Gynecol Obstet Invest. 2010 Feb 2;70(1):23-33. [Epub ahead of print]

Constitutive and Tumor Necrosis Factor-Alpha-Stimulated Activation of Nuclear Factor-KappaB in Immortalized Endometriotic Cells and Their Suppression by Trichostatin A.

Wu Y, Starzinski-Powitz A, Guo SW.

Taussig Cancer Center, Center for Hematology and Oncology Molecular Therapeutics, Cleveland, Ohio, USA.

Objective(s): To determine whether nuclear factor-kappaB (NF-kappaB) is constitutively and tumor necrosis factor (TNF)-dependently activated in endometriotic cells, whether trichostatin A (TSA) can suppress NF-kappaB activation and suppress TRAF2/6 and TAK1, and whether TSA and caffeic acid phenyl ester can suppress constitutive and H(2)O(2)-stimulated proliferation of endometriotic cells. Methods: Two endometriotic cell lines and an endometrial stromal cell line were used as an in vitro model. Electrophoretic mobility shift analysis was used to determine NF-kappaB activation and possible suppression by TSA. Western blot analysis was used to determine whether TSA suppresses phosphorylation of IkappaBalpha, phosphorylation of p65 in the cytoplasm and nuclear translocation, and the expression of TRAF2/6 and TAK1. Results: NF-kappaB was constitutively activated in endometriotic cells, but only minimally in endometrial cells. TNFalpha stimulation activated NF-kappaB through induction of IkappaB phosphorylation, but the activation can be suppressed by TSA. TSA also attenuated constitutive and TNF-dependent p65 phosphorylation and nuclear translocation in endometriotic cells. TRAF2, TRAF6 and TAK1 were constitutively activated and were unaffected by TSA treatment. Conclusions: NF-kappaB activation may play a critical role in the pathogenesis in endometriosis. Targeting NF-kappaB with histone deacetylase inhibitors or other compounds might hold promise as novel therapeutics for endometriosis. Copyright © 2010 S. Karger AG, Basel.

Biol Reprod. 2010 Feb 3. [Epub ahead of print]

Fine Tuning of Endometrial Function by Estrogen and Progesterone Through microRNAs.

Lessey BA.

Progesterone suppresses estrogen at multiple levels in the normal secretory phase endometrium including the induction of microRNAs. If progesterone-stimulated miRNAs are disrupted, expression from the mRNA targets of each miRNA may fail to be suppressed, allowing excessive cell proliferation. In fact, recent work by others is already confirming the hypothesis that miRNAs are diagnostic smoking guns for various diseases like endometriosis. This is an area of intense investigation and one that is worth watching, especially for those interested in the endometrium, infertility, cancer, and even contraception. The study published in Biology of Reproduction by Kuokkanen et al. on miRNA expression in endometrial epithelium sets the stage to look for miRNAs as a mechanism for progesterone resistance at the subcellular level.COMMENTARY for: Genomic Profiling of MicroRNAs and Messenger RNAs Reveals Hormonal Regulation in MicroRNA expression in Human Endometrium by Satu Kuokkanen, Bo Chen, Laureen Ojalvo, Lumie Benard, Nanette Santoro, and Jeffrey W. Pollard. Biol Reprod e-pub ahead of print October 28, 2009, doi:10.1095/biolreprod.109.081059.

Hum Reprod. 2010 Feb 3. [Epub ahead of print]

Surgery for bladder endometriosis: long-term results and concomitant management of associated posterior deep lesions.

Chapron C, Bourret A, Chopin N, Dousset B, Leconte M, Amsellem-Ouazana D, de Ziegler D, Borghese B.

Department of Gynecology, Obstetrics II and Reproductive Medicine, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Saint Vincent de Paul, Pavillon Lelong, 82 avenue Denfert Rochereau, 75014 Paris, France.

BACKGROUND Deep infiltrating endometriosis (DIE) is presented as a disease with high recurrence risk. Bladder DIE is the most frequent location in cases of urinary endometriosis. Surgical removal has been recommended for bladder DIE but long-term outcomes remains unevaluated. The objectives of this study are to evaluate the rate of recurrence after partial cystectomy for patients presenting with bladder DIE and to outline the surgical modalities for handling associated posterior DIE nodules. METHODS Seventy-five consecutive patients with histologically proved bladder DIE were enrolled at a single tertiary academic center between June 1992 and December 2007. A partial cystectomy was performed for each patient. Complete surgical exeresis of all associated symptomatic DIE lesions was carried out during the same surgical procedure. Bladder DIE patients were classified into three groups: patients with isolated bladder DIE (Group A); patients with associated symptomatic posterior DIE (Group B); patients with associated asymptomatic posterior DIE (Group C). Bladder DIE recurrence was defined as a clinical reappearance of the disease or radiological evidence that mandated a new surgical procedure. We assessed pelvic pain symptoms pre- and post-operatively using a 10-cm visual analogue scale. RESULTS In a series of 627 patients with DIE, we observed 75 patients (12%) with bladder DIE. With a 50.9 +/- 44.6 months mean follow-up after partial cystectomy no patient presented evidence of bladder DIE recurrence. Post-operatively, we observed a significant improvement with respect to pain symptoms, with only two patients (2.7%) developing major complications during follow-up. Among patients with non-operated associated asymptomatic posterior DIE lesions (n = 15), a second surgical procedure indicated for pain symptoms was necessary in only one patient (6.7%). CONCLUSIONS For patients presenting with bladder DIE, no patients required further surgery for bladder recurrence after radical surgery consisting in partial cystectomy. Exeresis of associated posterior DIE nodules is indicated only when they are symptomatic.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):124-7.

Laparoscopic approach to right diaphragmatic endometriosis with argon laser: case report.

Gilabert-Estelles J, Zorio E, Castello JM, Estelles A, Gilabert-Aguilar J.

Unit of Gynecologic Endoscopy, Hospital Casa de Salud, Valencia, Spain. juangilaeste@yahoo.es

Diaphragmatic involvement by an endometriotic cyst is a rare entity that may be responsible for chronic thoracic pain. Herein we present a case report of a 6-cm right diaphragmatic endometrioma treated using laparoscopic partial excision and argon laser coagulation of the inner cyst wall. The laparoscopic approach to upper abdomen endometriosis is feasible and safe when accurate evaluation of the case is performed. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):110-2.

Internal herniation of adnexa through a defect of the broad ligament: case report and literature review.

Demir H, Scoccia B.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Illinois College of Medicine, Chicago, IL 60612-7313, USA.

Internal herniation through a defect of the broad ligament occurs rarely. Herniation of the ovary rather than the small intestine or colon is extremely rare. We present only the third known case of herniation of the adnexa into a broad ligament defect. A 42-year-old woman, gravida 3, para 2, aborta 1, had severe continuing right lower quadrant pain that was resistant to medical and surgical treatments. The clinical history was significant for long-standing endometriosis, 2 previous laparoscopic procedures to treat endometriosis, and chronic pelvic pain despite medical and surgical treatments. At the second laparoscopic procedure, pelvic endometriosis was excised, and a large defect of the right broad ligament was noted but not treated. At the third operation, right salpingo-oophorectomy was performed to eliminate the large broad ligament defect and the possibility of internal herniation on the right side as a possible explanation for the patient’s chronic right lower quadrant pain. Postoperatively, the pain resolved, and the patient has been pain-free for 9 months. This type of internal herniation should be considered in the differential diagnosis in female patients with pelvic pain. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):107-9.

Laparoscopic resection of endometriosis in a patient with a ventriculoperitoneal shunt using the LapDisc.

Orbuch IK, Atkin R, Filmar G, Singer T, Divon MY.

Department of Obstetrics and Gynecology, Lenox Hill Hospital, New York, New York 10012, USA. irisorbuch@gmail.com

The surgical approach in a patient with a ventriculoperitoneal shunt in need of abdominal surgery remains controversial. The risk of increased intracranial pressure with pneumoperitoneum in laparoscopy is still unresolved. We used the LapDisc (Ethicon, Inc., Somerville, New Jersey) to access the shunt and temporarily seal it, which enabled us to perform laparoscopic resection of endometriosis without subjecting the shunt to high intraabdominal pressure. The benefits of this approach are the ability to perform laparoscopy, less skin-to-shunt contact minimizing infection, and elimination of possible increased intracranial pressure secondary to pneumoperitoneum. With the progress made in the management of hydrocephalus, patients with ventriculoperitoneal (VP) shunts enjoy a longer lifespan. Therefore, the gynecologic laparoscopic surgeon can expect to treat a patient with a VP shunt in place. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):100-3.

Surgical management of recurrent ureteric endometriosis causing recurrent hypertension in a postmenopausal woman.

Khong SY, Lam A, Coombes G, Ford S.

Centre for Advanced Reproductive Endosurgery, St. Leonards NSW, Australia. su-yen@sydneycare.com.au

Endometriosis is a common condition that affects as many as 10% to 20% of women of reproductive age. Because of the subtle clinical signs and symptoms and limitations of imaging methods, the diagnosis is frequently delayed or missed, with serious consequences including hypertension, hydronephrosis, and loss of kidney function. We present an unusual case of recurrent ureteric endometriosis in a postmenopausal woman to highlight the challenges of screening for and management of endometriosis. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):42-6.

Surgical treatment of endometriosis in private practice: cohort study with mean follow-up of 3 years.

Roman JD.

Braemar Hospital, Hamilton, New Zealand.

STUDY OBJECTIVE: To describe our experience with surgical treatment of endometriosis. DESIGN: Observational cohort study (Canadian Task Force classification II-2). SETTING: Private hospital. PATIENTS: One hundred sixty-three patients with histologically confirmed endometriosis who had completed a preoperative questionnaire, had available intraoperative findings and photographic documentation, and had been followed up to 6 years. INTERVENTION: Laparoscopic electrosurgical excision of endometriotic implants. MEASUREMENTS AND MAIN RESULTS: Patients completed a visual analogue scale (VAS) for 6 components of endometriosis-related symptoms. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life. Long-term follow up was performed using a questionnaire and review of patient medical records. Mean (SD; 95% confidence interval) patient age at surgery was 31.01 (8.5; 29.7-32.3) years. The primary symptom at initial consultation was dysmenorrhea in 94 patients (57.67%, nonmenstrual pelvic pain in 44 (27%), dyspareunia in 11 (6.75%), menorrhagia in 8 (4.9%), infertility in 4 (2.45%), and pelvic mass in 2 (1.23%). Thirty-three patients (20%) had undergone previous surgery because of endometriosis. At surgery, endometriosis was stage I in 50 patients (30.67%), stage II in 65 (39.88%), stage III in 23 (14.11%), and stage IV in 25 (15.34%). Other surgical procedures performed with the index surgery were cystoscopy in 48 patients (29.45%), laparoscopic ovarian cystectomy in 24 (14.72%), laparoscopic hysterectomy in 15 (9.2%), laparoscopic appendectomy in 9 (5.5%), sigmoidoscopy in 6 (3.68%), laparoscopic oophorectomy in 6 (3.68%), extensive laparoscopic adhesiolysis in 5 (3.07%) bowel resection in 2 (1.25%), laparoscopic myomectomy in 1 (0.61%), and bladder resection in 1 (0.61%). Surgery proceeded to laparotomy in 6 patients (3.68%). Major surgical complications included bowel perforation, severe pelvic pain 1 week after laparoscopic excision, and temporary numbness of the right side of the perineum in 1 patient each. Minor postoperative complications included urinary tract infection in 3 patients and port site infections that resolved with oral antibiotic therapy in 2 patients. Follow-up was 37.82 (20.09; 34.74-40.92) months. Surgical excision of endometriosis had a positive effect on endometriosis-related symptoms. Four pain scores were reduced, with statistically significant differences (p<.001 and p<.05): dysmenorrhea, pelvic pain not related to menstruation, dyspareunia, and dyschezia. The positive effect of surgical excision on patient quality of life was demonstrated by a statistically significant difference on the EQ-5D index (p<.001) and the EQ-5D VAS (p<.001). Thirty-two (20%) patients underwent a second procedure after the index surgery. Endometriosis stage affects the probability of requiring further surgery because of recurrent symptoms. There was evidence of endometriosis at histologic analysis in only 13 (40.62%) patients who required further surgery. CONCLUSION: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life as measured by both the EQ-5D index and the EQ-5D VAS, with a low complication rate. Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.

J Minim Invasive Gynecol. 2010 Jan-Feb;17(1):14-5.

Nerve-sparing laparoscopic radical excision of deep endometriosis with rectal and parametrial resection.

Ceccaroni M, Pontrelli G, Scioscia M, Ruffo G, Bruni F, Minelli L.

Gynecologic Oncology Division, Department of Obstetrics and Gynecology, European Gynaecology Endoscopy School, Sacred Heart Hospital, Negrar, Verona, Italy.

World J Gastroenterol. 2010 Feb 7;16(5):648-51.

Rectal perforation from endometriosis in pregnancy: case report and literature review.

Pisanu A, Deplano D, Angioni S, Ambu R, Uccheddu A.

Department of Surgery, Clinica Chirurgica, University of Cagliari, Ospedale San Giovanni di Dio, Via Ospedale 46, 09124, Cagliari, Italy. adolfo.pisanu@unica.it

This case report describes a woman with spontaneous rectal perforation from decidualized endometriosis in pregnancy. A 37-year-old woman was admitted to our hospital at 30 wk of pregnancy with symptoms suggestive of pyelonephritis, which persisted until 33 wk of gestation when delivery of a premature male baby was performed through a cesarean section. On postoperative day 2, an abdominal computed tomography showed free air in the peritoneal cavity and a pelvic abscess. Explorative celiotomy revealed a diffuse severe fecaloid peritonitis that originated from a 3-cm wide rectal perforation. A Hartmann operation was then performed. Histopathological findings were consistent with decidualization of the rectal wall. Only 20 cases of intestinal perforation due to endometriosis have been reported in the literature. This report is believed to be the first case of spontaneous rectal perforation from endometriosis in pregnancy, and it shows the potential occurrence of serious and unexpected complications of the disease.

Curr Med Res Opin. 2010 Feb 3. [Epub ahead of print]

An observational study of assisted reproductive technology outcomes in new European Union member states: an overview of protocols used for ovarian stimulation.

Vlaisavljević V, Meden-Vrtovec H, Lewandowski P, Radwan M, Langerova A, Vicena M, Války J, Herman M, Usoniene A, Treijs G.

Department of Reproductive Medicine, University Clinical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia.

Abstract Background: The development of new fertility treatment options has facilitated individualized assisted reproductive technology (ART) protocols to improve outcomes. Manufacturing improvements to recombinant human follitropin alfa have allowed precise dosing based on mass (filled-by-mass; FbM) rather than bioactivity (filled-by-bioassay; FbIU). Continued monitoring and reporting of follitropin alfa treatment outcomes in routine clinical practice is essential. Objective: To provide an overview of the frequency of different controlled ovarian-stimulation protocols used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in new European Union member states, and to provide post-registration efficacy and safety data on follitropin alfa. Research design and methods: A 2-year, prospective, observational, multicentre, Phase IV study conducted at ART clinics in the Czech Republic, Estonia, Latvia, Lithuania, Poland, Slovakia and Slovenia. Women aged 18-47 years undergoing ovarian stimulation with follitropin alfa for conventional IVF or ICSI were eligible for inclusion. The main treatment outcome was cumulative clinical pregnancy rate. Data were analysed descriptively. Results: Clinical pregnancy outcomes were available for 4055 of 4085 (99.3%) patients. In total, 1897 (46.8%) patients used follitropin alfa FbIU; 2133 (52.6%) used follitropin alfa FbM. Clinical pregnancy was achieved by 39.5% (1603/4055) of patients. A greater proportion of patients with polycystic ovary syndrome achieved a clinical pregnancy than those with endometriosis (41.8% vs 37.8%, respectively). A higher cumulative pregnancy rate was observed with the use of follitropin alfa FbM than follitropin alfa FbIU (41.3% vs 37.8%, respectively; p = 0.02). Conclusions: This study represents the most comprehensive audit of individualized ART in clinical practice in Central and Eastern Europe. Overall, clinical pregnancy was achieved by 39.5% of patients after stimulation with follitropin alfa. The use of follitropin alfa FbM resulted in a higher cumulative pregnancy rate than did the FbIU formulation. However, limitations of the study include the observational and non-comparative study design, and descriptive nature of statistical analyses; furthermore, the study was not designed to make direct comparisons between the success rates of different ovarian-stimulation protocols.

Hum Reprod. 2010 Jan 29. [Epub ahead of print]

Trichostatin A, a histone deacetylase inhibitor, reduces lesion growth and hyperalgesia in experimentally induced endometriosis in mice.

Lu Y, Nie J, Liu X, Zheng Y, Guo SW.

Shanghai OB/GYN Hospital, Fudan University, Shanghai, China.

BACKGROUND The aim of this study was to evaluate the effect of trichostatin A (TSA) in a mouse model of endometriosis on serum tumour necrosis factor alpha (TNFalpha) levels, hotplate latency, lesion size and immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5. METHODS We used 30 adult female mice, and endometriosis was induced by auto-transplanting pieces of uterus (ENDO) or fat (SHAM) to peritoneum in lower parts of the abdominal and pelvic cavity. Two weeks later, the ENDO group was further divided into two groups randomly: one received TSA treatments and the other received injections of dimethyl sulfoxide, as did the SHAM mice. Four weeks later, all mice were sacrificed. Response latency in hotplate test and serum TNFalpha levels were measured before the surgery, and before and after the treatment, along with the average lesion size and the immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5, in both eutopic and ectopic endometrium and vaginal tissue. RESULTS We found that mice receiving TSA had a significantly reduced average lesion size as compared with untreated mice, as well as a significant improvement in response to a noxious thermal stimulus. They also had a significantly lower immunoreactivity to Trpv1 in eutopic endometrium, to Pkcepsilon in ectopic endometrium and to Pgp9.5 in vagina. CONCLUSIONS Endometriosis causes increased central sensitivity to noxious stimuli. Treatment with TSA significantly reduces lesion growth and may relieve pain symptoms in women with endometriosis, indicating that histone deacetylase inhibitors may be a promising therapeutic agent.

Eur J Radiol. 2010 Jan 28. [Epub ahead of print]

Ultrasound-guided high-intensity focused ultrasound treatment for abdominal wall endometriosis: Preliminary results.

Wang Y, Wang W, Wang L, Wang J, Tang J.

Department of Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.

PURPOSE: To evaluate the safety and therapeutic efficacy of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) ablation for the treatment of abdominal wall endometriosis (AWE). MATERIALS AND METHODS: Twenty-one consecutive patients with AWE were treated as outpatients by US-guided HIFU ablation under conscious sedation. The median size of the AWE was 2.4cm (range 1.0-5.3cm). An acoustic power of 200-420W was used, intermittent HIFU exposure of 1s was applied. Treatment was considered complete when the entire nodule and its nearby 1cm margin become hyperechoic on US. Pain relief after HIFU ablation was observed and the treated nodule received serial US examinations during follow-up. RESULTS: All AWE was successfully ablated after one session of HIFU ablation, the ablation time lasted for 5-48min (median 13min), no major complications occurred. The cyclic pain disappeared in all patients during a mean follow-up of 18.7 months (range 3-31 months). The treated nodules gradually shank over time, 16 nodules became unnoticeable on US during follow-up. CONCLUSION: US-guided HIFU ablation appears to be safe and effective for the treatment of AWE. Copyright © 2010. Published by Elsevier Ireland Ltd.

Reprod Biomed Online. 2010 Feb;20(2):300-302. Epub 2009 Dec 3.

Combined technique of excision and ablation for the surgical treatment of ovarian endometriomas: the way forward?

Muzii L, Panici PB.

Department of Gynecology, Università Campus BioMedico, Rome, Italy.

Surgical treatment of ovarian endometriosis has been associated with damage to the ovarian tissue and premature ovarian failure in young patients. A modified surgical technique that combines cyst excision with ablation for the surgical treatment of ovarian endometriomas is presented, with the aim of reducing possible damage to the ovarian tissue without jeopardizing the results of surgery in terms of subsequent pregnancies and symptom relief. The modified technique is a combination of the excision technique, adopted for most of the procedure, with the coagulation technique, adopted at the ovarian hilus to better preserve normal ovarian tissue and vascularization of the ovary. Postoperative follow-up of patients operated on with this modified technique indicates that the technique is feasible and safe, with no apparent damage to the ovary. Copyright © 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Reprod Biomed Online. 2010 Feb;20(2):286-290. Epub 2009 Nov 26.

CYP17 and CYP2C19 gene polymorphisms in patients with endometriosis.

Bozdag G, Alp A, Saribas Z, Tuncer S, Aksu T, Gurgan T.

Department of Obstetrics and Gynecology, Hacettepe University, School of Medicine, Hacettepe, 06100 Ankara, Turkey.

Endometriosis seems to be the result of a complex interaction between environmental factors and various genes. In this regard, the cytochrome subfamily 17 (CYP17) may play an important role by altering the biosynthesis of sex steroids. CYP2C19 is also an important member of the cytochrome P450 (CYP) family, and related mutations may result in an inability to fully metabolize environmental chemicals and cytokines, leading to several diseases. This study sought to determine whether there is a relationship between endometriosis and CYP17 T>C, CYP2C19 *2 and CYP2C19 *3 polymorphisms. When samples from 46 patients with endometriosis and 39 healthy controls were analysed, A2A2 type mutation of the CYP17 gene was observed to be more frequent in patients with endometriosis (34.8 versus 7.7%, P=0.003). No association was found between the severity of endometriosis and CYP2C19 *2 or CYP2C19 *3 polymorphisms of the CYP2C19 gene. These results suggest that mutations related with sex steroid metabolism seem to have an important role in endometriosis. However, the relation between detoxification ability and endometriosis should be examined in further studies with larger sample sizes. Copyright © 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Thorac Surg Clin. 2009 Nov;19(4):521-9.

Tumors of the diaphragm.

Kim MP, Hofstetter WL.

Division of Thoracic and Cardiovascular Surgery, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Unit 445, Houston, TX 77030-4009, USA.

Primary tumors of the diaphragm are rare. The most common benign cystic lesions of the diaphragm are bronchogenic or mesothelial cysts, while the most common benign solid lesion is a lipoma. Benign tumors of the diaphragm are resected if they are symptomatic or if there is a doubt about the diagnosis. The most common primary malignant lesion is rhabdomyosarcoma. Malignant tumors are treated based on histology and often with chemotherapy and/or radiation along with surgical resection if feasible. Endometriosis, a benign process that metastasizes to the diaphragm, is typically treated medically; surgical ablation or resection is considered only after failed conservative treatment. Surgical resection of metastatic malignant tumors, such as ovarian cancer and thymoma, as well as malignancies affecting the diaphragm by direct extension, such as mesothelioma, lung, and esophageal cancer, may provide some survival advantage.

J Tradit Chin Med. 2009 Dec;29(4):296-300.

Effect of Yikun Neiyi Wan on the expression of aromatase P450, COX-2, and ER related receptor in endometrial cells in vitro from patients with endometriosis.

Wang Q, Zhao H, Xiang Q, Ju H, Han SM, Wang LY, Xu B.

Department of TCM Gynecology, China-Japan Friendship Hospital, Beijing 100029, China.

OBJECTIVE: To investigate the effect of yikun neiyi wan (YKNYW) and gestrinone on the expression of aromatase P450 (P450arom), cyclo-oxygenase-2 (COX-2) and estrogen receptor (ER) in isolated ectopic and normal endometrial stroma cells in vitro. METHODS: Digestion and serial filtration were used to isolate and culture the ectopic and eutopic endometrial cells from patients with chocolate cyst in virto. Transformation of the cell morphology was observed in a inverted microscope. The effect of YKNYW on the expression of aromatase P450, cyclo-oxygenase-2, estrogen receptor in cultured endometriosis cells were detected by immunohistochemical method. RESULTS: The expression levels of P450arom, COX-2 in glandular epithelium cells in vitro were decreased significantly by YKNYW compared with gestrinone (P < 0.05). ER expression in mesenchymal cells of endometriosis was increased by YKNYW in the large and medium dosage groups compared with gestrinone. CONCLUSION: The mechanism by which YKNYW alleviates endometriosis pain is possibly related to the decrease in ectopic endometrial P450 arom and COX-2 expression in glandular epithelium, contrary to gestrinone, and the increase in ER expression in mesenchymalis, consistent with gestrione in patients with endometriosis.

J La State Med Soc. 2009 Nov-Dec;161(6):321-4.

Endometriosis in the rectus abdominis muscle: case report and literature review.

Kandil E, Alabbas H, Ghafar M, Burris K, Sawas A, Schwartzman A.

Department of Surgery, Tulane University Medical Center, New Orleans, USA.

Endometriosis is characterized by the presence of histologically normal endometrial tissue outside the uterine cavity. Endometriosis occurs most commonly within the pelvis. Extrapelvic endometriosis is less common, but can involve nearly every organ in the body. We present a patient in whom endometriosis was discovered in the rectus abdominis muscle and discuss the imaging findings and histopathology.

Semin Reprod Med. 2010 Jan;28(1):44-50.

17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis.

Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, Thung S, Xue Q, Marsh EE, Tokunaga H, Ishikawa H, Kurita T, Su EJ.

Division of Reproductive Biology Research, Department Obstetrics and Gynecology Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-bulun@northwestern.edu

Estradiol (E2) stimulates the growth and inflammation in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Several clinical and laboratory-based observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptor (PR). In normal endometrium, progesterone acts via PR on stromal cells to induce secretion of paracrine factor(s) that in turn stimulate neighboring epithelial cells to express the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (HSD17B2). HSD17B2 is an extremely efficient enzyme and rapidly metabolizes the biologically potent estrogen E2 to weakly estrogenic estrone. In endometriotic tissue, progesterone is incapable of inducing epithelial HSD17B2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate HSD17B2 may be due to the very low levels of PR observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this mitogen. The molecular details of this physiological paracrine interaction between the stroma and epithelium in normal endometrium and its lack thereof in endometriosis are discussed.

Hum Reprod. 2010 Jan 26. [Epub ahead of print]

Delayed functional outcomes associated with surgical management of deep rectovaginal endometriosis with rectal involvement: giving patients an informed choice.

Roman H, Loisel C, Resch B, Tuech JJ, Hochain P, Leroi AM, Marpeau L.

Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France.

BACKGROUND The aim of this study was to compare delayed functional digestive and urinary outcomes following two different surgical procedures used in the management of rectal endometriosis. METHODS Women who had undergone surgical management of rectal endometriosis with at least 1 year of post-operative follow-up were included in a retrospective study. Post-operative symptoms were evaluated using specific questionnaires which focused on pelvic pain and functional outcomes. RESULTS There were 41 women who underwent surgical treatment of symptomatic rectal endometriosis. Post-operative follow-up was completed over 26 +/- 13 months (range 12-53). Colorectal segmental resection was performed in 25 women (61%) and nodule excision in 16 (39%). An increase in the number of daily stools >/=3 was observed in 13 (52%) and 3 (19%) patients managed, respectively, by segmental resection and nodule excision (P = 0.02). Severe constipation (<1 stool/5 days) was recorded in three women having undergone segmental resection. The probabilities of being free of dysmenorrhea, dyspareunia and non-cyclic pain at 24 months in women managed by segmental resection and nodule excision were, respectively, 80% (95% CI: 55-92%), 65% (95% CI: 42-81%), 43% (95% CI: 23-62%) and 62% (95% CI: 34-81%), 81% (95% CI: 52-94), 69% (95% CI: 40-86%). When pain recurrences occurred, a significantly lower post-operative score for pain was observed in both groups. No significant difference in pain improvement was found between surgical procedures. CONCLUSION Colorectal segmental resection appears to be associated with several unpleasant functional symptoms when compared with nodule excision. Information about functional outcomes should be provided to patients managed for rectal endometriosis, and should be considered when deciding on the most appropriate treatment of this disease.

Semin Reprod Med. 2010 Jan;28(1):75-80. Epub 2010 Jan 26.

Progesterone resistance in a baboon model of endometriosis.

Fazleabas AT.

Department of Obstetrics and Gynecology, and Reproductive Biology, College of Medicine, Michigan State University, Grand Rapids, Michigan 49503, USA. ASGI@HC.MSU.EDU

The development of a baboon model of induced endometriosis, which recapitulates the retrograde menstruation hypothesis, has greatly facilitated our understanding of the early events associated with the disease process. Sequential analysis of the eutopic endometrium following the establishment of disease suggests that the development of progesterone resistance is a gradual process and becomes evident after 6 months of disease induction. This resistance is manifested by a decreased responsiveness of the progesterone receptor and its chaperone immunophilins as well as epigenetic modifications of progesterone-regulated genes. In comparative studies, the time-dependent changes observed in the baboon eutopic endometrium are similar to those that have been reported to be altered in women with endometriosis. The baboon model therefore provides insight into the potential mechanisms by which genes in the eutopic endometrium are dysregulated and how this alteration results in infertility that is associated with endometriosis.

Semin Reprod Med. 2010 Jan;28(1):69-74. Epub 2010 Jan 26.

Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions.

Cakmak H, Taylor HS.

Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis. In endometriosis, altered progesterone receptor expression or diminished activity may lead to attenuated or dysregulated progesterone response and decreased expression of progesterone-responsive genes including HOX genes in the eutopic endometrium. In turn, other mediators of endometrial receptivity that are regulated by HOX genes, such as pinopodes, alphavbeta3 integrin, and IGFBP-1, are downregulated in endometriosis. HOXA10 hypermethylation has recently been demonstrated to silence HOXA10 gene expression and account for decreased HOXA10 in the endometrium of women with endometriosis. Silencing of progesterone target genes by methylation is an epigenetic mechanism that mediates progesterone resistance. The relatively permanent nature of methylation may explain the widespread failure of treatments for endometriosis-related infertility.

Semin Reprod Med. 2010 Jan;28(1):59-68. Epub 2010 Jan 26.

Dioxin and endometrial progesterone resistance.

Bruner-Tran KL, Ding T, Osteen KG.

Department of Obstetrics and Gynecology, Women’s Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2519. Kaylon.bruner-tran@vanderbilt.edu

Development of endometriosis likely requires multiple, interactive mechanisms involving both the endocrine and immune systems. Environmental toxicants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are of particular interest as potential contributory agents in the development of this disease because they can disrupt both systems. Nevertheless, defining the potential role that environmental exposure to TCDD plays in the development of endometriosis requires a better understanding of how this toxicant affects the biological processes that promote the disease. Although the disease mechanism(s) responsible for progesterone resistance in the endometrium of endometriosis patients remains speculative, our studies indicate that developmental exposure of mice to TCDD leads to a progesterone-resistant phenotype in adult animals that can persist for several generations. These studies and others underscore the importance of developing a greater understanding of the mechanisms of TCDD action that relate to reproductive disorders such as endometriosis.

Semin Reprod Med. 2010 Jan;28(1):51-8. Epub 2010 Jan 26.

Altered gene expression profiling in endometrium: evidence for progesterone resistance.

Aghajanova L, Velarde MC, Giudice LC.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0132, USA.

Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has been implicated in several gynecologic disorders, including endometriosis, polycystic ovarian syndrome (PCOS), and endometrial hyperplasia. Although several investigators have analyzed eutopic endometrial expression of progesterone-target genes, the genesis and consequences of progesterone resistance remain unclear. We review evidence for progesterone resistance in endometrium of women with endometriosis, PCOS, and endometrial hyperplasia, and we identify possible mechanisms associated with reduced progesterone activity in endometrium of (some) women with these gynecologic disorders that have a significant impact on women’s health and well-being.

Semin Reprod Med. 2010 Jan;28(1):36-43. Epub 2010 Jan 26.

Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis.

Bulun SE, Cheng YH, Pavone ME, Xue Q, Attar E, Trukhacheva E, Tokunaga H, Utsunomiya H, Yin P, Luo X, Lin Z, Imir G, Thung S, Su EJ, Kim JJ.

Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-bulun@northwestern.edu

Loss of progesterone signaling in the endometrium may be a causal factor in the development of endometriosis, and progesterone resistance is commonly observed in women with this disease. In endometriotic stromal cells, the levels of progesterone receptor (PR), particularly the PR-B isoform, are significantly decreased, leading to a loss of paracrine signaling. PR deficiency likely underlies the development of progesterone resistance in women with endometriosis who no longer respond to progestin therapy. Here we review the complex epigenetic and transcriptional mechanisms leading to PR deficiency. The initial event may involve deficient methylation of the estrogen receptor (ER)beta promoter resulting in pathologic overexpression of ERbeta in endometriotic stromal cells. We speculate that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERbeta and ERalpha leading to PR loss and progesterone resistance in endometriosis.

Semin Reprod Med. 2010 Jan;28(1):27-35. Epub 2010 Jan 26.

Epithelial-stromal interaction and progesterone receptors in the mouse uterus.

Rubel CA, Jeong JW, Tsai SY, Lydon JP, Demayo FJ.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Healthy uterine function depends on the balanced interaction of the ovarian steroids estrogen and progesterone (P4) signaling through their respective receptors. The expression of each receptor is regulated by the other through crucial cross talk between the epithelial and stromal compartments. Ablation of the progesterone receptor (PR) results in complete infertility in mice, and evidence increasingly demonstrates that the PR is a major mediator of epithelial-stromal cross talk and events leading to the disruption of this communication can lead to P4 resistance in the uterus. This resistance, through impaired P4 signaling, can be at the level of the PR itself, coregulators, and downstream effectors. The mechanisms underlying P4 resistance is of critical importance in women’s health because this defect is seen in a wide variety of diseases including infertility, endometriosis, endometrial carcinoma, polycystic ovarian syndrome, and leiomyomas. By using mouse models of PR signaling, many of these mechanisms are beginning to be elucidated and aid in the development of effective therapies for treatment of uterine diseases.

Semin Reprod Med. 2010 Jan;28(1):17-26. Epub 2010 Jan 26.

Endometrial decidualization: of mice and men.

Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK.

Department of Cell and Developmental Biology, University of Illinois-Urbana-Champaign, Urbana, Illinois 61801, USA.

In murine and human pregnancies, embryos implant by attaching to the luminal epithelium and invading into the stroma of the endometrium. Under the influence of the steroid hormones estrogen and progesterone, the stromal cells surrounding the implanting embryo undergo a remarkable transformation event. This process, known as decidualization, is an essential prerequisite for implantation. It comprises morphogenetic, biochemical, and vascular changes driven by the estrogen and progesterone receptors. The development of mutant mouse models lacking these receptors has firmly established the necessity of steroid signaling for decidualization. Genomic profiling of mouse and human endometrium has uncovered a complex yet highly conserved network of steroid-regulated genes that supports decidualization. To advance our understanding of the mechanisms regulating implantation and better address the clinical challenges of infertility and endometrial diseases such as endometriosis, it is important to integrate the information gained from the mouse and human models.

Semin Reprod Med. 2010 Jan;28(1):5-16. Epub 2010 Jan 26.

Progesterone function in human endometrium: clinical perspectives.

Young SL, Lessey BA.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina, Chapel Hill 27599-7570, North Carolina, USA. youngs@med.unc.edu

Progesterone is essential for endometrial receptivity and successful establishment of pregnancy. Either an insufficient progesterone concentration or an insufficient response to progesterone, therefore can lead to infertility and pregnancy loss. Assessment of the role that either progesterone insufficiency or inadequate progesterone response plays in human reproductive failure has been difficult to assess because serum progesterone concentrations fluctuate markedly, limiting the ability to characterize sufficiency of progesterone, and there are no highly reliable markers of endometrial function available. Recent evidence demonstrates exquisite sensitivity of normal endometrium to very low levels of progesterone stimulation, suggesting that progesterone insufficiency should not be a common cause of reproductive failure. Further evidence suggests that women with endometriosis, and possibly polycystic ovarian syndrome, have an altered progesterone response, which may explain some of the clinical features of these disorders and supports the hypothesis that progesterone resistance underlies some cases of human reproductive failure.

Contraception. 2010 Feb;81(2):117-22. Epub 2009 Sep 16.

Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue.

Ferreira RA, Vieira CS, Rosa-E-Silva JC, Rosa-e-Silva AC, Nogueira AA, Ferriani RA.

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

BACKGROUND: The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. STUDY DESIGN: This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. RESULTS: After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean+/-SD) of VCAM (92.8+/-4.2 to 91.2+/-2.7 ng/mL, p=.04), CRP (0.38+/-0.30 to 0.28+/-0.21 mg/dL, p=.03), total cholesterol (247.0+/-85.0 to 180.0+/-31.0 mg/dL, p=.0002), triglycerides (118.0+/- 76.0 to 86.5+/-41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5+/-66.0 to 114.5+/-25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0+/-20.5 to 48.5+/-10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5+/-2.9 to 13.0+/-2.7 mumol/L, p=.04) and a reduction in IL-6 levels (4.3+/-3.9 to 2.3+/-0.8 pg/mL, p=.005), VCAM (94.0+/-3.8 to 92.0+/-1.6 ng/mL, p=.03) and total leukocytes (7330+/-2554 to 6350+/-1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. CONCLUSIONS: This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment.

Clin Exp Obstet Gynecol. 2009;36(4):263-4.

Spontaneous umbilical endometriosis: a case report with one-year follow-up.

Spaziani E, Picchio M, Di Filippo A, De Cristofano C, Ceci F, Stagnitti F.

Department of Surgery, University of Rome “Sapienza”, Polo Pontino, Terracina, Latina, Italy.

Umbilical endometriosis is a very rare disease. We report a case of spontaneous umbilical endometriosis in a 36-year old female. Endometriosis was suspected because of the presence of the typical cyclic bleeding and swelling. Abdominal CT excluded the presence of other endometriotic localizations. The umbilical mass was widely excised together with the umbilicus, fascia and peritoneum. The ensuing defect was primarily closed without using prosthetic mesh. Postoperative recovery was uneventful. Histological examination of the specimen showed the presence of endometrial glands with a stromal component, compatible with the diagnosis of endometriosis. At one-year follow-up the results of surgery were satisfactory with no sign of endometriosis recurrence and or parietal defect occurrence. We suggest that surgical excision should be wide in order to prevent local recurrence, and prosthetic materials should not be used to repair the ensuing umbilical defect.

Clin Exp Obstet Gynecol. 2009;36(4):254-5.

Prevalence of acute hemoperitoneum in patients with endometriotic ovarian cysts: a 7-year retrospective study.

Evangelinakis N, Grammatikakis I, Salamalekis G, Tziortzioti V, Samaras C, Chrelias C, Kassanos D.

3rd Department of Obstetrics and Gynecology, Medical School of Athens, General University Hospital “Attikon”, Athens, Greece. evangelinakisnikos@yahoo.gr

INTRODUCTION: Endometriosis is a quite common condition in women of reproductive age. The purpose of this study is to delineate the association between hemoperitoneum and endometriosis. MATERIALS & METHODS: The records of all patients with endometriotic ovarian cysts treated at the 3rd Department of Obstetrics and Gynecology of the University of Athens and at “Lito” Maternity Hospital of Athens from 2000 through 2007 were reviewed. RESULTS: During this 7-year period 720 women underwent surgery due to endometriotic ovarian cysts. The average age was 40.9 years (range: 17-70). The median diameter of the cysts was 4.49 cm and 59% were located in the right ovary. Hemoperitoneum was identified in 16 (2.22%) of them. The average age of these women was 28.5 years (range: 22-44). Ten (62.5%) of these women presented with acute and strong abdominal pain and moderate signs of cardiovascular shock. The rest presented with abdominal pain and distension worsening at the onset of menses, nausea and/or vomiting and hemorrhagic fluid in the pelvis. Ultrasound examination was performed in all women and afterwards they underwent laparoscopy to identify the source of bleeding. In all cases a ruptured endometriotic cyst was found. In 68.8% (11/16) the ruptured cyst was located in the left ovary and the rest (31.2%) in the right. A thorough examination did not reveal any other sources of bleeding. No operative complications were observed. DISCUSSION: The simultaneous occurrence of ascites and endometriosis is rare. A physician, though, must always take into consideration endometriosis in the differential diagnosis of ascites and acute abdominal pain or pelvic mass.

Clin Exp Obstet Gynecol. 2009;36(4):235-6.

Prevalence of severe pelvic inflammatory disease and endometriotic ovarian cysts: a 7-year retrospective study.

Grammatikakis I, Evangelinakis N, Salamalekis G, Tziortzioti V, Samaras C, Chrelias C, Kassanos D.

3rd Department of Obstetrics and Gynecology Medical School of Athens, General University hospital “Attikon”, Athens, Greece.

INTRODUCTION: The purpose of this study was to delineate the association between endometriosis and pelvic inflammatory disease (PID) and the prevalence of this coexistence. MATERIALS & METHODS: The records of all patients with endometriotic ovarian cysts treated at the 3rd Department of Obstetrics and Gynecology of the University of Athens and in “Lito” Maternity Hospital of Athens from 2000 through 2007 were reviewed. RESULTS: During this 7-year period 720 women underwent surgery due to endometriotic ovarian cysts. The average age was 40.9 years (range: 17-70). Median diameter of the cysts was 4.495 cm and 59% were located in the right ovary. PID was identified in 21 (2.9%) cases. The average age of these women was 31 years (range: 21-39). Half of the women presented with fever (10/21; 47.6%). Ultrasound examination was performed in all women, followed by laparoscopy. In 47.6% (10/21) the PID abscess was located in the right ovary and the rest (52.38%) in the left. The mean diameter of the endometriotic cysts in these women was 3.52 cm. Laparoscopy was the treatment of choice in all the women with the exception of five cases, where due to technical difficulties during laparoscopy, a laparotomy was performed. In all the cases with PID, abscesses were evacuated laparoscopically. No operative complications were observed. CONCLUSIONS: Endometriosis and PID are two conditions that can easily confuse the physician in setting the diagnosis, especially in the situation where they co-exist. In our study we report that the prevalence of PID in women with endometriosis is sufficiently higher than the prevalence in the general population.

Fertil Steril. 2010 Jan 23. [Epub ahead of print]

Polymorphisms in MMP-2 and MMP-9 promoter regions are associated with endometriosis.

Saare M, Lamp M, Kaart T, Karro H, Kadastik U, Metspalu A, Peters M, Salumets A.

Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.

In this case-control study, we investigated the potential associations of MMP-2 and MMP-9 gene promoter region polymorphisms as well as MMP-2 promoter haplotypes with susceptibility to endometriosis in women of caucasian origin. The results demonstrated that polymorphisms in MMP-2 (-735 C/T) and MMP-9 (-1562 C/T) were associated with elevated risk of endometriosis and that certain MMP-2 promoter haplotypes were more common in control group. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Jan 23. [Epub ahead of print]

Laparoendoscopic single-site (LESS) surgery in patients with benign adnexal disease.

Escobar PF, Bedaiwy MA, Fader AN, Falcone T.

Department of OB/Gyn and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio.

OBJECTIVE: To present our initial experience in laparoscopic surgery for benign adnexal disease performed exclusively through an umbilical incision using a single three-channel port and flexible laparoscopic instrumentation. DESIGN: Case report. SETTING: Tertiary-care referral center. PATIENT(S): Since November, 2008, we have performed single-port laparoscopic surgery in nine patients diagnosed with benign adnexal disease. Patients with adnexal masses or endometriosis and a body mass index of <35 kg/m(2) were selected. INTERVENTION(S): Laparoendoscopic single-site (LESS) surgery. In each case, a multichannel port was inserted into the peritoneum through a 1.5-2.0-centimeter umbilical incision. MAIN OUTCOME MEASURES: Feasibility, postoperative pain score, age, BMI, estimated blood loss. RESULT(S): Eight of nine cases were completed successfully, without conversion to a standard laparoscopic approach or to laparotomy. An additional 3 mm extraumbilical port was required in one patient with stage 4 endometriosis. Seven out of nine patients had earlier abdominal surgery. The operative blood loss ranged from minimal to 75 mL. Duration of hospital stay was <24 hours in all cases. Minimal use of postoperative narcotics was required, and no intraoperative complications occurred. CONCLUSION(S): The LESS surgery for benign adnexal disease is feasible in patients with or without earlier surgery. Additional investigation is needed to evaluate the safety and long-term outcomes of this new approach. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Jan 22. [Epub ahead of print]

Endometrial stromal progesterone receptor-A/progesterone receptor-B ratio: no difference between women with and without endometriosis.

Gentilini D, Vigano P, Vignali M, Busacca M, Panina-Bordignon P, Caporizzo E, Di Blasio AM.

Molecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy.

The aim of the present study was to investigate whether alterations of the P receptor-A/P receptor-B ratio could be considered an etiopathogenetic factor for endometriosis. We failed to observe statistically significant differences in both P receptor-A/P receptor-B messenger RNA and protein ratio between endometrial stromal cells derived from women with and without endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Reprod Biomed Online. 2009 Dec 16. [Epub ahead of print]

Effect of delaying post-operative conception after conservative surgery for endometriosis.

Somigliana E, Vercellini P, Daguati R, Giambattista E, Benaglia L, Fedele L.

Department of Obstetrics and Gynecology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.

The objective of this study was to determine whether delaying attempts to conceive after surgery for endometriosis impacts on reproductive prognosis. Patients operated on for endometriosis who were not seeking pregnancy at the time of surgery were selected (n=124) from a large survey regarding reproductive outcome of women with the disease. Pregnancy rate and rate of second surgery were compared between women who attempted conception within 12 months after surgery (n=61) and those compared who postponed attempts for 12 months or more (n=63). In women delaying attempted conception, the adjusted incidence rate ratio for pregnancy and repetitive surgery was 0.79 (95% CI 0.46-1.35) and 1.70 (95% CI 0.86-3.38), respectively. In conclusion, attempting conception shortly after surgery appears advisable since delaying is associated with a lower pregnancy rate and a higher rate of recurrence. However, these differences did not reach statistical significance and this advice is thus not mandatory. Larger studies are warranted to validate these conclusions. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Eur J Obstet Gynecol Reprod Biol. 2010 Jan 20. [Epub ahead of print]

Determinant factors of fertility outcomes after laparoscopic colorectal resection for endometriosis.

Daraï E, Carbonnel M, Dubernard G, Lavoué V, Coutant C, Bazot M, Ballester M.

Service de Gynécologie-Obstétrique, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, 4 rue de la Chine, 75020 Paris, France.

OBJECTIVE: The aims of this prospective study were to evaluate fertility, pregnancy outcomes and their determinant factors after laparoscopic segmental colorectal resection for endometriosis. STUDY DESIGN: We studied 83 women who underwent colorectal resection for endometriosis. Thirty-nine women (47%) had an associated infertility and 51 (61.4%) wished to conceive after surgery. Surgical route was exclusive laparoscopy in 77 cases (92.7%) and laparoconversion in 6 (7.3%). RESULTS: Twenty-nine pregnancies were obtained in 24 patients (43.6%) including 20 spontaneous (69%) and 9 by IVF (31%). The median time to conceive spontaneously was 6 months and 20 months by IVF. Among the 39 infertile women, 18 (46%) conceived during the study period. A relation was found between pregnancy rate and patient age (p=0.02). Reduction in pregnancy rate was correlated to the presence of adenomyosis (p=0.04) and high ASRM total score (p<0.001) as well as exclusive laparoscopy compared to conversion to laparotomy for colorectal resection (p=0.01). CONCLUSION: Adenomyosis and conversion to laparotomy as well as patient age, ASRM score appeared determinant factors of fertility outcome. Copyright © 2010. Published by Elsevier Ireland Ltd.

AJR Am J Roentgenol. 2010 Feb;194(2):355-61.

MRI of endometriotic cysts in association with ovarian carcinoma.

Tanaka YO, Okada S, Yagi T, Satoh T, Oki A, Tsunoda H, Yoshikawa H.

Department of Radiology, University of Tsukuba, Ibaraki, Japan. ytanaka@md.tsukuba.ac.jp

OBJECTIVE: Although mural nodules are considered to be the most important hallmark in the recognition of ovarian cancers accompanied with endometriotic cysts, benign neoplasms and even inflammatory diseases can show similar MRI findings. We sought to clarify the MRI characteristics of malignancy accompanied with endometriotic cysts of the ovary. MATERIALS AND METHODS: Contrast-enhanced MRI was performed and endometriosis was pathologically confirmed in 49 patients with endometriotic cysts displaying mural nodules. Malignancy was pathologically diagnosed in 33 patients and benignity, in 16. Clinical data including patient age and MRI findings in terms of the size of the endometriotic cysts, number of loculi, presence of shading of the cysts, size of the mural nodules, signal intensity of the mural nodules on T1- and T2-weighted images, and contrast enhancement of the mural nodules were retrospectively reviewed. Statistical analysis of each parameter used the Mann-Whitney U test. RESULTS: The mean age of the patients and mean size of the endometriotic cysts were significantly higher in patients with a malignant condition than in those with a benign condition. Contrast enhancement of the mural nodules was observed in 97% of malignant and 44% of benign tumors. The size of the mural nodules was significantly larger in patients with a malignant condition than in those with a benign condition. Differences in size between the bilateral diseases, multilocularity, existence of shading, and the signal intensities of mural nodules were not significantly different between the malignant and benign conditions. CONCLUSION: Endometriotic cysts with enhanced mural nodules are not always complicated with malignancy. In elderly patients, the presence of large enhanced nodules on large endometriotic cysts is more likely to indicate malignancy.

Eur J Obstet Gynecol Reprod Biol. 2010 Jan 19. [Epub ahead of print]

Effect of human seminal fluid on the growth of endometrial cells of women with endometriosis.

Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H.

Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

OBJECTIVES: We investigated the effect of human seminal fluid on the growth of endometrial cells derived from women with and without endometriosis. STUDY DESIGN: Seminal plasma (SP) was collected from 18 healthy fertile men. Serum, peritoneal fluid (PF) and tissue specimens of eutopic and ectopic endometrium were collected from 45 women with endometriosis and 20 women without endometriosis during laparoscopic surgery. Prostaglandin (PG) E2, hepatocyte growth factor (HGF), and estradiol (E2) levels in each sample of SP, serum and PF were measured by enzyme-linked immunosorbent assay. The growth pattern of cells derived from eutopic and ectopic endometria in response to SP was examined by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. RESULTS: Seminal plasma was able to significantly stimulate the growth of epithelial cells and stromal cells derived from the eutopic and ectopic endometria of women with endometriosis (2-3-fold) when compared with control media. The SP-promoted proliferation of both gland cells and stromal cells derived from eutopic endometria was also remarkably higher in women with endometriosis than that of women without endometriosis. Although levels of PGE2, HGF and E2 in SP were variable when compared with other body fluids, the levels of PGE2 and HGF in SP were significantly higher than those in either peritoneal fluid or serum of women with or without endometriosis. Pretreatment of cells with individual anti-PGE2 antibody, anti-HGF antibody and two selective estrogen receptor modulators, tamoxifen and raloxifene was unable to suppress SP-mediated growth of endometrial cells. However, pretreatment of cells with combined anti-PGE2 antibody plus anti-HGF antibody or combined anti-PGE2 antibody plus anti-HGF antibody plus tamoxifen or raloxifene was able to significantly suppress SP-promoted growth of eutopic and ectopic endometrial cells. CONCLUSION: Human seminal fluid enriched with different macromolecules may promote the growth of endometrial cells derived from women with endometriosis. Our findings may suggest some detrimental effect of unprotected sexual intercourse in women with endometriosis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Curr Med Res Opin. 2010 Mar;26(3):729-36.

Add-back therapy use and its impact on LA persistence in patients with endometriosis.

Fuldeore MJ, Marx SE, Chwalisz K, Smeeding JE, Brook RA.

Abbott Laboratories, Abbott Park, IL, USA.

Abstract Objectives: Persistence and compliance in women with endometriosis who are receiving gonadotropin-releasing hormone agonists (GnRH-a) may be limited by its hypoestrogenic side effects. Use of concomitant therapy with norethindrone acetate (NA), estrogen, estrogen/progestin combinations, or other progestin (i.e., ‘add-back therapy’ [ABT]) is recommended to alleviate these side effects. This retrospective study evaluated ABT utilization and its effect on compliance and persistence in patients with endometriosis taking the GnRH-a leuprolide acetate (LA) depot suspension. Methods: A retrospective analysis of a large pharmacy claims database identified patients who started LA therapy from 2002 to 2004 for the treatment of endometriosis. Patients were identified as having received ABT if they started 7 days before, or within 45 days of the last LA fill. Results: A total of 1285 women with endometriosis who began using LA were identified with 12 months of evaluable data: 211 (16.4%) used concomitant NA therapy, 116 (9.0%) used concomitant estrogen-based therapy, 28 (2.2%) used concomitant combination estrogen- and progestin-based therapies, 56 (4.4%) used concomitant progestin-based therapy, and 874 (68.0%) did not use any ABT. Mean (+/-SD) LA persistence in women receiving NA-based ABT was 5.83 +/- 2.98 months, compared with 4.25 +/- 2.62 months for those not using ABT (P < 0.0001). Average medication possession ratio was 0.43 +/- 0.20 for women receiving NA-based ABT versus 0.32 +/- 0.18 for those not receiving any ABT (P < 0.0001). Patients < 30 years of age were most likely to continue therapy longer and have greater compliance compared with the older age group cohorts (P < 0.01). Patients who used ABT continued to do so for 3.79 +/- 3.21 months. Limitations: Limitations of this study include those associated with the use of retrospective claims databases: It does not include any information regarding the patient’s pain symptoms, disease severity, or other factors, which could correlate to compliance and persistence. Conclusions: Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.

Cochrane Database Syst Rev. 2010 Jan 20;(1):CD001398.

Laparoscopic surgery for subfertility associated with endometriosis.

Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninckx PR, Olive D.

Department of Obstetrics and Gynaecology, South Auckland Clinical School, Middlemore Hospital, Private Bag 93311, Auckland, New Zealand.

Update of:

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation, often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by the division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (June 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009), and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies were eligible for inclusion within the review. Both studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses, and complications of surgery. MAIN RESULTS: When combining live birth rate and ongoing pregnancy after 20 weeks, meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only. The odds ratio (OR) was 1.64 (95% confidence interval (Cl) 1.05 to 2.57) in favour of laparoscopic surgery. Meta-analysis also demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only in terms of clinical pregnancy rates, with an OR of 1.66 (95% Cl 1.09 to 2.51) favouring laparoscopic surgery. The results still need to be interpreted with caution as Marcoux 1997 reported a large positive effect of surgery whereas Gruppo Italiano reported a small negative effect. When considering fetal losses, meta-analysis did not demonstrate an effect of laparoscopic surgery when compared to diagnostic laparoscopy only. The OR was 1.33 (95% Cl 0.60 to 2.94) favouring diagnostic laparoscopy only. AUTHORS’ CONCLUSIONS: The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility.

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