Fertil Steril. 2010 Apr 16. [Epub ahead of print]Rare case of perplexing ovarian endometriosis.van der Merwe JL, Siebert I, van Wyk AC.Department of Obstetrics and Gynaecology, Tygerberg Hospital and Stellenbosch University, Tygerberg, South Africa.OBJECTIVE: To document a rare case of coexisting endometriosis and mature cystic teratoma in the same ovary. ...
Mol Hum Reprod. 2009 Oct;15(10):693-701. Epub 2009 Jun 5.
Dienogest, a synthetic progestin, inhibits the proliferation of immortalized human endometrial epithelial cells with suppression of cyclin D1 gene expression.
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba 412-8524, Japan. email@example.com
Dienogest is a specific progesterone receptor agonist with potent oral endometrial activity and is used in the treatment of endometriosis. In this study, we examined the direct effects of dienogest on the proliferation of human endometrial epithelial cells using an immortalized cell line. 5-Bromo-2′-deoxyuridine incorporation into the cells was inhibited by dienogest and by progesterone (P(4)) in dose-dependent fashion at concentrations of 10(-8) mol/l or higher. To identify the target genes of dienogest and P(4), we screened the expression of 84 genes related to cell cycle regulation by real-time polymerase chain reaction after 6 h of treatment at a concentration of 10(-7) mol/l. Results showed that only cyclin D1 expression was significantly down-regulated, although expression of the other genes did not significantly change after dienogest or P(4) treatment compared with the control. In a time-course study during the first 24 h after drug treatment, dienogest and P(4) each produced a lasting decrease in the expression of cyclin D1 mRNA, followed by a decrease in cyclin E1 mRNA but not an increase in the expression of cell cycle inhibitor genes (p21, p27 and p53). These findings suggest that dienogest directly inhibits the proliferation of human endometrial epithelial cells with suppression of cyclin D1 gene expression.
Kaohsiung J Med Sci. 2009 Apr;25(4):217-21.
Endoscopic management of a ureteral obstruction caused by endometriosis: a case report.
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 49-year-old female (gravida 3, para 2, abortion 1), who was identified as suffering from right hydronephrosis while undergoing her regular health examination. Retrograde pyelography demonstrated a partial obstruction of the right ureter in the distal third. She underwent ureteroscopy and biopsy to remove a right ureteral tumor. Histological examination confirmed ureteral endometriosis. During follow-up at the obstetrics and gynecology outpatient department, an abdominal echo was detected that revealed a right endometrioma (size, 7.5 x 4.8 x 5.5 cm) on the ovary. As a result, a total hysterectomy and bilateral salpingo-oophorectomy was performed. Although the patient had right residual hydronephrosis, the creatinine level improved to 1.2 mg/dL during follow-up.
Fertil Steril. 2009 Oct;92(4):1240-2. Epub 2009 Jun 6.
Association between patient age at the time of surgical treatment for endometriosis and aryl hydrocarbon receptor repressor polymorphism.
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
A cross-sectional comparative study among women who underwent surgical treatment for endometriosis revealed that frequency of the Ala/Ala genotype at aryl hydrocarbon receptor repressor (AHRR) Pro185Ala polymorphism was three times higher (27.6% vs. 9.9%) in the younger group (<or=30 years) than in the older group (>30 years). AHHR genotyping may help to identify a subpopulation of women who are susceptible to the earlier onset of endometriosis.
Fertil Steril. 2009 Oct;92(4):1246-9. Epub 2009 Jun 6.
Endometrium from women with endometriosis shows increased proliferation activity.
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea.
Examination of 631 infertile women, including 434 women with endometriosis and 197 without endometriosis, revealed an increasing incidence of endometrial polyps, especially in the test subjects with endometriosis, and advanced stages of endometriosis. Expression of Ki-67 and Bcl-2 proteins and MTT assay results were significantly higher in endometrium of patients with endometriosis than in patients without endometriosis. These showed increased proliferation activity and cell proliferation markers not only clinically but also pathologically.
Gynecol Endocrinol. 2009 Jun 2:1-3. [Epub ahead of print]
Dienogest and the breast.
Institute for Medical Research and Education, Essen, Germany.
In a clinical pilot study, 21 women with endometriosis have been primarely treated with dienogest 2 x 10 mg daily p.o. for 24 weeks. Besides the effect on endometriosis the action of such high-dose progestogen treatment on the breast was evaluated by breast ultrasound prior to medication and at 24 weeks of medical treatment. In all women, a significant size reduction of the mammary gland (p < 0.023) and regression of mastopathic changes were observed. There was a non-significant reduction (p = 0.089) of the maximum diameter of the ducts. The portion of the fatty tissue increased slightly, but not significantly (p = 0.348).
Gynecol Endocrinol. 2009 Jun 2:1-6. [Epub ahead of print]
Role of CYP2C19 polymorphisms in patients with endometriosis.
Department of Obstetrics and Gynecology.
Aim. To investigate the association of CYP2C19 genotypes with endometriosis. Methods. The study included 100 women who underwent laparotomy or laparoscopy: 50 patients with endometriosis diagnosed with surgery and histopathology, and 50 control subjects who had no evidence of endometriosis during exploratory laparotomy or laparoscopy. Genomic DNA of subjects was extracted from the whole blood using High Pure PCR template preparation kit. Genotyping of CYP2C19 polymorphisms were detected by using a LightCycler CYP2C19 mutation detection kit in a real-time PCR, and were compared between the two groups. Results. Logistic regression analyses showed that the CYP2C19*2 heterozygote genotype was associated with a significantly increased risk of endometriosis. The odds ratio of endometriosis for the CYP2C19*2 heterozygote genotype was 3.165 (p = 0.023) compared with the control group. CYP2C19*3 genotype was detected as wild in all subjects in the endometriosis and control groups. Conclusion. Our results suggest that CYP2C19*2 heterozygote genotype has higher risk of developing endometriosis. Therefore, CYP2C19*2 allele gene polymorphisms may be associated with genetic susceptibility of endometriosis.
Gynecol Endocrinol. 2009 Jun 2:1-6. [Epub ahead of print]
Clinical manifestations in patients with ovarian clear cell carcinoma with or without co-existing endometriosis.
Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Korea, Goyang, Gyeonggi, Republic of Korea.
Objectives. The symptoms associated with ovarian cancer are vague. Endometriosis, which causes dysmenorrhea and dyspareunia, is frequently detected along with ovarian clear cell carcinoma (OCCC). We have therefore evaluated the clinical manifestations of OCCC based on the co-existence of endometriosis. Methods. A retrospective analysis was conducted on 43 patients who had been treated for OCCC at the National Cancer Center between June 2000 and July 2007. Using medical records and the cancer registry, the clinical features and laboratory findings were analysed. Results. Endometriosis was identified in 16 (37.2%) of the 43 patients with OCCC. The main presenting symptoms included a hard, palpable mass (32.6%), and newly developed or an exacerbation of dysmenorrhea (32.6%) and dyspareunia (25.6%). Gastrointestinal symptoms, pelvic pain, and abdominal distension existed in nine (20.9%), eight (18.6%) and one (2.3%) of the patients, respectively. The symptoms did not differ statistically in patients with or without endometriosis. Thirty-seven percent (11/30) of the patients had a normal CA-125 level (<35 U/ml); 18.8% (3/16) of the patients without endometriosis and 57% (8/14) of the patients with endometriosis had normal levels of CA-125 (<35 U/ml). Nine of 16 (56.3%) patients with early stage OCCC had a normal CA-125 level. Conclusions. The main presenting symptoms in patients with OCCC include a hard, palpable mass, dysmenorrhea and dyspareunia, irrespective of co-existing endometriosis. A normal CA-125 level has limited value in excluding OCCC, especially in the early stages.
Am J Pathol. 2009 Jul;175(1):225-34. Epub 2009 Jun 4.
Reactive oxygen species controls endometriosis progression.
Faculté de Médecine, Service de Gynécologie Obstétrique II et Médecine de la Reproduction, AP-HP Hôpital Cochin, Paris, France.
Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.
Am J Pathol. 2009 Jul;175(1):215-24. Epub 2009 Jun 4.
Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS.
Pelvic Pain and Endometriosis Unit, Gynecology Department, Molecular Gynecology and Proteomics Laboratory, Universidade Federal de São Paulo – Escola Paulista de Medicina, São Paulo, Brasil. firstname.lastname@example.org
Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.
Drugs. 2009;69(8):943-52. doi: 10.2165/00003495-200969080-00001.
Pharmacological treatment of endometriosis: experience with aromatase inhibitors.
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, Genoa, Italy. email@example.com
Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. In the last 10 years, it has been demonstrated that aromatase P450, a key enzyme for estrogen biosynthesis, may have a pathogenic role in endometriosis because it is aberrantly expressed in endometriotic implants and in eutopic endometrium of women with endometriosis. Therefore, inhibition of aromatase activity may represent a new therapeutic option for endometriosis. Case reports and observational studies have shown that pain symptoms caused by endometriosis quickly improve after administration of aromatase inhibitors. Limited data are available on the long-term course of pain symptoms after completion of treatment with aromatase inhibitors; however, some recent studies suggest that symptoms may recur at short-term follow-up. A range of results are reported on the effects of aromatase inhibitors on endometriotic lesions, with some authors describing improvements and other authors reporting persistence of pelvic lesions at second-look laparoscopy after treatment. No severe adverse effect has been reported during treatment with aromatase inhibitors both in pre- and postmenopausal women. On the basis of the available data, administration of aromatase inhibitors should now be offered only to the small number of women who have severe pain despite previous surgical and hormonal therapies. Further research in the form of randomized controlled trials will be required before recommending the routine use of these agents.
Ginecol Obstet Mex. 2009 Apr;77(4):183-8.
Syndrome premenstrual dysphoric 185 preschool teachers in Mérida Yucatán
[Article in Spanish]
Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, México.
BACKGROUND: Premenstrual dysphoric syndrome affects 3 to 8% of women. It is a disabling health problem, family and socio-economic impact. This syndrome increases the risk of: major depressive disorder, postpartum depression and other serotonin spectrum pictures. In Yucatan, there are no specific reports on the frequency of dysphoric premenstrual syndrome. OBJECTIVE: To determine the prevalence and the most common symptoms of premenstrual dysphoric syndrome in a group of preschool teachers in Merida, Yucatan. MATERIALS AND METHODS: a descriptive study conducted from October 2006 to January 2007 with a probability sample of 77 teachers. A questionnaire was applied and provided a table with data related to premenstrual dysphoric syndrome, which was completed daily during two menstrual cycles. Data was analyzed with descriptive statistics in Epi Info V6. RESULTS: Forty-six women (59.7%) had regular menstrual cycles and 30 (39%) suffered from a previously diagnosed disease (premenstrual syndrome, endometriosis, acute anemia, migraine, hypothyroidism). Of the 77 women, 27.3% (21/77) had positive result for premenstrual dysphoric syndrome. The most frequent symptoms were physical, that require that patients seek the help of a professional or self-medication, this did not happen when the symptoms were kind of emotional or behavioral disability occurred although, even for everyday activities. CONCLUSIONS: The percentage of patients with premenstrual dysphoric syndrome was higher than that reported in the literature. The daily monitoring of symptoms caused by the menstrual cycle and enables doctors to identify women premenstrual dysphoric syndrome and avoid its consequences.
Methods Mol Biol. 2009;550:137-57.
Current methods in investigating the development of the female reproductive system.
Institut National de la Recherche Scientifique (INRS) – Institut Armand Frappier, Université du Québec, Quéebec, Laval, Canada.
The female reproductive system is important as the site for development and fertilization of an oocyte, for implantation and development of an embryo, and for growth and delivery of the fetus. It also produces protein and steroid hormones that help maintain a female’s health. Although the female phenotype is the default pathway for the development of the urogenital system, many processes can become disrupted during and after development which may originate from developmental problems. Improper development can be the underlying cause of structural malformations, sub- or infertility, hormonal abnormalities, endometriosis, carcinogenesis, or other detrimental outcomes. Our research programs examine the normal physiology and function of the female reproductive system and how it can become damaged due to pathologies or environmental/therapeutic exposures, with a focus on the ovary, ovarian follicles, and ovarian hormones. This chapter will describe detailed protocols of an in vitro organ culture system and methods to analyze changes in follicle formation, follicle development, and ovarian physiology. These methods can also be applied to the study of other aspects of female reproduction.
Hum Reprod. 2009 Sep;24(9):2133-41. Epub 2009 Jun 2.
Absence of aromatase protein and mRNA expression in endometriosis.
Université Catholique de Louvain, Faculty of Medicine, Gynecology Unit, 1200 Brussels, Belgium.
BACKGROUND: Aromatase has been reported to be involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of endometriosis patients. The objective of the present study was to investigate its expression and localization in three distinct types of endometriosis. METHODS: Human peritoneal, ovarian and rectovaginal endometriotic lesions and matched eutopic endometrium were collected from patients during laparoscopy. Aromatase protein localization (immunohistochemistry, n = 63) and mRNA expression [quantitative polymerase chain reaction (Q-PCR), n = 64] were assessed. RESULTS: No aromatase protein was detected by immunohistochemistry in either the glandular or stromal compartment of endometriotic lesions or eutopic endometrium, while it was strong in placental syncytiotrophoblasts, granulosa and internal theca cells from pre-ovulatory follicles, and luteal cells from corpus luteum. By Q-PCR, low but discernible levels of aromatase expression were found in endometriomas, probably due to follicular expression. Transcripts for aromatase were barely detectable in only a few peritoneal and rectovaginal endometriotic lesions, and a few eutopic endometrium samples, probably due to contaminating surrounding tissues (adipose tissue, intact peritoneum). CONCLUSIONS: Unlike previous studies, we observed no aromatase protein in any of the endometriosis types, and barely detectable aromatase mRNA expression, suggesting that locally produced aromatase (within endometriotic lesions) may be less implicated in endometriosis development than previously postulated. Potential factors responsible for these discrepancies are discussed.
Eur J Obstet Gynecol Reprod Biol. 2009 Aug;145(2):180-3. Epub 2009 Jun 2.
The V109G polymorphism in the p27 gene is associated with endometriosis.
Federal University of São Paulo, Escola Paulista de Medicina, Gynecology Department, Sao Paulo, SP, Brazil.
OBJECTIVE: To investigate the prevalence of the p27 gene polymorphism in women with endometriosis. STUDY DESIGN: Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population. RESULTS: We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p=0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR=1.9; 95% CI, 1.120-3.343). CONCLUSION: The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.
Int J Gynecol Pathol. 2009 Jul;28(4):334-7.
Symplastic atypia in neoplastic and non-neoplastic endometrial stroma: report of 3 cases with a review of atypical symplastic cells within the female genital tract.
Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland.
SUMMARY: We report 3 cases in which endometrial stromal cells exhibited marked nuclear atypia with a symplastic appearance. Two cases involved non-neoplastic endometrial stroma, one within an ovarian endometriotic cyst and the other within normal eutopic endometrium. In the third case, the symplastic change involved the neoplastic cells of an endometrial stromal sarcoma. Symplastic endometrial stromal cells have rarely been described in normal endometrium and in endometrial stromal sarcoma but, as far as we are aware, this phenomenon has not been reported previously in endometriosis. In the 3 cases, the atypical cells were a focal finding. The abnormal nuclei were markedly enlarged, atypical, and hyperchromatic with multilobated forms but without mitotic activity. This unusual phenomenon is a benign change when involving non-neoplastic endometrial stroma and is of no clinical significance. It is analogous to the presence of atypical symplastic nuclei in normal tissues and in other pathologic lesions in the female genital tract. In reporting these cases, we review normal tissues and pathologic lesions in the female genital tract with atypical symplastic nuclei.
Int J Gynecol Pathol. 2009 Jul;28(4):362-6.
Coexistence of a clear cell adenocarcinoma and an adenosarcoma with a heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary: a case study.
Department of Clinical Laboratory Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan.
SUMMARY: A rare case of a clear cell adenocarcinoma and an adenosarcoma coexisting with a heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary is reported. The tumor was composed of a cystic area and a solid area arising from the cyst wall. In the cystic lesion, a detached polypoid mass was also identified. The cyst wall was lined with a single layer of endometrial-type cells, whereas the solid area was composed of a clear cell adenocarcinoma. In the detached polypoid mass, an exophytic leaf-like pattern containing benign endometrial-type cells and squamous epithelial and rhabdomyosarcoma components, which were positive for desmin and myoglobin, was observed. Using X-chromosomal clonality assay, these clear cell adenocarcinoma and adenosarcoma components showed patterns of polyclonality. To the authors’ knowledge, this is the first reported case of a clear cell adenocarcinoma and an adenosarcoma coexisting with heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary.
Mol Hum Reprod. 2009 Jul;15(7):411-9. Epub 2009 May 29.
Superoxide dismutase expression in human cumulus oophorus cells.
Laboratory of Cell and Molecular Biology, Faculty of Medicine, University of Porto, Porto, Portugal.
Success in assisted reproductive techniques (ART) is influenced by gamete and embryo quality but the assessment of these parameters has been thwarted by the lack of reliable biomarkers. Follicular fluid and cumulus oophorus cells may provide biomarkers due to their close relationship to the oocyte. These cells produce antioxidants and thus protect the oocyte from oxidative damage exerted by reactive oxygen species (ROS). ROS and antioxidants are known to intervene in reproductive physiology and pathology, but their roles are unclear. It is hypothesized that superoxide dismutase (SOD), a first line antioxidant enzyme, is associated with oocyte quality. Cells obtained in the course of ART for the treatment of infertility due to male factor or female pathology were processed for SOD intracellular isoforms (CuZnSOD and MnSOD) immunodetection, total SOD activity and isoforms content. Cells presented strong positive staining for CuZnSOD and MnSOD. SOD activity decreased with increasing female age but was increased in endometriosis and in ovulatory dysfunction. When male factor was the cause for infertility, successful ART was associated with higher SOD activity. Variations in SOD emphasize the relevance of oxidative stress in the oocyte maturation process. These variations also suggest that SOD is a potential biomarker for ART success.
Front Biosci (Elite Ed). 2009 Jun 1;1:455-65.
Treatment of endometriosis-related pain: options and outcomes.
Dept of Obstetrics and Gynecology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Endometriosis-associated pain represents a challenge for both the patient and the health care provider since it is often difficult to design treatment strategies resulting in improvement of the symptoms. The association between endometriosis stage and severity of pelvic symptoms is limited. Surgery is generally considered the first line treatment in women affected, at least in those who have not been previously operated, but there are several situations in which medical treatments are useful. Given their good tolerability, minor metabolic effects and low cost, progestogens with or without the addition of estrogens, can be considered the drugs of choice and are currently the only safe and inexpensive alternative to surgery. Progestogens are effective in controlling pain symptoms in approximately three of four women with endometriosis. There is little or no difference in the effectiveness of GnRH agonist and add-back treatment in comparison with other medical treatments for endometriosis while the surgical interruption of pelvic nerve pathways entail some clinically relevant risks.
Front Biosci (Elite Ed). 2009 Jun 1;1:444-54.
Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis.
Leuven University Fertility Centre, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium.
A clear picture of the dynamic relationship between the endometrium and peritoneum is emerging as both tissues may participate in the spontaneous development of endometriosis. Various adhesion molecules, pro-inflammatory cytokines and chemoattractants cytokines have emerged as central coordinators of endometrial-peritoneal interactions. The peritoneal microenvironment which consists of the peritoneal fluid, normal peritoneum and peritoneal endometriotic lesions may play an active role in the pathogenesis of endometriosis, by harbouring most inflammatory responses that are triggered by the presence of endometrial cells, leading to recruitment of activated macrophages and leukocytes locally. Menstrual endometrium has the ability to bond and invade the peritoneal tissue. In baboons intrapelvic injection of menstrual endometrium permits the study of early endometrial-peritoneal interaction in an in vivo culture microenvironment and can lead to important insight in the early development of endometriotic lesions. In this review, we discuss the roles of the endometrial-peritoneal interactions, not only in disease development but also in the broader process of aetiopathogenesis.
Front Biosci (Elite Ed). 2009 Jun 1;1:429-43.
Immune – endocrine interactions in endometriosis.
Yale University School of Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, New Haven, CT, 06510.
Endocrine and immune systems are among the most essential regulators of endometrial physiology, and immune-endocrine interactions are likely to be involved in the pathogenesis of endometriosis. Endometriosis is an inflammatory, estrogen-dependent disease defined by the presence of viable endometrial tissue outside the uterine cavity. Impaired immune response that results in inadequate removal of refluxed menstrual debris has been proposed as a possible causative factor in the development of endometriosis. Moreover, decrease in spontaneous apoptosis of endometrium is the other theory proposed for the development of endometriosis. Endometriotic tissues respond to sex steroids aberrantly and behave differently compared to endometrium in addition to their ability to produce local estrogen. The effects of estrogen on distinct intracellular signaling pathways including MAPK, PI3K/AKT and NF-kappa B may take a role in enhanced endometrial cell survival, altered immune response, and differential cytokine and chemokine expression in endometriosis. Better understanding of immune-endocrine interactions will set the stage for effective immune-targeted therapies not only for endometriosis but also for other endometrial diseases such as adenomyosis, recurrent reproductive failure and implantation-related infertility.
Front Biosci (Elite Ed). 2009 Jun 1;1:415-28.
Insights into endometriosis-associated endometrial dysfunctions: a review.
Unite d’Endocrinologie de la Reproduction, Centre de Recherche, Hopital Saint-Francois d’Assise, Centre Hospitalier Universitaire de Quebec (CHUQ), Faculte de Medecine, Universite Laval. 10, rue de l’Espinay, local D0-711, Quebec, G1L 3L5 Canada.
Endometriosis is defined as the presence of ectopic endometrial-like tissue outside the uterus cavity. This disease, afflicting women during their reproductive age, is mainly associated with pelvic pain and infertility. Sampson’s theory which supports the ability of endometrial fragments from retrograde menstruations to slough through fallopian tubes and reach peritoneal environment has been recognized as the most plausible explanation for endometriosis during many years. However, further studies provided evidence that fundamental abnormal changes may occur within the eutopic endometrium of women with endometriosis compared to that of women without endometriosis. These dysfunctions included genetic predisposition, genes aberrantly expressed such as matrix metalloproteinases, Hox genes, integrins, anti-apoptotic genes Bcl-2, but also steroid hormones, immuno-inflammatory factors and angiogenesis. This review aims at summarizing and emphasizing a non exhaustive panel of biochemical and molecular factors abnormally expressed in the eutopic endometrium and related to the pathogenesis of endometriosis.
Eur J Obstet Gynecol Reprod Biol. 2009 Sep;146(1):15-21. Epub 2009 May 30.
Repetitive surgery for recurrent symptomatic endometriosis: what to do?
Department of Obstetrics and Gynaecology, University of Milan, Istituto Luigi Mangiagalli, Via Commenda 12-20122 Milan, Italy. firstname.lastname@example.org
In spite of the increasing number of operative laparoscopies performed for endometriosis associated pelvic pain, postoperative symptomatic recurrences are very common. Reoperation is often considered the best treatment option, but the extent and duration of the effect of second-line surgery is still unclear. The best available evidence has been reviewed in order to define the results of repetitive conservative surgery, the effects of pelvic denervating procedures and postoperative medical treatments, as well as the long-term outcome of definitive surgery. Because of the paucity of published data, estimating the real risk of symptomatic recurrence and need for reoperation after repetitive conservative surgery for endometriosis is very difficult. Based on the limited information available, the long-term outcome appears suboptimal, with a cumulative probability of pain recurrence between 20% and 40%, and of a further surgical procedure between 15% and 20%. These figures are probably an underestimate related to drawbacks in study design, exclusions of dropouts, and publication bias and should be considered with caution. Systematic complementary performance of denervating procedures in addition to reoperation cannot be recommended, as only a few symptomatic patients complain of predominantly midline, hypo-gastric pain. The outcome of hysterectomy for endometriosis-associated pain at medium-term follow-up seems quite satisfactory. Nevertheless, about 15% of patients had persistent symptoms, and 3-5% experienced worsening of pain. Concomitant bilateral oophorectomy reduced the risk of reoperation due to recurrent pelvic pain by six times. However, at least one gonad should be preserved in young women, especially in those with objections to the use of oestrogen-progestogens. Medical treatment appears to have limited and inconsistent effects when used for only a few months after conservative procedures. Data on the benefit of prolonged drug regimens with oral contraceptives or progestogen are lacking. The risk of recurrence of endometriosis during hormone replacement therapy seems marginal if combined preparations or tibolone are used and oestrogen-only treatments are avoided. The opportune surgical solution in women with recurrent symptoms after previous conservative procedures for endometriosis should be based on the desire for conception as well as on psychological characteristics. Studies on surgical management of recurrent rectovaginal endometriosis are warranted, due to the peculiar technical difficulties as well as the high risk of complications associated with this challenging disease form.
Fertil Steril. 2009 May 29. [Epub ahead of print]
Conservative laparoscopic management of urinary tract endometriosis (UTE): surgical outcome and long-term follow-up.
Minimally Invasive Gynecologic Surgery Unit, University of Bologna.
OBJECTIVE: To evaluate surgical outcome and long-term follow-up of conservative laparoscopic management of urinary tract endometriosis (UTE). DESIGN: Prospective study. SETTING: Tertiary-care university hospital. PATIENT(S): Women with laparoscopic diagnosis and histologic confirmation of urinary bladder or ureteral endometriosis who agreed to undergo long-term follow-up after laparoscopic management. INTERVENTION(S): (1) Laparoscopic partial cystectomy for bladder endometriosis. (2) Uretric endometriosis laparoscopically managed by: uretrolysis only; segmental ureterectomy and terminoterminal anastomosis; or segmental ureterectomy and uretrocystoneostomy. MAIN OUTCOME MEASURE(S): Variables assessed were: preoperative findings, operative details (type and site of UTE, type of intervention, perioperative complications), and long-term follow-up (persistence/recurrence of preoperative urinary symptoms, if present, and anatomic relapse of the disease). RESULT(S): Mean operating time was 152.8 +/- 41.7 minutes. Mean drop in hemoglobin was 1.9 +/- 1.6 g/dL. Average hospital stay was 6 days. After surgery, 11 women had fever >38 degrees C and four presented transient urinary retention. During a follow-up period of 36 months, endometriosis recurred in eight patients with no evidence of bladder or ureteral reinvolvement, and there was a significant reduction in the mean score of dysuria and suprapubic pain maintained during the whole follow-up period. CONCLUSION(S): Results of long-term follow-up demonstrate significant reduction in preoperative symptoms with no anatomic relapse.
Gynecol Oncol. 2009 Aug;114(2):188-94. Epub 2009 May 29.
Laparoscopic optical coherence tomography imaging of human ovarian cancer.
Department of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721-0104, USA.
OBJECTIVES: Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. METHODS: A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. RESULTS: Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. CONCLUSIONS: We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.
Gynecol Obstet Invest. 2009;68(2):88-103. Epub 2009 May 27.
Surgery for deep endometriosis: a pathogenesis-oriented approach.
Department of Obstetrics and Gynecology, Istituto Luigi Mangiagalli, University of Milan, IT-20122 Milan, Italy. email@example.com
BACKGROUND: Deep endometriosis is usually associated with severe symptoms and constitutes a complex treatment challenge. METHODS: The available evidence has been revisited with the aim of defining an effective diagnostic workup and a safe surgical strategy based on pathogenetic findings. RESULTS: Vaginal, rectal, and bladder detrusor endometriosis appear to be caused by intraperitoneal seeding of regurgitated endometrial cells which implant in the posterior and anterior cul-de-sac and trigger an inflammatory process leading to adhesion of contiguous organs. Excision of posterior deep lesions implies removal of a fibrotic cast of the Douglas’s pouch which may involve the posterior vaginal fornix and the rectal muscular layer, with a not negligible risk of major complications. Removal of full-thickness bladder detrusor endometriosis entails excision of the bladder dome or posterior wall, generally well above the trigone. Transurethral resection is contraindicated. A radical approach to obstructive uropathy is suggested, with resection of the stenotic ureteral tract and reimplantation with antireflux vesicoureteral plasty. CONCLUSION: Infiltrating endometriotic lesions appear to originate intraperitoneally sharing common pathogenetic mechanisms. Involvement of the intestinal and urologic apparatuses should be identified before surgery, in order to schedule intraoperative consultation and to inform the woman about the type of intervention required and its potential sequelae. Copyright 2009 S. Karger AG, Basel.
Fertil Steril. 2009 Jul;92(1):391.e5-7. Epub 2009 May 23.
Renal endometriosis presenting with a giant subcapsular hematoma: case report.
Department of Urology, Baskent University School of Medicine, Ankara, Turkey.
OBJECTIVE: To describe a case of renal subcapsular hematoma due to renal endometriosis. DESIGN: Case report. SETTING: Departments of Urology and Pathology, Baskent University Faculty of Medicine, Ankara, Turkey. PATIENT(S): A 46-year-old premenopausal woman was admitted with a left lumbar pain and mass. Ultrasonography and computerized tomography revealed a giant-sized renal subcapsular hematoma. INTERVENTION(S): Computerized tomography, percutaneous drainage catheter placement, surgical exploration, and excision of renal capsule. MAIN OUTCOME MEASURE(S): None. RESULT(S): Histopathologic examination revealed endometriosis located beneath the fibrous renal capsule. CONCLUSION(S): Renal capsular endometriosis should be kept in mind among the causes of renal subcapsular hematoma.
Fertil Steril. 2009 Oct;92(4):1253-5. Epub 2009 May 23.
The second time around: reproductive performance after repetitive versus primary surgery for endometriosis.
Division of Gynecologic Surgery, Istituto Ostetrico e Ginecologico Luigi Mangiagalli, Università degli Studi di Milano, Milan, Italy. firstname.lastname@example.org
After repetitive surgery for recurrent endometriosis, 20 of 89 (22%) women achieved spontaneous pregnancy, compared with 165 of 411 (40%) after first-line procedure (adjusted incidence rate ratio, 0.51; 95% confidence interval, 0.32 to 0.82), and the 12- and 24-month cumulative pregnancy rates were 14% and 26% in the former group compared with 32% and 38% in the latter. Among infertile patients at baseline, 13 of 67 (19%) conceived after reoperation compared with 98 of 290 (34%) after primary surgery (adjusted incidence rate ratio, 0.55; 95% confidence interval, 0.30 to 0.99), and the 12- and 24-month cumulative pregnancy rates were 13% and 22% in the former group and 25% and 30% in the latter.
Reprod Biol Endocrinol. 2009 May 28;7:54.
Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet.
Departamento de Biología Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico. email@example.com
BACKGROUND: Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis. METHODS: Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 microg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month. RESULTS: Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p < 0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group. CONCLUSION: WEN had a lower intake of antioxidants in comparison to WWE. Peripheral oxidative stress markers diminished, and antioxidant markers were enhanced, in WEN after the application of the HAD.
Fertil Steril. 2009 May 26. [Epub ahead of print]
Aberrant gene expression profile in a mouse model of endometriosis mirrors that observed in women.
Department of Obstetrics, Gynecology and Women’s Health, University of Missouri, Columbia, Missouri.
OBJECTIVE: To define the altered gene expression profile of endometriotic lesions in a mouse model of surgically induced endometriosis. DESIGN: Autologous experimental mouse model. SETTING: Medical school department. ANIMAL(S): Adult C57Bl6 mice. INTERVENTION(S): Endometriosis was surgically induced by autotransplantation of uterine tissue to the intestinal mesentery. Endometriotic lesions and eutopic uteri were recovered at 3 or 29 days after induction. MAIN OUTCOME MEASURE(S): Altered gene expression was measured in the endometriotic lesion relative to the eutopic uterus by genome-wide complementary DNA microarray analysis and was confirmed by real-time reverse transcriptase-polymerase chain reaction for six genes. Relevant categories of altered genes were identified using gene ontology analysis to determine groups of genes enriched for altered expression. RESULT(S): The expression of 479 and 114 genes was altered in the endometriotic lesion compared with the eutopic uterus at 3 or 29 days after induction, respectively. Gene ontology enrichment analysis revealed that genes associated with the extracellular matrix, cell adhesions, immune function, cell growth, and angiogenesis were altered in the endometriotic lesion compared with the eutopic uterus. CONCLUSION(S): According to gene expression analysis, the mouse model of surgically induced endometriosis is a good model for studying the pathophysiology and treatment of endometriosis.
Praxis (Bern 1994). 2009 May 27;98(11):603-7.
The use of transvaginal sonography (TVS) for preoperative diagnosis of pelvic endometriosis[Article in German]
Endometriosezentrum Stufe III, Abteilung für Gynäkologie und Geburtshilfe, Landeskrankenhaus Villach. firstname.lastname@example.org
Endometriosis is one the most challenging gynaecological disorders affecting 10-15% of women in their reproductive years. Considerable diagnostic delay of up to 8 years from presenting symptoms often confers a heavy economic and social price. Over the past years, additional diagnostic tools such as transvaginal scanning (TVS) and/or MRI have been recommended as an appropriate investigation to diagnose ovarian endometriomas or adenomyosis. Several lines of recent evidence strongly suggests that the use of TVS also has an important role in detecting DIE of the pelvis not only involving the ovaries but also structures such as the vagina, the rectovaginal space, the uterosacral ligaments, the bladder or the rectal wall.
Urol J. 2009 Spring;6(2):132-4.
Endometriosis with pure urinary symptoms.
Laser in Medical Science Research Center, Shohada-e-Tajrish Hospital, Shahid Beheshti University (MC), Tehran, Iran. email@example.com
Arch Gynecol Obstet. 2009 May 27. [Epub ahead of print]
ABO and Rh blood groups distribution in patients with endometriosis.
Department of Obstetrics and Gynecology, Etlik Zübeyde Hanim Women’s Health Teaching and Research Hospital, Ankara, Turkey, firstname.lastname@example.org.
J Gynecol Oncol. 2009 Mar;20(1):60-2. Epub 2009 Mar 31.
A case of clear cell carcinoma arising from the endometriosis of the paraovarian cyst.
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.
Malignant transformation of endometriosis is an infrequent complication. Clear cell carcinoma from endometriosis is very rare in the paraovarian cyst. To date no cases have been reported. We report a case of clear cell carcinoma arising from endometriosis of the paraovarian cyst with a brief review of literature.
Qual Health Res. 2009 Jul;19(7):985-95. Epub 2009 May 26.
I never know from one day to another how I will feel: pain and uncertainty in women with endometriosis.
Faculty of Health, Birmingham City University, Perry Barr, Birmingham, United Kingdom.
Endometriosis is a chronic condition of women in which endometrial tissue is present outside of the uterus. It is characterized by pelvic pain. The aim of this prospective study was to explore women’s experience of living with endometriosis. A sample of 30 women was recruited from a dedicated endometriosis clinic. Semistructured interviews were conducted upon recruitment and after one year, these data being supplemented by diary keeping by a volunteer sample. As a storytelling approach was utilized for data collection, narrative analysis was considered most appropriate. The findings are presented using the concept of uncertainty, which has been found in previous research to be a feature of long-term illness. Uncertainty exists around diagnosis, the course of the disease, and the future. It is argued that the way in which the pain of endometriosis is interpreted and managed by women and health professionals is integral to this uncertainty.
Eur J Obstet Gynecol Reprod Biol. 2009 Aug;145(2):172-6. Epub 2009 May 20.
Anti-apoptotic and pro-apoptotic gene expression evaluated from eutopic endometrium in the proliferative phase of the menstrual cycle among women with endometriosis and healthy controls.
Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. email@example.com
OBJECTIVE: Endometriosis affects 5-15% of women in the general population and 40% of women seeking infertility evaluation. Its etiology and pathogenesis is controversial. Abnormalities of genes involved in the regulation of apoptosis have been thought to play a role in origin. Hence, we investigated the expression of pro-apoptotic and anti-apoptotic genes in eutopic endometrium from women with endometriosis and healthy controls in relation to disease occurrence and severity. STUDY DESIGN: A prospective study in women undergoing laparoscopic surgery for pelvic pain was conducted. In total, 45 women (30 healthy controls and 15 patients) matched inclusion criteria. The mRNA expression of apoptotic genes (p53, Bcl-x(L,S) and Bax) from eutopic endometrium was detected by RT-PCR. RESULTS: A significant increase in expression of mRNA p53 (1.42 versus 1.02; p<0.05), and Bcl-x(S) (0.41 versus 0.19; p=0.0006) was found in women with endometriosis compared to healthy controls. Insignificantly increased expression was found for Bax (1.22 versus 1.15). The expression of anti-apoptotic Bcl-x(L) was unchanged (1.08 versus 1.07). The Bcl-x(L)/Bcl-x(S) ratio was twofold higher (5.63 versus 2.63) in controls. By stratifying patients by disease stage we have revealed an increased mRNA expression of apoptotic genes in patients with grades III-IV endometriosis compared to those with grades I-II. However, the difference was significant only for Bcl-x(S) expression (p<0.05). CONCLUSIONS: Results suggest that an increased transcription of pro-apoptotic genes (p53 and Bcl-x(S)) in eutopic endometrium is significantly associated with endometriosis, which indicates dysregulation of apoptotic gene transcription associated with disease.
Int J Gynaecol Obstet. 2009 Sep;106(3):198-201. Epub 2009 May 24.
Accuracy of magnetic resonance imaging for diagnosis and preoperative assessment of deeply infiltrating endometriosis.
Fleury Medicina e Saúde, São Paulo, Brazil. firstname.lastname@example.org
OBJECTIVE: To evaluate the accuracy of preoperative magnetic resonance imaging (MRI) findings relative to surgical presence of deeply infiltrating endometriosis (DIE). METHODS: This prospective study included 92 women with clinical suspicion of DIE. The MR images were compared with laparoscopy and pathology findings. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI for diagnosis of DIE were assessed. RESULTS: DIE was confirmed at histopathology in 77 of the 92 patients (83.7%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI to diagnose DIE at each of the specific sites evaluated were as follows: retrocervical space (89.4%, 92.3%, 96.7%, 77.4%, 90.2%); rectosigmoid (86.0%, 92.9%, 93.5%, 84.8%, 89.1%); bladder (23.1%, 100%, 100%, 88.8%, 89.1%); ureters (50.0%, 100%, 95.5%, 95.7%); and vagina (72.7%, 100%, 100%, 96.4%, 96.7%). CONCLUSION: MRI demonstrates high accuracy in diagnosing DIE in the retrocervical region, rectosigmoid, bladder, ureters, and vagina.