Fertil Steril. 2009 Oct;92(4):1497.e9-12. Epub 2009 Aug 22.

Patient with pelvic pains: retroperitoneal fibrosis or pelvic endometriosis? A case report and review of literature.

Pezzuto A, Pomini P, Steinkasserer M, Nardelli GB, Minelli L.

Center for Reproductive Medicine, Department of Obstetrics, Gynecology, and Neonatology, University of Parma, Parma, Italy.

OBJECTIVE: To describe how a hydronephrosis can lead to a difficult differential diagnosis between endometriosis and retroperitoneal fibrosis. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Sacro Cuore Don Calabria General Hospital, Negrar, Verona, Italy. PATIENT(S): The history of a 34-year-old woman revealed the appearance of hydroureteronephrosis on the right side at the 35th week of pregnancy. She had an magnetic resonance imaging scan and was diagnosed with a spread retroperitoneal fibrosis. After 2 months, the patient reported the occurrence of pelvic pain, dyspareunia and dysmenorrhea. She was treated with corticosteroids and tamoxifen with no results. INTERVENTION(S): Laparoscopic surgery. A complete retroperitoneal extirpation was done of an endometriotic nodule of the right broad ligament, near the right ureter (without stenosis). MAIN OUTCOME MEASURE(S): Reduction of pelvic pain. RESULT(S): She noticed an important decrease of pain. CONCLUSION(S): The cause of hydronephrosis could be a physiologic hydroureteronephrosis, which is the most common cause of dilatation of the urinary tract in pregnancy. The pain symptoms of the patients seemed to be linked to endometriosis and not to retroperitoneal fibrosis. Magnetic resonance imaging sometimes does not enable a correct diagnosis between these two pathologies. Fertile women with suspected fibrosis should undergo a diagnostic laparoscopy by an expert surgeon in retroperitoneal surgery.

Med Hypotheses. 2009 Aug 20. [Epub ahead of print]

Induction of a local pseudo-pregnancy for the treatment of endometriosis.

Yuan P, Huang Y, Cheng B, 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.

As a common cause of chronic pelvic pain, endometriosis affects 10% of women of reproductive age. The most popular strategy for treating endometriosis is pseudo-pregnancy therapy. However, the efficacy of common systemic pseudo-pregnancy therapy is significantly attenuated by poor compliance because of so many side effects. While levonorgestrel-releasing intrauterine systems (LNG-IUS) successfully localize the effect of pseudo-pregnancy to the genital tract in treating endometriosis, it seemed to be insufficient to suppress the ovarian and extragenital endometriosis. We postulate that induction of a local pseudo-pregnancy via progestogen-loaded microsphere in the lesions of endometriosis may provide a more effective treatment with fewer side effects.

Soc Sci Med. 2009 Oct;69(8):1220-7. Epub 2009 Aug 21.

The etiquette of endometriosis: stigmatisation, menstrual concealment and the diagnostic delay.

Seear K.

Monash University, Sociology, School of Political and Social Inquiry, Victoria 3800, Australia. kate.seear@arts.monash.edu.au

Endometriosis is a chronic gynaecological condition of uncertain aetiology characterised by menstrual irregularities. Several studies have previously identified a lengthy delay experienced by patients between the first onset of symptoms and eventual diagnosis. Various explanations have been advanced for the diagnostic delay, with both doctors and women being implicated. Such explanations include that doctors normalise women’s menstrual pain and that women might delay in seeking medical advice because they have difficulty distinguishing between ‘normal’ and ‘abnormal’ menstruation. It has been suggested that the diagnostic delay could be reduced if women were trained in how to distinguish between ‘normal’ and ‘abnormal’ menstrual cycles. In this paper I argue that whilst these may be factors in the diagnostic delay, women’s reluctance to disclose problems associated with their menstrual cycle may be a more significant and hitherto neglected factor. I argue women are reluctant to disclose menstrual irregularities because menstruation is a ‘discrediting attribute’ (Goffman, 1963) and disclosure renders women vulnerable to stigmatisation. Women actively conceal their menstrual irregularities through practices of the ‘menstrual etiquette’ (Laws, 1990) which involves the strategic concealment of menstrual problems. This argument is supported through an analysis of the experiences of 20 Australian women diagnosed with endometriosis. The ramifications of this analysis for chronic pain conditions more generally and for practical strategies designed to address the endometriosis diagnostic delay are considered.

Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):415-8.

Bowel resection for severe endometriosis: an Australian series of 177 cases.

Wills HJ, Reid GD, Cooper MJ, Tsaltas J, Morgan M, Woods RJ.

Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

BACKGROUND: Colorectal resection for severe endometriosis has been increasingly described in the literature over the last 20 years. AIMS: To describe the experiences of three gynaecological surgeons who perform radical surgery for colorectal endometriosis. METHODS: The records of three surgeons were reviewed. Relevant information was extracted and complied into a database. RESULTS: One hundred and seventy-seven women were identified as having undergone surgery between February 1997 and October 2007. The primary reason for presentation was pain in the majority of women (79%). Eighty-one segmental resections were performed, 71 disc excisions, ten appendicectomies and multiple procedures in ten women. The majority of procedures (81.4%) were performed laparoscopically. Histology confirmed the presence of disease in 98.3% of cases. A further 124 procedures to remove other sites of endometriosis were conducted, along with an additional 44 procedures not primarily for endometriosis. A total of 16 unintended events occurred. CONCLUSIONS: Our study adds to the growing body of literature describing colorectal resection for severe endometriosis. Overall, the surgery appeared to be well tolerated, demonstrating the role for this surgery.

Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):411-4.

Relevance of gastrointestinal symptoms in endometriosis.

Maroun P, Cooper MJ, Reid GD, Keirse MJ.

Department of Endogynaecology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. paulette@paulettemaroun.com.au

BACKGROUND: Endometriosis commonly presents with a range of symptoms none of which are particularly specific for the condition, often resulting in misdiagnosis or delay in diagnosis. AIM: To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms. METHODS: Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis. RESULTS: Endometriosis was confirmed by histology in 290 women (84.5%). Bowel lesions were present in only 7.6%. Ninety per cent of women had gastrointestinal symptoms, of which bloating was the most common (82.8%), but 71.3% also had other bowel symptoms. All gastrointestinal symptoms were similarly predictive of histologically confirmed endometriosis. Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed. CONCLUSION: Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.

Am J Reprod Immunol. 2009 Sep;62(3):187-95.

Plasma C3a-des-Arg levels in women with and without endometriosis.

Fassbender A, D’Hooghe T, Mihalyi A, Kyama C, Simsa P, Lessey BA.

Leuven University Fertility Centre, Department of Obstetrics & Gynecology, University Hospital Gasthuisberg, Leuven, Belgium.

PROBLEM: The lack of a reliable method for early non-invasive detection of endometriosis often results in delayed diagnosis. The aim of this study was to test the hypothesis that the plasma concentration of complement factor C3a (anaphylatoxin) can be used as a non-invasive test in the diagnosis of endometriosis. METHOD OF STUDY: The C3a concentration was analyzed using ELISA in 160 patients with (n = 109) or without (n = 51) endometriosis during menstruation (n = 49), follicular phase (n = 55), and luteal (n = 56) phase. RESULTS: Plasma C3a concentration was comparable between patients with [102 (27-2213) ng/mL] and without [105 (32-2340) ng/mL] (P = 0.84) endometriosis, also when assessed separately during menstruation, follicular phase, and luteal phase. CONCLUSION: We found no difference in C3a levels between women with and without endometriosis and did not confirm our hypothesis that plasma C3a levels can be used as diagnostic test for endometriosis.

Am J Reprod Immunol. 2009 Sep;62(3):128-38.

Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

Kim JY, Lee DH, Joo JK, Jin JO, Wang JW, Hong YS, Kwak JY, Lee KS.

Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan, Korea.

PROBLEM: Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. METHOD OF STUDY: Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. RESULTS: The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P < 0.001), CD4(+) T cells (R = 0.93, P < 0.001), and monocytes (R = 0.70, P = 0.01). Moreover, the addition of ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. CONCLUSION: These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

Mol Hum Reprod. 2009 Oct;15(10):625-31. Epub 2009 Aug 19.

MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis.

Burney RO, Hamilton AE, Aghajanova L, Vo KC, Nezhat CN, Lessey BA, Giudice LC.

Division of Reproductive Endocrinology and Infertility, Madigan Army Medical Center, Tacoma, WA, USA.

Endometriosis is a common gynecologic disorder characterized by pain and infertility. In addition to estrogen dependence, progesterone resistance is an emerging feature of this disorder. Specifically, a delayed transition from the proliferative to secretory phase as evidenced by dysregulation of progesterone target genes and maintenance of a proliferative molecular fingerprint in the early secretory endometrium (ESE) has been reported. MicroRNAs (miRNAs) are small noncoding RNAs that collectively represent a novel class of regulators of gene expression. In an effort to investigate further the observed progesterone resistance in the ESE of women with endometriosis, we conducted array-based, global miRNA profiling. We report distinct miRNA expression profiles in the ESE of women with versus without endometriosis in a subset of samples previously used in global gene expression analysis. Specifically, the miR-9 and miR-34 miRNA families evidenced dysregulation. Integration of the miRNA and gene expression profiles provides unique insights into the molecular basis of this enigmatic disorder and, possibly, the regulation of the proliferative phenotype during the early secretory phase of the menstrual cycle in affected women.

Mol Med. 2009 Aug 17. [Epub ahead of print]

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues.

Forte A, Schettino MT, Finicelli M, Cipollaro M, Colacurci N, Cobellis L, Galderisi U.

Departments of Experimental Medicine.

Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue outside of the uterus and with mixed traits of benign and malignant pathology.This study aimed at analysing in endometrial and endometriotic tissues the differential expression of a panel of genes involved in preservation of stemness status and consequently considered as markers of stem cell presence.The expression profiles of a panel of 13 genes (SOX2, SOX15, ERAS, SALL4, OCT4, NANOG, UTF1, DPPA2, BMI1, GDF3, ZFP42, KLF4, TCL1) were analysed by RT-PCR in human endometriotic (n=12) and endometrial samples (n=14). The expression of SALL4 and OCT4 was further analysed by immunohistochemistry.Genes UTF1, TCL1 and ZFP42 showed a trend for higher frequency of expression in endometriosis than in endometrium (p<0.05 for UTF1), while GDF3 showed an higher frequency of expression in endometrial samples. Immunohistochemical analysis revealed that SALL4 was expressed in endometriotic samples but not in endometrium, despite the expression of the corresponding mRNA in both the sample groups.This study highlights a differential expression of stemness-related genes in ectopic and eutopic endometrium and suggests a possible role of SALL4-positive cells in the pathogenesis of endometriosis.

Hum Reprod. 2009 Aug 18. [Epub ahead of print]

Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study.

Al-Jefout M, Dezarnaulds G, Cooper M, Tokushige N, Luscombe GM, Markham R, Fraser IS.

Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia.

BACKGROUND Diagnosis of endometriosis currently requires a laparoscopy and this need probably contributes to the considerable average delay in diagnosis. We have reported the presence of nerve fibres in the functional layer of endometrium in women with endometriosis, which could be used as a diagnostic test. Our aim was to assess efficacy of nerve fibre detection in endometrial biopsy for making a diagnosis of endometriosis in a double-blind comparison with expert diagnostic laparoscopy. METHODS Endometrial biopsies, with immunohistochemical nerve fibre detection using protein gene product 9.5 as marker, taken from 99 consecutive women presenting with pelvic pain and/or infertility undergoing diagnostic laparoscopy by experienced gynaecologic laparoscopists, were compared with surgical diagnosis. RESULTS In women with laparoscopic diagnosis of endometriosis (n = 64) the mean nerve fibre density in the functional layer of the endometrial biopsy was 2.7 nerve fibres per mm(2) (+/-3.5 SD). Only one woman with endometriosis had no detectable nerve fibres. Six women had endometrial nerve fibres but no active endometriosis seen at laparoscopy. The specificity and sensitivity were 83 and 98%, respectively, positive predictive value was 91% and negative predictive value was 96%. Nerve fibre density did not differ between different menstrual cycle phases. Women with endometriosis and pain symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 and 0.8 nerve fibre per mm(2), respectively, P = 0.005). CONCLUSIONS Endometrial biopsy, with detection of nerve fibres, provided a reliability of diagnosis of endometriosis which is close to the accuracy of laparoscopic assessment by experienced gynaecological laparoscopists. This study was registered with the Australian Clinical Trials Registry (ACTR) 00082242 (registered: 12/12/2007). The study was approved by the Ethics Review Committee (RPAH Zone) of the Sydney South West Area Health Service (Protocol number X05-0345) and The University of Sydney Human Research Ethics Committee (Ref. No. 10761) and all women gave their informed consent for participation.

Hum Reprod. 2009 Aug 18. [Epub ahead of print]

Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis.

Bokor A, Kyama CM, Vercruysse L, Fassbender A, Gevaert O, Vodolazkaia A, De Moor B, Fülöp V, D’Hooghe T.

Experimental Laboratory for Gynaecology, Department of Obstetrics and Gynaecology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.

BACKGROUND The aim of our study was to test the hypothesis that multiple-sensory small-diameter nerve fibres are present in a higher density in endometrium from patients with endometriosis when compared with women with a normal pelvis, enabling the development of a semi-invasive diagnostic test for minimal-mild endometriosis. METHODS Secretory phase endometrium samples (n = 40), obtained from women with laparoscopically/histologically confirmed minimal-mild endometriosis (n = 20) and from women with a normal pelvis (n = 20) were selected from the biobank at the Leuven University Fertility Centre. Immunohistochemistry was performed to localize neural markers for sensory C, Adelta, adrenergic and cholinergic nerve fibres in the functional layer of the endometrium. Sections were immunostained with anti-human protein gene product 9.5 (PGP9.5), anti-neurofilament protein, anti-substance P (SP), anti-vasoactive intestinal peptide (VIP), anti-neuropeptide Y and anti-calcitonine gene-related polypeptide. Statistical analysis was done using the Mann-Whitney U-test, receiver operator characteristic analysis, stepwise logistic regression and least-squares support vector machines. RESULTS The density of small nerve fibres was approximately 14 times higher in endometrium from patients with minimal-mild endometriosis (1.96 +/- 2.73) when compared with women with a normal pelvis (0.14 +/- 0.46, P < 0.0001). CONCLUSIONS The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal-mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.

Aust N Z J Public Health. 2009 Aug;33(4):358-64.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women’s Health.

Herbert DL, Lucke JC, Dobson AJ.

School of Population Health, The University of Queensland. d.herbert@sph.uq.edu.au

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women’s Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Clin Exp Obstet Gynecol. 2009;36(2):123-5.

Successful long-term management of adenomyosis associated with deep thrombosis by low-dose gonadotropin-releasing hormone agonist therapy.

Akira S, Iwasaki N, Ichikawa M, Mine K, Kuwabara Y, Takeshita T, Tajima H.

Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan. s-akira@nms.ac.jp

We report the case of a patient with adenomyosis complicated by deep vein thrombosis in whom low-dose gonadotropin-releasing hormone agonist (GnRHa) therapy was useful as a uterus-conserving therapeutic option. The patient was a 34-year-old nulliparous woman who presented with edema and pain in the left lower leg. The patient had been treated with four cycles of GnRHa therapy for adenomyosis and repeatedly experienced chronic pelvic pain, dysmenorrhea and anemia due to hypermenorrhea. Leg venography confirmed deep vein thrombosis, and thrombolytic therapy was performed to eliminate symptoms. Because the patient strongly wanted to conserve the uterus, low-dose GnRHa therapy was initiated. The patient is currently taking 450 microg/day buserelin acetate nasally (regular dose: 900 microg/day), and estradiol levels have been maintained at 24-50 pg/ml. Anemia, leg numbness and chronic pelvic pain have dissipated, and the patient has not experienced estrogen deficiency symptoms for more than two years.

Hum Reprod. 2009 Aug 17. [Epub ahead of print]

Combating endometriosis by blocking proteasome and nuclear factor-{kappa}B pathways.

Cvek B.

Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic.

Mol Hum Reprod. 2009 Oct;15(10):653-63. Epub 2009 Aug 14.

Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro.

Zhang H, Li M, Zheng X, Sun Y, Wen Z, Zhao X.

Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, People’s Republic of China.

In normal endometrium, stromal factors regulate the growth of epithelial cells. However, epithelial cells in endometriotic lesions display increased proliferation and decreased apoptosis. This work tested the hypothesis that in endometriosis stromal cells lose the ability to regulate survival signaling and cell growth in epithelial cells. Primary normal, endometriotic eutopic and ectopic epithelial cells were cultured in the presence of medium conditioned by normal, eutopic and ectopic endometriotic endometrial stromal cells. Endometriotic epithelial cells showed higher Survivin expression than normal epithelial cells. Conditioned medium (CM) from normal or eutopic endometriotic stromal cells significantly inhibited the Survivin expression and AKt phosphorylation in normal or eutopic endometriotic epithelial cells. However, CM from ectopic endometriotic stromal cells did not have an inhibitory effect on normal or ectopic endometriotic epithelial cells. Inhibition of AKt phosphorylation and Survivin expression in normal or eutopic endometriotic epithelial cells in the presence of stromal factors from normal or eutopic endometriotic stromal cells was enhanced by progesterone, whereas progesterone had little effect in the presence of stromal factors from ectopic endometriotic stromal cells. The inability of ectopic endometriotic stromal cells to regulated PI3K/AKt/Survivin signaling and mediate the progesterone response in endometriotic epithelial cells may facilitate epithelial cell proliferation in endometriosis and promote the survival of endometriotic lesions.

Hum Reprod. 2009 Aug 14. [Epub ahead of print]

The epidemiology of infertility in the North East of Scotland.

Bhattacharya S, Porter M, Amalraj E, Templeton A, Hamilton M, Lee AJ, Kurinczuk JJ.

Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Aberdeen AB25 2ZD, UK.

BACKGROUND There is a perception that the prevalence of infertility is on the rise. This study aimed to determine the current prevalence of infertility in a defined geographical population, ascertain changes in self-reported infertility over time and identify risk factors associated with infertility. METHODS A postal questionnaire survey of a random population-based sample of women aged 31-50 years was performed in the Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each time, whether medical advice had been sought and self-reported exposure to factors associated with infertility. RESULTS Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066 women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398 (9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9] had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respectively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chlamydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a similar survey of women aged 46-50 from the same geographical area, the prevalence of both primary infertility (>24 months) [70/1081, (6.5%) versus 68/710 (9.6%) P = 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P = 0.002] were significantly lower. CONCLUSIONS Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility in this population over the past 20 years.

Fertil Steril. 2009 Aug 13. [Epub ahead of print]

PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients.

McKinnon B, Bersinger NA, Huber AW, Kuhn A, Mueller MD.

Department of Obstetrics and Gynecology, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland.

Endometriosis is a significant gynecologic condition that can cause both pain and infertility and affects up to 15% of women during their reproductive years. In peritoneal endometriotic lesions, the expression of peroxisome proliferation-activated receptor gamma, a nuclear receptor with antiinflammatory and neuroprotective roles, is positively correlated with the pain reported by patients.

Zhongguo Zhong Yao Za Zhi. 2009 May;34(10):1285-9.

Inhibitory effect of Sanlengwan on expression of adhesion molecules ICAM-1, CD44 in rats of endometriosis

[Article in Chinese]

Li Z, Li A, Chen G, He Y, Wang J, Xu X.

Pharmaceutical Sciences College of Chongqing University of Medical Science, Chongqing 400016, China. cissylzh1983@yahoo.com.cn

OBJECTIVE: To explore the effect of Sanlengwan (SLW) on adhesion molecules expression and the accretion in ectopic endometrium of rats. METHOD: Endometriosis was established by surgical implant of endometrial tissue which belong to its body. Forty EMS model rats were randomly divided into five groups: model control group, three dose of SLW groups and anastrozole group. Meanwhile, eight normal rats were used as the normal group. All the rats were treated for 4 weeks respectively, and the volume of grafts were measured by vernier caliper, morphological changes were measured by HE stain, and the adhesion molecules, ICAM-1 and CD44 protein, were also measured by immunohistochemical test before and after treatment of SLW. RESULT: SLW markedly reduced the volume of grafts, improve the morphological characters and decreased the expression of ICAM-1 and CD44 in ectopic endometrial tissue. CONCLUSION: SLW can inhibit the accretion of ectopic endometrium tissue of rats, and its mechanism might be associated with inhibiting the expression of ICAM-1 and CD44 protein.

Gynecol Endocrinol. 2009 Aug 11:1-7. [Epub ahead of print]

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.

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.

Mol Hum Reprod. 2009 Oct;15(10):633-43. Epub 2009 Aug 11.

Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model.

Mönckedieck V, Sannecke C, Husen B, Kumbartski M, Kimmig R, Tötsch M, Winterhager E,

Grümmer R.

Institute of Molecular Biology, University Hospital Essen, 45122 Essen, Germany.

Progestins are successfully used in the treatment of endometriosis; however, the exact mechanisms of their action are still unsolved. We here focused on the effect of different progestins on parameters of extracellular matrix degradation and angiogenesis involved in the establishment and maintenance of ectopic endometrial lesions. Human endometrium was intraperitoneally transplanted into nude mice. After 7 and 28 days of treatment with progesterone, dydrogesterone, or its metabolite dihydrodydrogesterone, respectively, ectopic lesions were evaluated for proliferation and apoptosis. Expression of estrogen receptor alpha, progesterone receptor-AB, the angiogenetic factors, cysteine-rich angiogenic inducer (CYR61), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFA) and the matrix metalloproteinase (MMP)-2, -3, -7 and -9 was investigated. Functional impact on angiogenesis was evaluated by density of microvessels and of vessels stabilized by pericytes within the ectopic lesions. Although dydrogesterone significantly reduced proliferation of endometrial stromal cells after 28 days, suppression of apoptosis was independent from progestins. Expression of MMP-2 was significantly reduced by all progestins and MMP-3 by dydrogesterone. In the grafted endometrial tissue, transcription of bFGF was suppressed by progesterone and dihydrodydrogesterone, and VEGFA and CYR61 by dihydrodydrogesterone and dydrogesterone. In parallel, microvessel density was slightly suppressed by progestins, whereas number of stabilized vessels increased. Thus, progestins regulate factors important for the establishment and maintenance of ectopic endometrial lesions.

J Proteome Res. 2009 Oct;8(10):4622-32.

Comprehensive proteomic analysis of human endometrial fluid aspirate.

Casado-Vela J, Rodriguez-Suarez E, Iloro I, Ametzazurra A, Alkorta N, García-Velasco JA, Matorras R, Prieto B, González S, Nagore D, Simón L, Elortza F.

Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed, Technology Park of Bizkaia, Derio, Spain, Proteomika S.L. Technology Park of Bizkaia, Derio, Spain, Instituto Valenciano de Infertilidad, Madrid, Spain, Hospital de Cruces, Barakaldo, Spain, and Instituto Valenciano de Infertilidad, Bilbao, Spain.

The endometrial fluid is a noninvasive sample which contains numerous secreted proteins representative of endometrial function and reflects the state of the endometrium. In this study, we describe, for the first time, a comprehensive catalogue of proteins of the endometrial fluid during the secretory phase of the menstrual cycle. To achieve this objective, three different but complementary strategies were used: First, in-solution digestion followed by reverse phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS); second, protein separation by denaturing one-dimensional electrophoresis (SDS-PAGE) followed by HPLC-MS/MS analysis. Finally, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) followed by MALDI-TOF/TOF analysis. The combination of the three strategies led to the successful identification of 803 different proteins in the International Protein Index (IPI) human database (v3.48). An extensive description of the endometrial fluid proteome will help provide the basis for a better understanding of a number of diseases and processes, including endometriosis, endometrial cancer and embryo implantation. We believe that the thorough catalogue of proteins presented here can serve as a valuable reference for the study of embryo implantation and for future biomarker discovery involved in pathologic alterations of endometrial function.

Klin Khir. 2009 Mar;(3):39-41.

Catamenial pneumothorax: a rare manifestation of endometriosis

[Article in Ukrainian] [No authors listed]

Catamenial pneumothorax is an rare disease which arise in women during menses, etiologically related to endometriosis of diaphragm and lung. The five observations and literature review are presented. During 2006-2008 years 45 women with spontaneous pneumothorax were treated at Kyiv Clinical Hospital Number 17. Among them, catamenial pneumothorax was recognized in 5. In 3 women, diagnosis was established based on clinical data and thoracoscopy results, in 2–the cause of recurrent pneumothorax was seen intraoperatively. All the patients were operated on, in 2–videothoracoscopic diaphragm plication was done, in 2–we performed video-assisted resection of the affected part of the diaphragm, in 1–partial resection of the diaphragm was done with lateral thoracotomy. Abrasion of parietal pleura was performed in all patients. Endometrioid implants in the resected parts of diaphragm were confirmed histologically. No recurrences were observed during the average 32 months. The treatment of catamenial pneumothorax is symptomatic, to prevent recurrences and avoid illness every month. Since catamenial pneumothorax is caused by thoracic endometriosis, decisions on treatment should be made with a gynecologist’s opinion.

Gynecol Endocrinol. 2009 Aug 6:1-8. [Epub ahead of print]

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

Renner SP, Ekici AB, Maihofner 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.

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.

Steroids. 2009 Aug 7. [Epub ahead of print]

Estrogen-induced stromal cell-derived factor-1 (SDF-1/Cxcl12) expression is repressed by progesterone and by Selective Estrogen Receptor Modulators via estrogen receptor alpha in rat uterine cells and tissues.

Glace L, Grygielko ET, Boyle R, Wang Q, Laping NJ, Sulpizio AC, Bray JD.

Department of Urogenital Biology, Cardiovascular and Urogenital Center for Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA.

Endometriosis, defined as the presence of endometrial glands and stroma at extra-uterine sites, is a gynecological condition that affects women of reproductive age. Consistent with its uterine origins, endometriotic lesions and resulting symptoms are hormonally responsive. To investigate Progesterone Receptor (PR)-based therapies, we measured physiological endpoints and gene expression in rat models of uterine cell estrogenic activity. Estrogen-induced ELT-3 rat leiomyoma cell proliferation was significantly inhibited by progesterone (P4), while the antiprogestin RU486 or the Selective PR Modulator (SPRM) asoprisnil, did not block proliferation. Stromal cell-derived factor-1 (SDF-1/Cxcl12) gene expression was induced by estrogen, and was repressed by the Selective Estrogen Receptor Modulators (SERMs), the antiestrogen ICI 182,780, and P4, but not by RU486 or the ERbeta-selective ligand ERB-041. In ELT-3 cells, asoprisnil demonstrated partial PR agonism on SDF-1 gene repression. Magnetic Resonance Imaging was used to monitor development of ectopic cysts in a rat surgical model of endometriosis. SERMs and P4 significantly decreased cyst volumes comparably by approximately 60%. However, ERB-041 and asoprisnil had no effect on cyst volume, and RU486 increased cyst volume by 20%. SDF-1 expression was modestly, but significantly, increased in the cyst compared to eutopic uterus, and P4 and raloxifene could repress the expression. We showed that SDF-1 was similarly regulated in human cells. These data suggest that transcriptional regulation of SDF-1 is a surrogate marker of estrogenic activities via ERalpha in rat uterine cells, and that SDF-1 repression by PR agonists can predict the ability to oppose the actions of estrogen in vivo.

Eur J Obstet Gynecol Reprod Biol. 2009 Aug 6. [Epub ahead of print]

Recurrence rate of endometrioma after laparoscopic cystectomy: A comparative randomized trial between post-operative hormonal suppression treatment or dietary therapy vs. placebo.

Sesti F, Capozzolo T, Pietropolli A, Marziali M, Bollea MR, Piccione E.

Endometriosis Center, Section of Gynecology & Obstetrics, Department of Surgery, School of Medicine, Tor Vergata University Hospital, Viale Oxford, 81-00133 Rome, Italy.

OBJECTIVE(S): To assess the recurrence rate of endometrioma after laparoscopic cystectomy plus hormonal suppression treatment or plus dietary therapy compared to post-operative placebo. STUDY DESIGN: A randomized comparative trial was conducted on 259 consecutive women who underwent laparoscopic unilateral/bilateral cystectomy for endometrioma. Seven days after surgery, the patients were randomly allocated on the basis of a computer-generated randomization sequence, to one of four post-operative management arms as follows: placebo (n=65) or gonadotrophin-releasing hormone analogue (tryptorelin or leuprorelin, 3.75mg every 28 days) (n=65) or continuous low-dose monophasic oral contraceptives (ethynilestradiol, 0.03mg plus gestoden, 0.75mg) (n=64) or dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n=65) for 6 months. At 18 months’ follow-up after surgery, all patients were monitored with a clinical gynecologic examination, and a transvaginal ultrasonography for possible evidence of endometrioma recurrence. RESULT(S): At 18 months’ transvaginal ultrasonographic follow-up after surgery, no significant recurrence rate of endometrioma was detected in women who received a postoperative course of hormonal suppression treatment or dietary therapy when compared with placebo (placebo vs. GnRH-a P=0.316, placebo vs. estroprogestin P=0.803, placebo vs. dietary therapy P=0.544). Second-look laparoscopy was performed on a clinical basis and confirmed the ultrasonographic suspicion of recurrence of endometrioma in all cases: 10 (16.6%) in the post-operative placebo group vs. 6 (10.3%) in the post-operative GnRH-a group vs. 9 (15.0%) in the post-operative continuous estroprogestin group vs. 11 (17.8%) in the post-operative dietary therapy group. Of 36 patients with recurrent ovarian endometriosis, 8 had recurrence on the treated ovary, 20 on the contralateral ovary that appeared to be normal at the time of the first-line surgery, and 8 on both the treated and untreated ovaries. Endometrioma recurrences were associated with moderate-to-severe painful symptoms in 14/36 patients (38.8%), while the remaining 22 (61.1%) patients were asymptomatic. CONCLUSION(S): A 6-month course of hormonal suppression treatment or dietary therapy after laparoscopic cystectomy had no significant effect on the recurrence rate of ovarian endometriosis when compared with surgery plus placebo. So, treatment of endometrioma can be carried out exclusively by laparoscopic cystectomy without post-operative therapy, if a complete excision of ovarian endometriosis has been assured.

OMICS. 2009 Oct;13(5):381-96.

Resampling reveals sample-level differential expression in clinical genome-wide studies.

Hiissa J, Elo LL, Huhtinen K, Perheentupa A, Poutanen M, Aittokallio T.

Biomathematics Research Group, Department of Mathematics, University of Turku, Turku, Finland.

Genome-scale molecular profiling of clinical sample material often results in heterogeneous datasets beyond the capability of standard statistical procedures. Statistical tests for differential expression, in particular, rely upon the assumption that the sample groups being compared are relatively homogeneous. Such assumption rarely holds in clinical materials, which leads to detection of secondary findings (false positives) or loss of significant targets (false negatives). Here, we introduce a resampling-based procedure, named ReScore, which aggregates individual changes across all the samples while preserving their clinical classes, and thereby provides multiple sets of markers that can effectively characterize distinct sample subsets. When applied to a public leukemia microarray study, the procedure could accurately reveal hidden subgroup structures associated with underlying genotypic abnormalities. The procedure improved both the sensitivity and specificity of the findings, as well as helped us to identify several disease subtype-specific genes that have remained undetected in the conventional analyses. In our endometriosis study, we were able to accurately distinguish between various sources of systematic variation, linked, for example, to tissue-specificity and disease-related factors, many of which would have been missed with standard approaches. The generic procedure should benefit also other global profiling experiments such as those based on mass spectrometry-based proteomic assays.

Clin Obstet Gynecol. 2009 Sep;52(3):380-9.

Pediatric and adolescent gynecologic laparoscopy.

Broach AN, Mansuria SM, Sanfilippo JS.

Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA.

Minimally invasive techniques to treat children and adolescents requiring surgery have increasingly become standard of care. Similarly, gynecologists frequently use laparoscopy to treat pelvic pathology. We present the necessary equipment and surgical techniques required to perform gynecologic procedures on the pediatric and adolescent population. We will give particular focus to the treatment of adnexal masses, chronic pelvic pain, endometriosis, and ovarian torsion. We will also discuss the role of the incidental appendectomy in children and adolescents.

Clin Obstet Gynecol. 2009 Sep;52(3):351-61.

Laparoscopic surgery for endometriosis.

Catenacci M, Sastry S, Falcone T.

The Cleveland Clinic, Department of Obstetrics and Gynecology, 9500 Euclid Avenue, Cleveland, OH, USA.

Endometriosis is a leading cause of pelvic pain and infertility in women. Laparoscopy can both diagnose and treat this disease. The aim of this review was to examine current literature on treatments for endometriosis for both pain and infertility. Evidence supports removal of severe disease, including ovarian endometriomas, for improved pregnancy outcomes. However, for patients that fail initial surgery, in vitro fertilization may yield superior outcomes over repeat surgery. For pelvic pain, surgery has been shown to improve symptoms although there is a significant placebo effect with surgery. Finally, hysterectomy can be offered to women who fail initial conservative surgery.

Clin Obstet Gynecol. 2009 Sep;52(3):344-50.
Tubal surgery.

Zarei A, Al-Ghafri W, Tulandi T.

Department of Obstetrics and Gynecology, McGill University, Pine Avenue West, Montreal, QC, Canada.

Today, reproductive surgery has a limited place. In selected cases such as young women with a history of pelvic inflammatory disease, pelvic adhesions, and endometriosis, surgery could be considered. Most operations can be performed by laparoscopy; these include tubal anastomosis that yields a high pregnancy rate. On the other hand, women over the age of 37 with a long history of infertility or those who require a laparotomy are better treated with in-vitro fertilization. For women with hydrosalpinx undergoing IVF, salpingectomy is the best treatment option. It increases the chance of pregnancy and live birth rates and decreases the miscarriage rate.

Reproduction. 2009 Aug 6. [Epub ahead of print]

Association between MMP1 and MMP9 activities and ICAM1 cleavage induced by TNF in stromal cell cultures from eutopic endometria of women with endometriosis.

Pino M, Galleguillos C, Torres M, Sovino H, Fuentes A, Boric MA, Johnson MC.

M Pino, Institute of Maternal and Child Research, University of Chile, Santiago, Chile.

Endometriosis is a benign gynecological pathology in which immune system deregulation may play a role in its initiation and progression. In endometriotic lesions, ICAM1 is released from the cell membrane by proteolytic cleavage of its extracellular domain, a process that coincides with increased expression and proteolytic activity of metalloproteinases such as MMP1 and MMP9. The objective of our study was to investigate the association between MMP1 and MMP9 activities and ICAM1 cleavage mediated by TNF in eutopic endometrial stromal cells from women with and without (control) endometriosis during culture. The RNA was evaluated by RT-PCR, and the protein was determined by western blot (ICAM1, MMP1), casein or gelatin zymographies (secreted active MMP1 or MMP9, respectively), ELISA (sICAM1), and fluorescence assay (secreted active MMP1). Under basal conditions, proMMP9 dimer and MMP9 were higher in endometriosis cell cultures. In stromal cultures derived from control women and those with endometriosis, TNF augmented the intracellular proMMP1 (1.2-fold in control stromal cells) and ICAM1 (1.4- and 1.9-fold), greatly increased MMP1 and proMMP9 levels, and the sICAM1 concentration (2.3- and 4.3-fold) in their media compared to basal levels. The combination of TNF and MMP9 increased the sICAM1 concentration by 14-fold in the endometriosis cell media, whereas GM6001 inhibited the stimulatory effect of TNF in both cell cultures. The deregulation of MMP9, and the TNF participation in the MMP1 and proMMP9 secretions, in the MMP9 expression and in the expression and cleavage of ICAM1 may contribute to the pathophysiology of this disease.

Hum Reprod. 2009 Aug 6. [Epub ahead of print]

Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium.

Gomes MK, Rosa-E-Silva JC, Garcia SB, de Sá Rosa-E-Silva AC, Turatti A, Vieira CS, Ferriani RA.

Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.

BACKGROUND The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. METHODS Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor alpha (ER-alpha) were analyzed by immunohistochemistry. RESULTS The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER-alpha and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers. CONCLUSIONS LNG-IUS reduced both cell proliferation and the expression of PRA and ER-alpha and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.

Mol Hum Reprod. 2009 Oct;15(10):645-52. Epub 2009 Aug 6.
Connexin expression pattern in the endometrium of baboons is influenced by hormonal changes and the presence of endometriotic lesions.

Winterhager E, Grümmer R, Mavrogianis PA, Jones CJ, Hastings JM, Fazleabas AT.

Institute of Molecular Biology, University of Duisburg-Essen, 45122 Essen, Germany. elke.winterhager@uk-essen.de

Experimentally induced endometriosis in baboons serves as an elegant model to discriminate between endometrial genes which are primarily associated with normal endometrial function and those that are changed by the presence of endometriotic lesions. Since connexin genes are characteristic of the hormonally regulated differentiation of the endometrium, we have examined connexin expression in baboon endometrium to delineate if they are altered in response to the presence of endometriotic lesions. Connexin expression in the endometrium of cycling baboons is similar to that of the human endometrium with Connexin(Cx)43 being primarily seen in the stromal compartment and Cx26 and Cx32 being present predominantly in the epithelium. Although Cx32 is up-regulated during the secretory phase, Cx26 and Cx43 are down-regulated. In the baboon model of induced endometriosis a change in connexin pattern was evident in the presence of endometriotic lesions. In the secretory phase, Cx26 and Cx32 are no longer present in the epithelium but Cx26 is now observed primarily in the stromal cells. Infusion of chorionic gonadotrophin in a manner that mimics blastocyst transit in utero failed to rescue the aberrant stromal expression of Cx26 that is associated with the presence of endometriotic lesions suggesting an impairment of the implantation process. The altered connexin pattern coupled with a loss of the channel protein in the epithelium and a gain of Cx26 in the stromal compartment suggests that the presence of lesions changes the uterine environment and thereby the differentiation programme. This aberrant expression of connexins may be an additional factor that contributes to endometriosis-associated infertility. 

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