case-control study.

Shebl O, Ebner T, Sommergruber M, Sir A, Tews G.

Department of Obstetrics and Gynecology, IVF-Unit, Landesfrauen- und Kinderklinik, Linz, Austria. omar.shebl@gespag.at

OBJECTIVE: To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis. DESIGN: A case-control study SETTING: Women’s General Hospital, Linz, Austria. PATIENT(S): Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group). INTERVENTIONS: None. MAIN OUTCOME MEASURES: AMH serum level. RESULTS: Mean AMH serum level was significantly lower in the study than in the control group (2.75 + or – 2.0 ng/ml vs. 3.46 + or – 2.30 ng/ml, p < 0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28 + or – 1.93 ng/ml vs. 3.44 + or – 2.06 ng/ml; p = 0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38 + or – 1.83 ng/ml vs. 3.58 + or – 2.46 ng/ml; p < 0.0001). CONCLUSION: Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.

Gynecol Endocrinol. 2009 Nov;25(11):701-6.

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis.

Scholl B, Bersinger NA, Kuhn A, Mueller MD.

Department of Obstetrics/Gynaecology and Department of Clinical Research, University of Berne, Berne, Switzerland.

Endometriosis affects 10-20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-alpha (TNF-alpha), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-alpha and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-alpha and glycodelin when compared with the other patients (no or moderate pain). TNF-alpha and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.

Gynecol Endocrinol. 2009 Nov;25(11):694-700.

Endometriosis in Hungary.

Szendei GA.

Faculty of Medicine, Division of Endocrinology and Endometriosis, First Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Baross u. 27., Hungary. szendei@noi1.sote.hu

Endometriosis is a growing healthcare problem all around the world. I discuss in this article how the hungarian healthcare system is working and helping patients suffering from endometriosis. I discuss all diagnostic and therapeutic possibilities which are available for the patients. I discuss also some data from my own practice, 181 patients suffering from chronic pelvic pain caused by endometriosis.

Gynecol Endocrinol. 2009 Nov;25(11):693.

Endometriosis–a European perspective.

Schindler AE, Druckmann R.

Endometriosis Research Foundation.

Epidemiology. 2010 Jan;21(1):16-23.

Adult physical activity and endometriosis risk.

Vitonis AF, Hankinson SE, Hornstein MD, Missmer SA.

Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. avitonis@partners.org

BACKGROUND: Regular exercise has been associated with a 40%-80% reduction in risk for endometriosis in several case-control studies. However, women experiencing symptoms prior to their diagnosis may be less likely to exercise than healthy controls, thus biasing the observed association. METHODS: Using data collected from the Nurses’ Health Study II, a prospective cohort study of premenopausal US nurses that began in 1989, we have attempted to clarify this relation. Data are updated every 2 years with follow-up for these analyses through 2001. In 1989, 1991, and 1997 women reported average amount of time per week engaging in various physical activities. A metabolic equivalent (MET) score was assigned to each activity, and these were summed to estimate total activity. RESULTS: A total of 102,197 premenopausal women contributed 996,422 person-years of follow-up with 2703 cases of laparoscopically confirmed endometriosis. After adjusting for BMI at age 18, current BMI, smoking, parity, infertility status, oral contraceptive use, age at menarche, and menstrual cycle length and pattern in college, we observed only a slight reduction in the incidence of endometriosis, comparing the highest level of activity (>or=42 MET hours/week) to the lowest (<3 MET hours/week) (rate ratio = 0.89 [95% confidence interval = 0.77-1.03]). The association was limited to participants with no past or concurrent infertility (P = 0.002, test for heterogeneity). No associations were seen with inactivity. CONCLUSIONS: In this first prospective assessment, we did not find evidence of the strong inverse association previously reported, although we cannot rule out a modest inverse association.

Acta Obstet Gynecol Scand. 2009;88(12):1402-10.

Costs and health-related quality of life effects of hysterectomy in patients with benign uterine disorders.

Taipale K, Leminen A, Räsänen P, Heikkilä A, Tapper AM, Sintonen H, Roine RP.

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.

OBJECTIVE: To gain knowledge about the utility of hysterectomy in a real-world setting and to relate the utility of the intervention to its costs. DESIGN: Prospective observational study. SETTING: University referral hospital in Helsinki. POPULATION: A total of 337 women entering for routine hysterectomy due to a benign disease (210 benign uterine or ovarian cause, 20 endometriosis, 51 uterovaginal prolapse, 56 menorrhagia). METHODS: Patients filled in the 15D health-related quality of life (HRQoL) questionnaire before and six months after the operation. Costs were examined from the perspective of secondary care provider. Benefits of surgery were extrapolated till the end of remaining statistical life expectancy of each woman in the prolapse group and until menopause in the other groups. MAIN OUTCOME MEASURES: HRQoL and cost per quality-adjusted life year (QALY) gained. RESULTS: Mean [standard deviation (SD)] HRQoL score (on a 0-1 scale) in the whole group improved from the preoperative of 0.905 (0.073) to 0.925 (0.077) six months after the operation (p < 0.001). The largest mean (SD) improvement was seen in patients with endometriosis [0.048 (0.067)] followed by those with menorrhagia [0.024 (0.054)], benign uterine or ovarian cause [0.018 (0.071)], and prolapse [0.017 (0.055)]. In the whole group, the intervention produced a mean (SD) of 0.222 (1.270) QALYs at mean (SD) direct hospital cost of euro3,138 (2,098). Consequently, the cost per QALY gained in the whole group was euro14,135 varying from euro3,720 to 31,570 in the disease groups. CONCLUSIONS: The cost per QALY gained for hysterectomy for benign uterine disorders is strongly dependent on the indication for surgery.

Mod Pathol. 2010 Jan;23(1):38-44. Epub 2009 Nov 6.

Cadherin expression in gastrointestinal tract endometriosis: possible role in deep tissue invasion and development of malignancy.

Van Patten K, Parkash V, Jain D.

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.

Cadherins are cell surface proteins crucial for cell adhesion and tissue integrity. The mechanism of deep tissue invasion in gastrointestinal endometriosis is unknown and may be related to the altered expression of these cell surface proteins. The goal of this study was to evaluate the expression of N-cadherin, E-cadherin, and beta-catenin in peritoneal endometriotic implants, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis. Cases of peritoneal endometriosis, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis were identified from our pathology database. Immunohistochemistry was performed using antibodies against N-cadherin, E-cadherin, and beta-catenin on representative tissue sections. Cases of normal proliferative and secretory endometrium and adenomyosis were included in the study for comparison. The intensity and extent of staining for each marker was scored semiquantitatively. Appropriate positive and negative controls were used. A total of 38 cases (peritoneal endometriosis (n=14), gastrointestinal endometriosis (n=21: 11 colon, 8 appendix, 2 small bowel), and 3 cases of endometrioid carcinoma arising in colonic endometriosis (n=3)) were included in the study. Compared with normal proliferative endometrium, N-cadherin expression was decreased in intensity and extent in secretory endometrium. Peritoneal and gastrointestinal endometriosis also showed markedly decreased expression of N-cadherin compared with proliferative endometrium. All three cases of carcinoma arising in colonic endometriosis showed a total loss of N-cadherin in the tumor, but preserved E-cadherin and beta-catenin expression. In these cases, areas of benign endometriotic glands near the tumor showed weak and focal N-cadherin expression that was gradually lost. Moderate-to-strong membranous staining for beta-catenin expression and variable intensity of E-cadherin expression was seen diffusely in normal endometrium and all study cases. These results strongly suggest that alterations of N-cadherin expression in gastrointestinal endometriosis may have an important role in the mechanism that underlies deep tissue invasion, and possibly also in the development of malignancy.

Hum Reprod. 2010 Feb;25(2):462-9. Epub 2009 Nov 7.

Induction of a local pseudo-pregnancy via levonorgestrel-loaded microspheres for the treatment of endometriosis in a rabbit model.

Yuan P, Huang Y, Wu H, Teng Z, Zhang J, Xin X.

Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi’an, Shaan’xi 710032, China. ypfmmu@gmail.com

BACKGROUND: Endometriosis is a chronic disease that responds to systemic pseudo-pregnancy therapy. However, side effects limit their long-term use, and recurrence often occurs after cessation of medication. Reducing side effects whereas improving therapeutic efficacy of pseudo-pregnancy therapy seems contradictory, but appealing. In order to address this dilemma, the efficacy and side effects of local pseudo-pregnancy therapy were investigated for the first time in an endometriosis animal model. METHODS AND RESULTS: Levonorgestrel-loaded polylactic acid microspheres (LNG-microspheres) were prepared by using an oil-in-water emulsification-solvent evaporation method. Rabbits with experimental endometriosis were randomized to treatment with local pseudo-pregnancy therapy, local blank microspheres, systemic pseudo-pregnancy therapy, ovariectomy or the control. Local pseudo-pregnancy was induced by injection of LNG-microspheres directly into endometrial cysts. Compared with the systemic pseudo-pregnancy group, significantly higher intra-cystic drug levels were maintained for at least 6 months with much lower serum levels in the local pseudo-pregnancy group (P < 0.01). The high intra-cystic levonorgestrel simulated a state of potent pregnancy, which induced size reductions and endometrial atrophy comparable to those of ovariectomy. Moreover, major metabolic parameters and ovarian function were not disturbed by local pseudo-pregnancy therapy. CONCLUSIONS: Induction of a local pseudo-pregnancy could achieve therapeutic efficacy comparable to that of ovariectomy without provoking any marked side effects in a rabbit endometriosis model. Thus it may be a preferable option for patients with endometriosis.

Hum Reprod. 2010 Jan;25(1):265-74. Epub 2009 Nov 7.

Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia.

Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, Talbot JM, Baker HW.

Department of Obstetrics and Gynaecology, Monash University, Level 5, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168 Australia. david.healy@med.monash.edu.au

BACKGROUND: Obstetric haemorrhages have been reported to be increased after assisted reproduction technologies (ART) but the mechanisms involved are unclear. METHODS: This retrospective cohort study compared the prevalence of antepartum haemorrhage (APH), placenta praevia (PP), placental abruption (PA) and primary post-partum haemorrhage (PPH) in women with singleton births between 1991 and 2004 in Victoria Australia: 6730 after IVF/ICSI, 24 619 from the general population, 779 after gamete intrafallopian transfer (GIFT) and 2167 non-ART conceptions in infertile patients. Risk factors for haemorrhages in the IVF/ICSI group were examined by logistic regression. RESULTS: The IVF/ICSI group had more APH: 6.7 versus 3.6% (adjusted OR 2.0; 95% CI 1.8-2.3), PP: 2.6 versus 1.1% (2.3; 1.9-2.9), PA: 0.9 versus 0.4% (2.1; 1.4-3.0) and PPH: 11.1 versus 7.9% (1.3; 1.2-1.4) than the general population. APH, PP and PA were as frequent in the GIFT group as in the IVF/ICSI group, but were less frequent in the non-ART group. Within the IVF/ICSI group, fresh compared with frozen thawed embryo transfers (FET) was associated with more frequent APH (1.5; 1.2-1.8) and PA (2.1; 1.2-3.7) and the odds ratio increased with number of oocytes collected (1.02; 1.00-1.04). Endometriosis patients had more PP (1.7; 1.2-2.4) and PPH (1.3; 1.1-1.6) than those without endometriosis. FET in artificial cycles was associated with increased PPH (1.8; 1.3-2.6) compared with FET in natural cycles. CONCLUSIONS: Obstetric haemorrhages are more frequent with singleton births after IVF, ICSI and GIFT. The exploratory analysis of factors in the IVF/ICSI group, showing associations with fresh embryo transfers in stimulated cycles, endometriosis and hormone treatments, suggests that events around the time of implantation may be responsible and that suboptimal endometrial function is the critical mechanism.

Eur J Obstet Gynecol Reprod Biol. 2010 Feb;148(2):204-5. Epub 2009 Nov 5.

Intra-abdominal hemorrhage due to previously unknown endometriosis in the third trimester of pregnancy with uneventful neonatal outcome: a case report.

Grunewald C, Jördens A.

Mol Hum Reprod. 2010 Mar;16(3):207-14. Epub 2009 Nov 5.

Genetic association of phase I and phase II detoxification genes with recurrent miscarriages among North Indian women.

Parveen F, Faridi RM, Das V, Tripathi G, Agrawal S.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP 226014, India.

Allelic variants of the detoxification genes that have impaired biotransformation functions may increase susceptibility to reproductive toxicity leading to endometriosis, recurrent miscarriage (RM) or poor pregnancy outcome. In the present study, we have investigated CYP1A1, CYP2D6, GSTT1, GSTP1 and GSTM1, which are involved in the phase I and phase II detoxification systems, in relation to their role in the etiology of unexplained RMs. In a case-control study, we have investigated 200 females with RM and 300 age and ethnically matched healthy controls with successful reproductive history from North India. The frequencies of phase I wild-type genotypes of CYP1A1 and CYP2D6 in RM cases were 0.56 and 0.60, whereas in controls these were 0.68 and 0.65, respectively (both P < 0.05). The GSTM1 null-genotype frequencies were 0.66 and 0.84 among RM cases and controls, respectively, the GSTT1 null-genotype frequencies were 0.52 and 0.45 (P < 0.005) and the GSTP1 variant allele frequencies were 0.23 and 0.20, respectively. In conclusion, we observed significant protective effects of phase I wild-type genotypes and association of the GSTT1 null genotype with RM. Through combined analyses we have highlighted the importance of the balance of phase I/phase II detoxification systems, in the etiology of RM.

Hum Reprod. 2010 Jan;25(1):101-9. Epub 2009 Nov 5.

Role of TGF-betas in normal human endometrium and endometriosis.

Omwandho CO, Konrad L, Halis G, Oehmke F, Tinneberg HR.

Department of Biochemistry, University of Nairobi, Nairobi, Kenya.

Endometriosis is characterized by presence of endometrial tissue outside the uterus. Prevalence is estimated at 6-10% in the general female population and many patients experience pain and/or infertility. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of viable endometriotic tissue. Mild cases are managed medically with contraceptive steroids and non-steroidal anti-inflammatory agents. Surgery provides relief to women in pain but symptoms recur in 75% of cases within 2 years. Starting with menstruation, we have categorized endometriosis into six stages, namely (1) shedding of cells, (2) cell survival, (3) escape from immune surveillance, (4) adhesion to peritoneum, (5) angiogenesis and (6) bleeding. In most of these biological processes, which resemble metastasis, transforming growth factor-beta (TGF-betas) and their high-affinity receptors are involved directly or indirectly. TGF-betas are abundantly and differentially expressed in the endometrium under hormonal control. Although they are preferentially synthesized in the stroma, glands and macrophages also secrete TGF-betas into the uterine fluid, where interaction with preimplantation embryos is suspected. Because mRNA and protein expression of all three TGF-betas is increased around menstruation, we suggest that TGF-betas might be involved in initiation of menstruation. Furthermore, because of high postmenstrual TGF-beta3 levels, we suppose that it might participate in scarless postmenstrual regeneration of endometrium. Our suggestions pave the way to novel routes of investigation into the roles of TGF-betas during menstruation and endometriosis.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):21-5. Epub 2009 Nov 4.

Peritoneal vascular density assessment using narrow-band imaging and vascular analysis software, and cytokine analysis in women with and without endometriosis.

Kuroda K, Kitade M, Kikuchi I, Kumakiri J, Matsuoka S, Kuroda M, Takeda S.

Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan. arthur@juntendo.ac.jp

The development and onset of endometriosis is associated with angiogenesis and angiogenic factors including cytokines. We analyzed intrapelvic conditions in women with endometriosis via vascular density assessment of grossly normal peritoneum and determination of cytokine levels in peritoneal fluid. Seventy-three patients underwent laparoscopic surgery because of gynecologic disease including endometriosis in our department using a narrow-band imaging system. Each patient was analyzed for peritoneal vascular density using commercially available vascular analysis software (SolemioENDO ProStudy; Olympus Corp, Tokyo, Japan). Each patient was also subjected to analysis of interleukin 6 (IL-6), IL-8, tumor necrosis factor-alpha, and vascular endothelial growth factor concentrations in peritoneal fluid. We defined 4 groups as follows: group 1, endometriosis: gonadotropin-releasing hormone (GnRH) agonist administration group (n=27); group 2, endometriosis: GnRH agonist nonadministration group (n=15); group 3, no endometriosis: GnRH agonist administration group (n=18); and group 4, no endometriosis: GnRH agonist nonadministration group (n=13). No significant differences in peritoneal vascular density between the 4 groups were found under conventional light; however, under narrow-band light, vascular density in the endometriosis groups (groups 1 and 2) was significantly higher. Cytokine analysis of the 4 groups determined that IL-6 and IL-8 concentrations were significantly higher compared with the no endometriosis groups (groups 3 and 4). Tumor necrosis factor-alpha and vascular endothelial growth factor concentrations were not significantly different between groups. In endometriosis, peritoneal vascular density was significantly higher as assessed using the narrow-band imaging system and SolemioENDO ProStudy, whereas GnRH agonist did not obviously decrease vascular density but IL-6 concentration was lower in the GnRH agonist administration group. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Am J Phys Anthropol. 2009;140 Suppl 49:137-54.

Reproductive ecology and the endometrium: physiology, variation, and new directions.

Clancy KB.

Department of Anthropology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA. kclancy@illinois.edu

Endometrial function is often overlooked in the study of fertility in reproductive ecology, but it is crucial to implantation and the support of a successful pregnancy. Human female reproductive physiology can handle substantial energy demands that include the production of fecund cycles, ovulation, fertilization, placentation, a 9-month gestation, and often several years of lactation. The particular morphology of the human endometrium as well as our relative copiousness of menstruation and large neonatal size suggests that endometrial function has more resources allocated to it than many other primates. The human endometrium has a particularly invasive kind of hemochorial placentation and trophoblast that maximizes surface area and maternal-fetal contact, yet these processes are actually less efficient than the placentation of some of our primate relatives. The human endometrium and its associated processes appear to prioritize maximizing the transmission of oxygen and glucose to the fetus over efficiency and protection of maternal resources. Ovarian function controls many aspects of endometrial function and thus variation in the endometrium is often a reflection of ecological factors that impact the ovaries. However, preliminary evidence and literature from populations of different reproductive states, ages and pathologies also suggests that ecological stress plays a role in endometrial variation, different from or even independent of ovarian function. Immune stress and psychosocial stress appear to play some role in the endometrium’s ability to carry a fetus through the mechanism of inflammation. Thus, within reproductive ecology we should move towards a model of women’s fecundity and fertility that includes many components of ecological stress and their effects not only on the ovaries, but on processes related to endometrial function. Greater attention on the endometrium may aid in unraveling several issues in hominoid and specifically human evolutionary biology: a low implantation rate, high rates of early pregnancy loss, prenatal investment in singletons but postnatal support of several dependent offspring at once, and higher rate of reproductive and pregnancy-related pathology compared to other primates, ranging from endometriosis to preeclampsia. The study of the endometrium may also complicate some of these issues, as it raises the question of why humans have a maximally invasive placentation method and yet slow fetal growth rates. In this review, I will describe endometrial physiology, methods of measurement, variation, and some of the ecological variables that likely produce variation and pregnancy losses to demonstrate the necessity of further study. I propose several basic avenues of study that leave room for testable hypotheses in the field of reproductive ecology. And finally, I describe the potential of this work not just in reproductive ecology, but in the resolution of broader women’s health issues. Copyright 2009 Wiley-Liss, Inc.

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