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Int J Womens Health. 2013 Sep 30;5:613-7.

Offering extended use of the combined contraceptive pill: a survey of specialist family planning services.

Sauer U1Mann SBrima NStephenson J.

 

Abstract

BACKGROUND:

The purpose of this study was to determine attitudes to, and provision of, extended regimens for taking the combined oral contraceptive pill (COC) by specialist contraception practitioners from three contrasting specialist contraception services in London.

METHODS:

An online cross-sectional survey was administered to all doctors and nurses, who counsel, provide, or prescribe the oral contraceptive pill at each clinic.

RESULTS:

A total of 105 clinicians received the questionnaire and 67 (64%) responded. Only one of three clinics initiated and maintained guidelines for extended COC use. In that service, 60% of staff prescribing COC advised more than 50% of patients regarding alternative COC regimens. In the other two services, this was discussed with 20% and 6% of patients, respectively (P < 0.001). The reasons for prescribing extended use included cyclic headaches, menorrhagia, patient request, menstrual-related cramps, and endometriosis, and did not differ between the three different settings. The most common extended regimens were 63 pills or continuous use until bleeding occurs, followed by a hormone-free interval. Concerns highlighted by providers and patients were “unhealthy not to have a monthly bleed”, “future fertility”, and “breakthrough bleeding”. Such comments highlight the need for further information for providers and patients.

CONCLUSION:

There is growing evidence, backed by national guidance, about extended COC use, but routine provision of this information is patchy and varies ten-fold, even within specialist family planning services. Targeted training, use of service guidelines, and implementation research will be needed to extend patient choice of different COC regimens and change clinical practice.

 

 

Fertil Steril. 2014 Jan;101(1):183-190.e4.

An overview of the current status of clinical trials on endometriosis: issues and concerns.

Guo SW1.

 

Abstract

OBJECTIVE:

To examine and compare differences, if any, between industry- and nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect of prior published positive preclinical results, or lack thereof, on trial status.

DESIGN:

Cross-sectional study of clinical trials on endometriosis that evaluate drugs/biologicals registered at ClinicalTrials.gov as of July 3, 2013.

SETTING:

University-affiliated hospital.

PATIENT(S):

None.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Trial status, size, phase, and duration; use of comparator groups; drug classes, number of arms, targeting conditions; and presence or absence of prior positive preclinical results before the launch of the trial.

RESULT(S):

Eighty trials were identified. The trials sponsored by industry and non-industry have distinct features, differing in trial status, phase, comparator, drug classes, number of arms, trial size, and duration. The phase II/III trials are predominantly industry supported, but these trials frequently use placebo as the comparator. Trials launched without prior published preclinical results do not seem to fare well, although the presence of such studies is no guarantee for success.

CONCLUSION(S):

Questions as to whether the drug on trial is truly superior to the best available drug or of its cost-benefit profile are overlooked in most cases. There seems to be a deluge of “me-too” drugs with equivocal superiority over existing drugs and cost-benefit profiles. Because clinical trials are time-consuming, no blockbuster drug for endometriosis seems to be on the horizon yet.

 

 

Int J Gynaecol Obstet. 2013 Dec;123 Suppl 2:S4-8.

The changing prevalence of infertility.

Petraglia F1Serour GIChapron C.

 

Abstract

Infertility is a major, multifaceted issue worldwide whose prevalence is increasing in both high- and low-income countries. The reasons are numerous, and may differ among world regions, but lifestyle and nutritional factors, epidemic infections, and sexually transmitted diseases are major determinants in most latitudes. Three other reasons may explain the increasing incidence of infertility. First, owing to the widespread use of contraception, the choice of delaying the first pregnancy until the third decade of life places men and women at higher risk for sexually transmitted diseases, and women at higher risk for uterine fibroids, endometriosis, polycystic ovary syndrome, and chronic anovulation. Second, prolonged exposure to chronic stress and environmental pollutants may play a critical role in decreasing fertility. Third, gonadotoxic oncologic treatments allow many patients to survive cancer, at the cost of their fertility. This consideration may justify the development of treatments that preserve fertility.

 

 

Adv Anat Pathol. 2013 Nov;20(6):378-86.

Identifying Lynch syndrome in patients with ovarian carcinoma: the significance of tumor subtype.

Chui MH1Gilks CBCooper KClarke BA.

 

Abstract

Up to 15% of ovarian cancers are etiologically linked with hereditary susceptibility. Within this group, germline mutations in mismatch repair (MMR) genes, known otherwise as Lynch syndrome (LS), account for the majority of cases that are not associated with mutations in BRCA1 or BRCA2. Clinical schemas specific for gynecologic cancers have been developed to identify patients with LS; however, many of the recommendations are poorly defined. Few case series of germline-confirmed LS-associated ovarian cancers have been reported, limited by small sample size and often lacking central pathology review. Much insight has been gained from studies of unselected cohorts, using immunohistochemical assessment of MMR protein expression or microsatellite instability analysis. In spite of contradictory results, likely reflective of differences in study design, sample size and methodology, a recurring observation is the overrepresentation of “endometriosis-associated tumors,” namely, endometrioid and clear cell subtypes, in the group of ovarian tumors with MMR deficiency. In this review, we summarize the clinical and histomorphologic features of LS-associated/MMR-deficient ovarian epithelial cancers and recommend that reflex testing be performed on the basis of tumor subtype.

 

 

Curr Oncol Rep. 2013 Dec;15(6):566-72.

Clear cell carcinoma of ovary and uterus.

Glasspool RM1McNeish IA.

 

Abstract

Clear cell carcinomas of the female genital tract are rare tumours with a fearsome reputation for having poor responses to conventional platinum-based chemotherapy and poor prognosis. However, it is now clear that early-stage ovarian clear cell carcinoma has an excellent prognosis and may not require any adjuvant therapy. In addition, radiotherapy may also have a key role to play in adjuvant management of clear cell tumours. Identification of patients who truly do not need adjuvant chemotherapy is important. The past 3 years has seen a significant improvement in our understanding of clear cell carcinoma biology-in particular, the role of mutations in the chromatin remodelling gene ARID1A as key drivers that are common to clear cell carcinomas of ovarian and endometrial origin. Moreover, gynaecological clear cell carcinomas appear to share many features with renal clear cell tumours, suggesting a common pathogenesis. This raises the possibility of clinical trials that include patients with clear cell tumours from different organs of origin. Dissecting the role of disordered chromatin organisation in clear cell carcinoma pathogenesis is a key priority. Finally, the role of endometriosis and the attendant chronic inflammation are recognised. The inflammatory cytokine interleukin-6 appears to play a key role in clear cell carcinoma biology and is an excellent potential therapeutic target.

 

 

Am J Reprod Immunol. 2013 Dec;70(6):497-508.

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis.

Kim SH1Ihm HJOh YSChae HDKim CHKang BM.

 

Abstract

PROBLEM:

We evaluated whether the expression of NF-кB p65 subunit is increased in the eutopic endometrium and/or in the ovarian endometrioma of women with advanced stage endometriosis, and ascertained in vitro effects of proinflammatory cytokines on the expression and DNA binding of NF-кB p65 subunit in endometrial cells.

METHOD OF STUDY:

Immunohistochemistry was performed to compare the nuclear NF-кB p65 subunit immunoreactivity between women with and without advanced stage endometriosis. The nuclear NF-кB p65 subunit expression and DNA binding were also analyzed in endometrial cells treated with tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β) utilizing Western blot analysis, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay.

RESULTS:

The immunoreactivity of the nuclear NF-кB p65 subunit was significantly increased in the eutopic endometrium as well as in the ovarian endometrioma of women with endometriosis compared with the controls. In vitro treatment of endometrial cells with TNF-α and IL-1β led to a significant increase in nuclear NF-кB p65 subunit expression and DNA binding.

CONCLUSIONS:

The nuclear expression of NF-κB p65 is increased in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis, which strongly suggests that NF-кB signaling plays a crucial role in the pathogenesis and/or pathophysiology of endometriosis.

 

 

J Obstet Gynaecol Res. 2014 Feb;40(2):495-500.

Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease.

Terao M1Koga KFujimoto AWada-Hiraike OOsuga YYano TKozuma S.

 

Abstract

AIM:

The aim of this study was to identify factors that can predict clinical course among patients hospitalized with pelvic inflammatory disease (PID).

METHODS:

Ninety-three patients who needed hospitalization with a diagnosis of PID were retrospectively studied. Patients who were discharged within 7 days by conservative treatment were defined as favorable course cases (n = 44). Patients who needed more than 7 days of hospitalization and/or surgery were defined as poor course cases (n = 49). Twenty variables were evaluated by univariate and logistic regression analysis: age, history of pregnancy/delivery, gynecological open/laparoscopic surgery, PID, oral contraceptives/intrauterine device use and intrauterine operation before onset, body temperature, signs of peritoneal irritation, vomiting/diarrhea, abnormal vaginal discharge, endometriosis/fibroid/adenomyosis/any cystic lesion detected by ultrasonography, white blood cell counts/C-reactive protein (CRP) levels . The cut-off value was calculated by receiver-operator curve (ROC) analysis.

RESULTS:

Factors associated with poor clinical course were advanced age (P < 0.01), history of gynecological open surgery (P < 0.05), any cystic lesion detected by ultrasonography (P < 0.05) and high CRP levels (P < 0.05). High CRP levels and intrauterine operation before onset were independently associated with poor clinical course. The cut-off value for CRP was 4.4 mg/dL.

CONCLUSION:

This study identified variables that can predict poor clinical course of PID. These results can assist gynecologists with identifying patients at risk and optimizing the choice of management.

 

 

Int J Gynaecol Obstet. 2013 Dec;123 Suppl 2:S18-24

Anatomical causes of female infertility and their management.

Abrao MS1Muzii LMarana R.

 

Abstract

The main female anatomical causes of infertility include post-infectious tubal damage, endometriosis, and congenital/acquired uterine anomalies. Congenital (septate uterus) and acquired (myomas and synechiae) diseases of the uterus may lead to infertility, pregnancy loss, and other obstetric complications. Pelvic inflammatory disease represents the most common cause of tubal damage. Surgery still remains an important option for tubal factor infertility, with results in terms of reproductive outcome that compare favorably with those of in vitro fertilization. Endometriosis is a common gynecologic condition affecting women of reproductive age, which can cause pain and infertility. The cause of infertility associated with endometriosis remains elusive, suggesting a multifactorial mechanism involving immunologic, genetic, and environmental factors. Despite the high prevalence of endometriosis, the exact mechanisms of its pathogenesis are unknown. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. In the majority of cases, surgical treatment of endometriosis has promoted significant increases in fertilization rates. There are obvious associations between endometriosis and the immune system, and future strategies to treat endometriosis might be based on immunologic concepts.

 

 

Am J Surg Pathol. 2013 Nov;37(11):1635-47

Endometrioid stromal sarcoma: a clinicopathologic study of 63 cases.

Masand RP1Euscher EDDeavers MTMalpica A.

 

Abstract

Endometrioid stromal sarcoma (also known as extrauterine endometrial stromal sarcoma [EESS]) is an uncommon tumor that occurs in women over a wide age range. The extrauterine location, non-gynecologic symptoms and signs at presentation, and confounding histologic features can pose a diagnostic challenge. In this study, we present the clinicopathologic features of 63 cases of EESS seen during a period of 21 years at our institution. Clinical information and pathology material were reviewed. Ages ranged from 27 to 87 years (median: 50 years). The most common symptoms and signs were an abdominal or pelvic mass, pain, vaginal bleeding, and gastrointestinal symptoms. The tumor size ranged from 1.2 to 24.5 cm. The most common sites of involvement were the ovaries (25), bowel wall (28), abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites were involved in 40 cases. Forty-six of 49 tumors had a classic microscopic appearance, and 3 had dedifferentiation; in 20 cases, there was vascular invasion. Fibroma-like stroma was seen in 30, hyaline plaques in 23, sex cord elements in 11, smooth muscle differentiation in 4, and myxoid change in 4 cases. Endometriosiswas noted in 30 cases. Immunohistochemical results included: CD10 positivity in 31, desmin positivity in 9 (focal), estrogen receptor positivity in 28, and progesterone receptor positivity in 33 cases. In 25% of cases, an initial diagnosis other than EESS was made: sex cord-stromal tumors (4), gastrointestinal stromal tumor (3), leiomyosarcoma (3), liposarcoma (1), müllerian adenosarcoma (1), synovial sarcoma (1), malignant peripheral nerve sheath tumor (1), small round blue cell tumor (1), and atypical stromal endometriosis (1). Primary treatment was cytoreductive surgery for 61 patients and hormonal therapy for 2 patients. Adjuvant treatment included hormonal therapy, chemotherapy, and radiation therapy. Follow-up (5 to 336 months) information was available for 53 patients: alive with no evidence of disease, 29; alive with disease, 15; and dead of disease, 9 (median period of 70 months from diagnosis to death). Thirty-three patients had recurrent disease, and 10 patients were lost to follow-up. EESS is commonly associated with endometriosis and tends to be indolent with a propensity for recurrence. Seven of 9 patients who died of the disease had bowel involvement, and 3 had tumors with dedifferentiation. Besides the latter, no other histologic finding correlated with the clinical behavior of these tumors.

 

Arch Gynecol Obstet. 2014 Jan;289(1):13-21.

Mechanism of pain generation for endometriosis-associated pelvic pain.

Kobayashi HYamada YMorioka SNiiro EShigemitsu AIto F.

Abstract

PURPOSE:

Endometriosis-associated pelvic pain appears due to persistent nociceptive stimulation, but the precise mechanisms remain poorly understood.

METHODS:

A search was conducted to screen and select articles from PubMed.

MAIN RESULTS:

Neurotrophins (NTs), a family of neuronal growth factors, are overexpressed in endometriosisand encompass NGF, BDNF and NT-3 and NT-4/5. NT receptors, TrkA and p75NTR, and NT receptor-interacting proteins, MAGE and NDN, were also expressed. NTs and their receptors play a role in the development and maintenance of neural tissues in non-neuronal cell types such as endometriosis. Nerve fibers contain unmyelinated sensory C, myelinated sensory Adelta and adrenergic nerve fibers that innervate abnormal cell growths. An increased release of proinflammatory cytokines from endometriotic lesions is responsible for the excessive sensory innervation and development of chronic pelvic pain.

CONCLUSIONS:

The preponderance of the inflammatory milieu and subsequent hyperinnervation might be involved in the pathophysiology of pain generation in women with endometriosis.

 

 

PLoS One. 2013 Oct 4;8(10):e76808.

Involvement of the Wnt/β-catenin signaling pathway in the cellular and molecular mechanisms of fibrosis in endometriosis.

Matsuzaki S1Darcha C.

 

Abstract

BACKGROUND:

During the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function. However, the cellular and molecular mechanisms of fibrosis in endometriosis remain to be clarified.

OBJECTIVES:

The objective of the present study was to investigate whether the Wnt/β-catenin signaling pathway was involved in regulating the cellular and molecular mechanisms of fibrosis in endometriosis in vitro and to evaluate whether fibrosis could be prevented by targeting the Wnt/β-catenin pathway in a xenograft model of endometriosis in immunodeficient nude mice.

METHODS:

Seventy patients (40 with and 30 without endometriosis) with normal menstrual cycles were recruited. In vitro effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090) on fibrotic markers (alpha smooth muscle actin, type I collagen, connective tissue growth factor, fibronectin) and collagen gel contraction were evaluated in endometrial and endometriotic stromal cells from patients with endometriosis. In vitro effects of activation of the Wnt/β-catenin signaling pathway by treatment with recombinant Wnt3a on profibrotic responses were evaluated in endometrial stromal cells of patients without endometriosis. The effects of CGP049090 treatment on the fibrosis of endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice.

RESULTS:

Treatment with PKF 115-584 and CGP049090 significantly decreased the expression of alpha smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin mRNAs in both endometriotic and endometrial stromal cells with or without transforming growth factor-β1 stimulation. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels was significantly decreased by treatment with PKF 115-584 and CGP049090 as compared to that of untreated cells. The animal experiments showed that CGP049090 prevented the progression of fibrosis and reversed established fibrosis in endometriosis.

CONCLUSION:

Aberrant activation of the Wnt/β-catenin pathway may be involved in mediating fibrogenesis in endometriosis.

 

 

J Obstet Gynaecol Res. 2014 Feb;40(2):479-84.

Lack of association between LIPC-514 C/T polymorphism of hepatic lipase and endometriosis in Iranian women.

Sahmani M1Ghaleh TDDarabi MDarabi MRashvand ZNajafipour R.

 

Abstract

AIM:

Patients with endometriosis may suffer from dyslipidemia. Hepatic lipase (HL) is involved in the metabolism of lipoproteins and has an important role in reverse cholesterol transport. The aim of this study was to investigate the association between the LIPC-514 C/T polymorphism in the HL gene and the risk of endometriosis in a group of Iranian women.

METHODS:

Ninety-seven patients with endometriosis and 107 women who were negative for endometriosis after diagnostic laparoscopy, as control group, were enrolled in this cross-sectional study. Samples were analyzed for polymorphism of the HL gene using polymerase chain reaction restriction fragment length polymorphism.

RESULTS:

Multivariate analysis was used to examine the association between the risk of endometriosis and LIPC-514 C/T polymorphism. There was no statistically significant difference in the frequency of the LIPC-514 C/T polymorphism between patients and the controls (60.7% CC, 34.6% CT, 4.7% TT versus 68.4%, 27.4%, 4.2%, respectively, P = 0.52).

CONCLUSION:

The present study suggested that the LIPC-514 C/T polymorphism of the HL gene has no significant association with the risk of endometriosis in the studied Iranian women.

 

 

 

J Minim Invasive Gynecol. 2014 Mar-Apr;21(2):203-9.

Effect of surgery for endometrioma on ovarian function.

Shah DK1Mejia RB2Lebovic DI3.

 

Abstract

Endometriosis affects a significant proportion of reproductive-aged women. The impact of the disease on ovarian function is an important consideration when planning treatment in women who want to retain the potential of future childbearing. This review will specifically address the association between endometriomas and diminished ovarian reserve, with a particular focus on the impact of surgical endometrioma resection on ovarian function. The existing literature supports an adverse effect of ovarian endometriomas on spontaneous ovulation rates, markers of ovarian reserve, and response to ovarian stimulation, although data on clinical pregnancy and live birth rates remain inconsistent. Surgical removal of endometriomas may worsen ovarian function by removing healthy ovarian cortex or compromising blood flow to the ovary. It is evident that surgical excision of endometriomas acutely impairs ovarian function as measured by ovarian reserve markers; whether this represents progressive or long term impairment remains the subject of ongoing investigation.

 

 

J Obstet Gynaecol. 2013 Oct;33(7):715-9.

Endovaginal ultrasound-assisted pain mapping in endometriosis and chronic pelvic pain.

Yong PJ1Sutton CSuen MWilliams C.

 

Abstract

The objective of this study was to determine if the combination of tenderness-guided endovaginal ultrasound and digital pelvic exam (i.e. EVUS-assisted exam) for preoperative pain mapping, in cases without nodules or endometriomas, increases sensitivity/specificity for laparoscopic findings. This was a retrospective review of women with chronic pelvic pain ± infertility with preoperative pain mapping exam prior to laparoscopy (n = 97, 2006-7). Predictor variables (EVUS-assisted exam vs digital pelvic exam alone, for pain mapping) were coded as tender vs non-tender. Primary outcome was findings on laparoscopy (e.g. endometriosis or adhesions) and was coded as abnormal vs normal. We found that EVUS-assisted exam had greater sensitivity (0.81, 95% CI: 0.70-0.89) for abnormal laparoscopy compared with digital pelvic exam alone (0.58, 95% CI: 0.46-0.69) (McNemar’s test, p < 0.001). Specificity was limited for both types of pain mapping (0.22, 95% CI: 0.08-0.44 for EVUS-assisted; and 0.39, 95% CI: 0.20-0.61 for digital), with no significant difference (p = 0.13). In conclusion, in the absence of nodules or endometriomas, EVUS-assisted exam increases sensitivity, but with no benefit in specificity, for prediction of abnormal laparoscopy.

 

 

J Obstet Gynaecol. 2013 Oct;33(7):725-8.

Apoptosis through regulation of Bcl-2, Bax and Mcl-1 expressions in endometriotic cyst lesions and the endometrium of women with moderate to severe endometriosis.

Korkmaz D1Bastu EDural OYasa CYavuz EBuyru F.

 

Abstract

The aim of the study was to evaluate apoptosis through regulation of Bcl-2, Bax and Mcl-1 proteins by comparing their expressions in endometriotic cyst lesions and the endometrium of the patients with moderate to severe endometriosis. This is a cross-sectional study of 30 women in reproductive age with a clinical or sonographic suspicion of endometrioma, who underwent laparoscopy. Bcl-2 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly reduced in the cystic endometriotic lesions (p < 0.0001). There was a significant difference in Bcl-2 expression between cystic endometriotic stromal cells and endometrial stromal cells (p < 0.0001). Bax expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the endometrium (p < 0.0001). There was a significant difference in Bax expression between cystic endometriotic stromal cells and endometrial stromal cells (p = 0.03). Mcl-1 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the cystic endometriotic lesions (p = 0.003). Apoptosis may play a role in the pathophysiology of endometriosis by potentially contributing to the survival of regurgitating endometrial cells in the peritoneal cavity.

 

 

Hum Reprod Update. 2014 Mar-Apr;20(2):217-30.

The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary.

Sanchez AM1Viganò PSomigliana EPanina-Bordignon PVercellini PCandiani M.

 

Abstract

BACKGROUND:

Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology. We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue.

METHODS:

Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components.

RESULTS:

An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be significantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst.

CONCLUSIONS:

There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size.

 

 

Wideochir Inne Tech Maloinwazyjne. 2013 Sep;8(3):187-91.

Endoureterotomy is not a sufficient treatment for intrinsic ureteral endometriosis.

Guo T1Gu CFeng CDing QXu CLi B.

 

Abstract

AIM:

To investigate whether intrinsic ureteral endometriosis could be managed by laser endoureterotomy.

MATERIAL AND METHODS:

We studied retrospectively 6 patients with intrinsic ureteral endometriosis who underwent laser endoureterotomy and reviewed their clinical data. Pathological sections of them have also been studied by immunohistochemistry for expressional levels of oestrogen (ER) and progesterone (PR) receptors. Ten sections of normal endometrium were included as a control.

RESULTS:

Five patients had recurrence of ureteral stricture within 6 months postoperatively despite hormonal therapy for 3 to 6 months. One patient had recurrence 8 months after endoureterotomy. Two patients had secondary surgery for ureteroureterostomy and pathology confirmed recurrence of endometriosis. Immunohistochemistry revealed decreased ER and PR expression compared to the control.

CONCLUSIONS:

Endoureterotomy with hormonal therapy may not be suitable for ureteral endometriosis due to inadequate cutting and expressional change of ER and PR.

 

 

 

 

Int J Clin Exp Pathol. 2013 Sep 15;6(10):2011-20.

IL-22 in the endometriotic milieu promotes the proliferation of endometrial stromal cells via stimulating the secretion of CCL2 and IL-8.

Guo Y1Chen YLiu LBChang KKLi HLi MQShao J.

 

Abstract

Interleukin-22 (IL-22) is a member of the IL-10 cytokine family and plays critical roles in inflammation, immune surveillance, and tissue homeostasis. However, whether IL-22 regulates the growth of endometrial stromal cells (ESCs), and participates in the pathogenesis of endometriosis remain unclear. In this study, we found that the expression of IL-22 and it receptors (IL-22R1 and IL-10R2) in eutopic endometrium and ectopic lesion of women with endometriosis was higher than that from healthy control. Recombinant human IL-22 (rhIL-22) stimulated the proliferation of ESCs in a dosage-dependent manner. On the contrary, anti-human IL-22 neutralizing antibody inhibited the proliferation of ESCs in vitro. The stimulatory effect of IL-22 on the proliferation of ESCs could be reversed by inhibitor of STAT5, ERK1/2 or AKT signal pathway. However, blocking STAT3, JNK or P38 signal pathway had no these effects. By Enzyme-linked immunosorbent assay (ELISA) and flow cytometry assay, we demonstrated the rhIL-22 not only stimulate the secretion of CCL2 and IL-8, but also significantly up-regulate the expression of IL-8 receptor CXCR1 on ESCs. Meanwhile, STAT5, ERK1/2 and or AKT signal inhibitors could abrogate the increase of CCL2, IL-8 and CXCR1 levels induced by rhIL-22. However, rhIL-22 had not similar influence on CCL2 receptor CCR2. Our current results suggested that the higher level of IL-22 and it receptors in eutopic endometrium may stimulate the expression of CCL2, IL-8/CXCR1, and further promote the growth of ESCs possibly through activating STAT5, MAPK/ERK1/2 and or AKT signal pathways, which may be involved in the occurrence and development of endometriosis.

 

 

Int J Clin Exp Pathol. 2013 Sep 15;6(10):2030-8.

NME1 suppression of endometrial stromal cells promotes angiogenesis in the endometriotic milieu via stimulating the secretion of IL-8 and VEGF.

Chang KK1Liu LBJin LPMeng YHShao JWang YMei JLi MQLi DJ.

 

Abstract

Nonmetastatic gene 23-H1 (NME1, also known as nm23-H1) is a wide-spectrum tumor metastasis suppressor gene that plays an important role in suppressing the proliferation, adhesion and invasion of endometrial stromal cells (ESCs). The present study is undertaken to explore the mechanism by which NME1 in ESCs from endometriosis modulates the angiogenesis and herein participates in the pathogenesis of endometriosis. The expression of NME1 in the primary ESCs from normal endometrium without endometriosis was higher than that from eutopic endometrium and ectopic lesion with endometriosis. Silencing NME1 stimulated the secretion of angiogenic factors interleukin-8 (IL-8) and vascular-endothelial growth factor (VEGF) of the eutopic ESCs from women with endometriosis, and these effects could be abrogated by MAPK/ERK1/2 or AKT inhibitor. In addition, the supernatant of NME1-silenced ESCs increased the expression of angiogenesis-relative molecules CD62E and CD105, and promoted angiogenesis of human umbilical vein endothelial cells (HUVECs). Anti-human IL-8 or VEGF neutralizing antibody reversed the effect on angiogenesis of HUVECs induced by NME1-silenced ESCs. Our current results suggest that the abnormal lower expression of NME1 in ESCs secrete more IL-8 and VEGF through activation of MAPK/ERK1/2 and AKT signal pathways, up-regulate the level of CD62E and CD105, and finally lead to numerous angiogenesis of vascular endothelial cells in the endometriotic milieu, which is beneficial to the origin and development of endometriosis.

 

 

Int J Clin Exp Pathol. 2013 Sep 15;6(10):2129-36.

MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro.

Huang F1Cao JLiu QZou YLi HYin T.

 

Abstract

OBJECTIVE:

Now there are more and more evidences that Cyclooxygenase-2 (COX-2) plays an important role in angiogenesis of endometriosis (EMs). Vascular endothelial growth factor (VEGF) has a potent angiogenic activity. However, it is worth studying about the regulating mechanism of COX-2/COX-1 and VEGF in the development of human endometriosis in vitro. The current study was designed to investigate the effect of 4 cytokines on COX-2/COX-1 expression and the effect of IL-1β on VEGF release in human endometriosis stromal cells (ESC), and to explore the related signaling pathways involved in vitro.

METHODS:

Isolation, culture and identification of ESC. Cells were treated with 4 cytokines, and the inhibitor mitogen-activated protein-Erk (MEK) and the inhibitor p38 mitogen-activated protein kinase (MAPK) prior to adding cytokine IL-1β. COX-2 protein expression was measured by western blot and VEGF secretion was determined by ELISA.

RESULTS:

Among four kinds of cytokines, IL-1β treatment increased COX-2 protein expression and VEGF release in three ESC, and TNF-α had the same effect on COX-2 protein level as IL-1β only in ectopic and eutopic ESC, and MCSF had only slight effect on ectopic ESC. In contrast, cytokines had no effect on COX-1 expression. We also demonstrated that MAPK reduced the synthesis of COX-2 by IL-1β induced. COX-2 inhibitor reduced VEGF release by IL-1β induced.

CONCLUSIONS:

  1. i) In human ESC in vitro, IL-1β up-regulated the COX-2 expression through the activation of p38 MAPK pathway, and not to COX-1. ii) Up-regulation of VEGF level by IL-1β treatment was found in human endometriosisstromal cell and COX-2 inhibitor was involved in this process.

 

 

Gynecol Endocrinol. 2014 Jan;30(1):34-7.

A 12-year cohort study on adverse pregnancy outcomes in Eastern Townships of Canada: impact of endometriosis.

Aris A1.

 

Abstract

The aim of this study was to provide a temporal-spatial reference of adverse pregnancy outcomes (APO) and examine whether endometriosis promotes APO in the same population. Among the 31 068 women who had a pregnancy between 1997 and 2008 in Eastern Townships of Canada, 6749 (21.7%) had APO. These APO increased significantly with maternal age and over time (r(2 )= 0.522, p = 0.008); and were dominated by preterm birth (9.3%), pregnancy-induced hypertension (8.3%) including gestational hypertension (6.5%), low birth weight (6.3%), gestational diabetes (3.4%), pregnancy loss (2.2%) including spontaneous abortion (1.5%) and stillbirth (0.6%), intrauterine growth restriction (2.1%) and preeclampsia (1.8%). Among the 31 068 pregnancies, 784 (2.5%) had endometriosis and 183 (23.3%) had both endometriosis and APO. Endometriosis has been shown to increase the incidence of fetal loss (OR = 2.03; 95% CI = 1.42-2.90, p < 0.0001), including spontaneous abortion (OR = 1.89; 95% CI = 1.23-2.93, p = 0.005) and stillbirth (OR = 2.29; 95% CI = 1.24-5.22, p = 0.012). This study provides a temporal-spatial reference on APO, which is a valuable tool for monitoring, comparing and correcting. It is also the first study to highlight an impact of endometriosis on the incidence of spontaneous abortion and stillbirth.

 

 

Metabolism. 2014 Jan;63(1):32-41.

Vitamin D in endometriosis: a causative or confounding factor?

Sayegh L1Fuleihan Gel-HNassar AH.

 

Abstract

OBJECTIVE:

The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis.

DESIGN:

Comprehensive review.

MATERIALS AND METHODS:

Systematic literature search in Medline for relevant publications from 1946 until June 2013.

RESULTS:

Endometriosis risk may be influenced by dietary vitamin D intake and plasma hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing enzymes, 24-hydroxylase and 1-α hydroxylase, are found in the normal cycling endometrium and also in the eutopic and ectopic endometrium of women with endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions through regulation of specific genes and via immunomodulation. The endometrium in endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If vitamin D and its metabolites are implicated in endometriosis-associated infertility, it is likely through interference with HOXA10 gene expression. The Gc2 phenotype of vitamin D binding protein is prevalent in women with endometriosis and may be implicated in its pathogenesis. In a mouse model, Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic lesions and recurrence.

CONCLUSION:

A biological plausibility for a role of vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis and treatment of endometriosis is suggested in this article, but is difficult to illustrate due to sparse evidence from human studies limited primarily to case-control studies. A significant knowledge gap precludes the establishment of a clear cause-effect relationship. The intriguing leads presented herein need to be investigated further with placebo-controlled supplementation trials.

 

 

Aust N Z J Obstet Gynaecol. 2014 Feb;54(1):9-12

Review of lipiodol treatment for infertility – an innovative treatment for endometriosis-related infertility?

Johnson NP1.

 

Abstract

A lipiodol hysterosalpingogram was the routine test for tubal patency as recently as the 1970s. Observational studies, then randomised controlled trials, provided evidence of a fertility enhancing effect of lipiodol. It has been found to improve fertility for women with normal tubal patency, particularly where the woman has a history of endometriosis. Previous successful treatment for infertility with lipiodol is a marker of further successful treatment for infertility in a repeat procedure. Whilst lipiodol is probably effective at flushing debris that could hinder fertility from fallopian tubes, it also exerts immunobiological effects in pelvic peritoneum and on the endometrium that could be responsible for fertility enhancement. Effects of lipiodol on the endometrium that might be important at the time of the implantation window are a reduced expression of osteopontin and an increased number of uterine natural killer cells postlipiodol. The effect of lipiodol uterine bathing for women with endometriosis, repeat in vitro fertilisation (IVF) implantation failure and other reproductive disorders merits further investigation. Lipiodol presents a new, simple, low invasive, inexpensive treatment option for endometriosis-related infertility and might have wider applications.

 

 

Hum Reprod Update. 2014 May-Jun;20(3):386-402.

Structural and molecular features of the endomyometrium in endometriosisand adenomyosis.

Benagiano G1Brosens IHabiba M.

 

Abstract

BACKGROUND Adenomyosis and endometriosis were initially described as ‘adenomyoma’. When the retrograde menstruation theory became widely accepted to explain the pathogenesis of endometriosis, since it does not explain adenomyosis, the two conditions came to be seen as distinct entities. However, emerging evidence suggests that both diseases may be linked to changes in the inner portion of the myometrium. In addition, similar anomalies were found in the eutopic endometrium of the two conditions and the debate has re-opened. A common origin for both adenomyosis and endometriosis would have relevance not only for understanding uterine function and pathophysiology, but also for clinical management and treatment. METHODS The Scopus and Medline databases were searched for all original articles published in English up to the end of 2012. Search terms included ‘adenomyosis’; ‘endometriosis’; ‘endometrium’; ‘eutopic endometrium’; ‘inner myometrium’; ‘junctional zone’. Special attention was paid to articles comparing features of eutopic endometrium in the two conditions. RESULTS A number of similarities exist between adenomyosis and endometriosis and, by using magnetic resonance and laparoscopy, it was found that, at least in some subgroups, the two conditions often coexist. In both situations the inner myometrium (or junctional zone) is altered, although alterations are much more marked in adenomyosis where a thickness >12 mm is today considered sufficient for diagnosis. Research has shown differences between the eutopic endometrium of women with both diseases when compared with controls. There is an immune dysfunction and there are alterations of adhesion molecules, cell proliferation and apoptosis. An increase in cytokines and inflammatory mediators has also been observed. Finally, the presence of oxidative stress and anomalies in free-radical metabolism may alter uterine receptivity. When the two conditions were compared, dissimilarities were also observed in the extent of apoptosis inhibition and in the expression of some inflammatory mediators. It is not clear if observed differences are primarily related to presenting symptoms. Finally, both conditions are steroid dependent and research suggests a role for epigenetic mechanisms. The analysis indicates that much of the published research may have been influenced by the method of diagnosis and/or has not been controlled for the presenting symptoms, the concomitant presence of both diseases or full consideration of fluctuations within cycle phase. CONCLUSIONS It is difficult to draw firm conclusions from existing evidence since major diagnostic limitations still exist and there is a systematic bias in clinical presentation. In addition, scanty information is available on the natural history of endometriosis and no studies exist on the natural history of adenomyosis. Notwithstanding these limitations, a number of similarities, but also some differences have been found between the eutopic endometrium in the two diseases. These findings need to be taken with considerable caution as the few instances where the research was repeated yielded conflicting results.

 

 

Med Mol Morphol. 2014 Dec;47(4):189-95.

Effect of a dienogest for an experimental three-dimensional endometrial culture model for endometriosis.

Prechapanich J1Kajihara TFujita KSato KUchino STanaka KMatsumoto SAkita MNagashima MBrosens JJIshihara O.

 

Abstract

The pathogenesis of endometriosis remains poorly understood at least in part because early stages of the disease process are difficult to investigate. Previous studies have proposed a three-dimensional fibrin matrix culture model to study human endometriosis. We examined the ultrastructural features of the endometriosis in this model and assessed the effect of a progestin on endometrial outgrowth and apoptosis in this culture system. Endometrial explants were placed in three-dimensional fibrin matrix culture and treated with and without various concentrations of the progestin dienogest. By the second week, endometrial gland-like formation was established in outgrowths both attached to and at a distance from the explants. These cells formed a combination of clumps and tubular monolayers surrounding a central cavity. Electron microscopy demonstrated that these cells are polarized with microvilli on the apical surface, desmosome-like structures, and basement membrane; features consistent with glandular epithelial cells. Outgrowth of endometrial stromal cells and glandular formation was impaired in response to dienogest in a dose-dependent manner. Our study shows that the human endometrial explants cultured in three-dimensional fibrin matrix establish outgrowths that ultrastructurally resemble ectopic endometrial implants. This model may provide insight into the cellular processes leading to endometriosisformation and enables screening of therapeutic compounds.

 

 

Bull Exp Biol Med. 2013 Aug;155(4):512-7.

Immunocytochemical analysis of proliferative activity of endometrial and myometrial cell populations in focal and stromal adenomyosis.

Nepomnyashchikh LM1Lushnikova ELMolodykh OPPichigina AK.

 

Abstract

Immunocytochemical study has shown that Ki-67 antigen is detected in adenomyosis in both endometrial and myometrial cell populations (in the eutopic and ectopic endometrial glandular epithelium, stromal cells, smooth muscle cells, and vascular endotheliocytes of the endometrium and myometrium), the label index differing significantly in different cell populations. The highest labeled cell index is found in the endometrial gland epitheliocytes in focal adenomyosis (23.2 ± 2.9%); in the stromal variant this index is by 2.8 times lower despite the fact that this variant is associated with endometrial glandular hyperplasia in the majority of cases. Proliferative activity of secretory epitheliocytes is significantly lower in both adenomyosis variants than in the normal eutopic endometrium. Stromal adenomyosis is characterized by 2-fold higher proliferative activity of the cytogenic stroma than that in focal adenomyosis.

 

 

Rev Med Inst Mex Seguro Soc. 2013 Sep-Oct;51(5):522-31.

Relationship among anthropometric and gluco-metabolic parameters, bone mineral density and endometriosis.

Nava-González EJ1de la Garza-Casas YESalazar-Montalvo RGGallegos-Cabriales EC.

 

Abstract

in EnglishSpanish

BACKGROUND:

women with endometriosis may have a decreased bone mineral density (BMD). Several studies have shown that accumulation of adipose tissue profoundly affects BMD. It has also been documented that excess body fat is associated with risk of developing endometriosis. The aim was to analyze the relationship between BMD, fat mass, and the insulin-glucose axis in women with endometriosis.

METHODS:

thirty women with a diagnosis of endometriosis established by surgery were enrolled to participate in an observational prospective study. Anthropometry was performed to determine body mass index, and a dual X-ray densitometry to collect data on body composition and BMD. Glucose and insulin determinations were performed. Women were divided in two groups: with normal weight (n = 18) or overweight (n = 12). For the analysis of the results, we used descriptive statistics and Pearson’s test.

RESULTS:

normal weight/overweight: mean age 32.5/35.2 years; body mass index 21.5/30.2; adiposity index: 27.7 %/36.1 %; fat mass index: 35.4/45.8 %; overweight women showed a significant value with p < 0.05.

CONCLUSIONS:

overweight, high values of adiposity index and fat mass index were related to endometriosis. This could support the hypothesis about a common pathogenesis among endometriosis, osteoporosis, diabetes and obesity.

 

 

Maturitas. 2013 Nov;76(3):284-9.

Stem cells and the reproductive system: historical perspective and future directions.

Duke CM1Taylor HS.

 

Abstract

Recent findings in stem cell biology have presented new perspectives and opportunities for the treatment of reproductive disease. In a departure from the long held dogma of embryologically fixed numbers of oocytes, current literature suggests that human ovaries contain stem cells which form new oocytes even in adulthood and that these stem cells can be cultured in vitro to develop into mature oocytes. These findings have provided new hope and broader options for fertility preservation. Evidence of endometrial regeneration by bone marrow stem cells in endometrial tissue of women who received bone marrow transplant highlight potential for the novel treatments of uterine disorders and supports new theories for the etiology of endometriosis – ectopic transdifferentiation of stem cells. Further, endometrial derived stem cells have been demonstrated to be useful in the treatment of several chronic and often debilitating diseases, including Parkinson’s Disease and Diabetes. Other cells that may present future therapeutic benefits for a myriad of disease states include placental and fetal cells which enter maternal circulation during pregnancy and can later promote parenchymal regeneration in maternal tissue. These findings highlight novel functions of the uterus and ovaries. They demonstrate that the uterus is a dynamic organ permeable to fetal stem cells capable of transdifferentiation as well as a renewable source of multipotent stem cells. While we still have much to understand about stem cells, their potential applications in reproductive biology and medicine are countless.

 

 

Saudi Med J. 2013 Oct;34(10):1035-42.

Rectus abdominis endometriosis. A descriptive analysis of 10 cases concerning this rare occurrence.

Mostafa HA1Saad JHNadeem ZAlharbi F.

 

Abstract

OBJECTIVE:

To report 10 cases of rectus abdominis endometrioma, emphasizing the clinical presentations, imaging investigations, cytohistological findings, and surgical treatment employed.

METHODS:

This is a descriptive analysis of 10 surgically-proven cases of rectus abdominis muscle endometriosis, seen over a 5-year period from 2007 to 2012 at Sohag University Hospital, Sohag, Egypt and Najran Armed Forces Hospital, Najran, Saudi Arabia. All patients had undergone ultrasonography. Computerized tomography (CT) and magnetic resonance imaging (MRI) were performed in some cases. Surgical excision was the way of treatment in all patients.

RESULTS:

This study was carried out in 10 women with a mean age of 33.9 years. Nine cases had previous history of cesarean section (CS) while one patient had laparoscopy converted to laparotomy for ovarian cyst. All patients were presented with abdominal pain but only 3 had a palpable mass. Ten lesions within the rectus abdominis muscle were detected with automated ultrasound and MRI depicted one lesion, which was missed by ultrasound in a patient who had 2 concomitant lesions. Preoperative fine needle aspiration (FNA) was carried out in 2 patients. Wide surgical excision was performed in all cases. Histopathology was confirmatory in each instance. No complications or recurrence were recorded on follow-up (6-24 months; mean 13.2 months).

CONCLUSION:

This disease is not as rare as previously thought, and should be included in the differential diagnosis of abdominal wall masses in reproductive-age females.

 

 

J Obstet Gynaecol Res. 2014 Feb;40(2):473-8.

What is the success of ultrasonography of benign adnexal masses?

Bayoğlu Tekin Y1Dede FS.

 

Abstract

AIM:

To assess the diagnostic accuracy of the ultrasonographic discrimination of benign adnexal masses.

METHODS:

This was a prospective study, evaluating 245 consecutive cases using real-time gray-scale ultrasonography in a tertiary education hospital.

RESULTS:

Diagnostic accuracy was high for simple cysts and solid masses as κ-values of 0.824 and 0.816 and accuracy was moderate for endometriomas, dermoid cysts and cystadenomas as κ-values of 0.758, 0.689 and 0.627, respectively, and low for hemorrhagic cysts as a κ-value of 0.587. A logistic regression model was developed using ultrasonographic characteristics of the adnexal masses. Irregularity at lining of the inner wall, presence of solid component, papillary projections and echogenicity were shown to have a strong impact on the diagnosis of benign masses.

CONCLUSION:

Although ultrasonography is a useful technique for the diagnosis of benign adnexal masses, it is limited in diagnostic accuracy. Pattern recognition is the most favored method for ultrasonographic diagnosis. Logistic regression analysis can contribute to diagnostic accuracy.

 

 

J Obstet Gynaecol Res. 2014 Feb;40(2):485-94.

Clinical profiles of 710 premenopausal women with adenomyosis who underwent hysterectomy.

Li X1Liu XGuo SW.

 

Abstract

AIM:

The aim of this study was to determine the frequency of various symptoms and their associated characteristics in women with adenomyosis who underwent hysterectomy, and to determine which symptoms are likely to go with which others in these patients.

MATERIAL AND METHODS:

In 2007, 1697 consecutive patients underwent hysterectomy in our hospital. Among them, 734 (43.3%) were histologically confirmed to have adenomyosis, and 710 of them were premenopausal. The medical charts of all 734 patients were retrieved, and their demographic, clinical information and postoperative findings were recorded. We used the Verbal Descriptor Scale to measure the preoperative severity of dysmenorrhea. The Apriori Algorithm was used for mining the association of different symptoms.

RESULTS:

Among the 710 premenopausal patients, only 4.5% of them had no symptoms. Dysmenorrhea was the most common complaint, occurring in 81.7% of patients. Dysmenorrhea co-occurred most frequently with menorrhagia. The presence of adhesion, presence of endometriosis, complaint of menorrhagia, longer duration of disease, gravidity, palpable pain during pelvic examination, and diffuse adenomyosis were positively associated with the severity of dysmenorrhea. Age, severity of dysmenorrhea, and complaint of metrorrhagia were positively associated with the risk of menorrhagia.

CONCLUSIONS:

Dysmenorrhea is the most common complaint in women with adenomyosis, which often goes with that of menorrhagia. Adenomyosis often co-occurs with endometriosis and leiomyomas. Various factors are associated with the risk of having different symptoms.

 

 

Reprod Biol Endocrinol. 2013 Oct 22;11:101.

Efficacy of sperm motility after processing and incubation to predict pregnancy after intrauterine insemination in normospermic individuals.

de Araújo LF1de Araújo Filho EFácio CLBossoni MCMachado-Paula LACorrente JECavagna MMatheus PCPontes A.

 

Abstract

BACKGROUND:

Intrauterine insemination (IUI) is widely used to treat infertility, and its adequate indication is important to obtain good pregnancy rates. To assess which couples could benefit from IUI, this study aimed to evaluate whether sperm motility using a discontinuous gradient of different densities and incubation in CO2 in normospermic individuals is able to predict pregnancy.

METHODS:

A total of 175 couples underwent 175 IUI cycles. The inclusion criteria for women were as follows: 35 years old or younger (age range: from 27 to 35 years) with normal fallopian tubes; endometriosis grades I-II; unexplained infertility; nonhyperandrogenic ovulatory dysfunction. Men with normal seminal parameters were also included. All patients underwent ovarian stimulation with clomiphene citrate and human hMG or r-FSH. When one or (at most) three follicles measuring 18 to 20 mm were observed, hCG (5000 UI) or r-hCG (250 mcg) was administered and IUI performed 36-40 h after hCG. Sperm processing was performed using a discontinuous concentration gradient. A 20 microliters aliquot was incubated for 24 h at 37 degrees C in 5% CO2 following a total progressive motility analysis. The Mann-Whitney and Chi-square tests, as well as a ROC curve were used to determine the cutoff value for motility.

RESULTS:

Of the 175 couples, 52 (in 52 IUI cycles) achieved clinical pregnancies (CP rate per cycle: 29.7%). The analysis of age, duration and causes of infertility did not indicate any statistical significance between pregnancy and no pregnancy groups, similar to the results for total sperm count and morphology analyses, excluding progressive motility (p < 0.0001). The comparison of progressive motility after processing and 24 h after incubation between these two groups indicated that progressive motility 24 h after incubation was higher in the pregnancy group. The analysis of the progressive motility of the pregnancy group after processing and 24 h after incubation has not shown any motility difference at 24 h after incubation; additionally, in couples who did not obtain pregnancy, there was a statistically significant decrease in progressive motility 24 h after incubation (p < 0.0001). The ROC curve analysis generated a cutoff value of 56.5% for progressive motility at 24 h after incubation and this cutoff value produced 96.1% sensitivity, 92.7% specificity, 84.7% positive predictive value and 98.3% negative predictive value.

CONCLUSIONS:

We concluded that the sperm motility of normospermic individuals 24 h after incubation at 37 degrees C in 5% CO2, with a cutoff value of 56.5%, is predictive of IUI success.

 

 

Arch Gynecol Obstet. 2014 Apr;289(4):823-30.

Effect of lesion location on endometriotic adhesion and angiogenesis in SCID mice.

Lu Z1Zhang WJiang SZou JLi Y.

 

Abstract

OBJECTIVE:

To evaluate the effects of lesion location on adhesion and angiogenesis of transplanted endometriotic lesions in SCID mice.

METHODS:

Three groups of female SCID mice included intraperitoneal (i.p.) (n = 12), subcutaneous (s.c.) (n = 12), and mock surgery (control) (n = 12). At 2 weeks after ovariectomy, the mice were transplanted with eutopic endometrium from endometriosis patients either subcutaneously or sutured within the peritoneal, or underwent mock surgery. After 4 weeks, the mice were sacrificed to evaluate the adhesion and volume changes of the implanted lesions. Furthermore, semiquantitative immunohistochemical staining was performed to analyze expression of MMP-2 and TIMP-2 as adhesion makers, and vWF, VEGF, and HIF-1α as angiogenesis markers.

RESULTS:

Adhesion occurred in 9 of 12 mice in the i.p. group, 3 of 12 mice in the s.c. group, and 3 of 12 mice in the control group. Fisher’s exact test showed that the difference of adhesion occurrence between i.p. and s.c. groups was statistically significant (p < 0.05). Graft volume changes were higher in the s.c. group than those in the i.p. group. MMP-2 expression was higher in the s.c. group than that in the i.p. group (p < 0.01). There was no significant difference of TIMP-2 expression between s.c. and i.p. groups. vWF, VEGF, and HIF-1α expression was significantly higher in the s.c. group than that in the i.p. group (p < 0.01).

CONCLUSIONS:

Lesion location might be involved in the pathological changes of endometriosis. The intraperitoneal location is related to endometriotic adhesion, whereas the subcutaneous location is related to the infiltration of endometriotic lesions.

 

Hum Reprod. 2014 Feb;29(2):324-36.

Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study.

Govatati S1Kodati VLDeenadayal MChakravarty BShivaji SBhanoori M.

 

Abstract

STUDY QUESTION:

Are mutations in the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene associated with endometriosis?

SUMMARY ANSWER:

Loss of heterozygosity (LOH) at the 10q23.3 locus, PTEN somatic mutations and changes in the levels and distribution of proteins in the PTEN-PI3K/Akt signal transduction pathway are associated with endometriosis.

WHAT IS KNOWN ALREADY:

Endometriosis has a strong genetic basis. Recent genome-wide association and linkage studies have reported a significant association of endometriosis with 7p15.2, 9p21 and 10q23-26 loci. PTEN, which maps to 10q23.3, acts as a tumor suppressor gene through the action of its phosphatase protein product, phosphatase and tensin homolog (PTEN). This phosphatase is involved in the regulation of the cell cycle, and mutations of PTEN are a step in the development of many cancers.

STUDY DESIGN, SIZE, DURATION:

A total of 1252 subjects of Indian origin (endometriosis patients = 752; controls = 500) were recruited to participate in this case-control study. Recruitment took place from 2001 to 2009 at Institute of Reproductive Medicine (IRM), Kolkata, India; Infertility Institute and Research Centre (IIRC), Secundrabad, India and Vasavi Medical and Research Centre, Hyderabad, India.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

LOH on 10q, 9p and 7p was analyzed in analogous ectopic-eutopic endometria along with blood samples from 32 advanced stage endometriosis patients by PCR-GeneScan analysis. Genotyping of PTEN was carried out on genomic DNA of analogous ectopic-eutopic endometria (n = 32) as well as blood samples from 720 patients and 500 controls by PCR-sequencing analysis to explore somatic and germ-line mutations, respectively. The levels and distribution of PTEN, p-Akt, p-Bad and p27 were analyzed in the eutopic endometria of patients (n = 5) and controls (n = 5) using western-blot and immunohistochemistry.

MAIN RESULTS AND THE ROLE OF CHANCE:

PCR-GeneScan analysis revealed a higher LOH frequency at 10q23.3 (84.4%) compared with other loci analyzed, hence we focused our attention on PTEN. PCR-sequencing analysis revealed seven novel somatic mutations and 23 germ-line polymorphisms in patients. Among somatic mutations, a frame-shift insertion at 10:89692992-89692993 (in the functionally important N-terminal phosphatase domain of PTEN) occurred in 11 of the 32 ectopic endometria. Western-blot and immunohistochemical analysis revealed decreased PTEN and increased p-Akt and p-Bad levels in eutopic endometria of patients compared with controls (all comparisons, P < 0.0001). Furthermore, PTEN loss was more frequent in the nucleus than in the cytoplasm. Expression of p27 did not differ between patients and controls.

LIMITATIONS, REASONS FOR CAUTION:

Protein analysis was performed in eutopic endometrial samples from only a small number of patients and controls. In future investigations, a larger sample size should be used and the role of the other genes involved in the PTEN-PI3K/Akt signal transduction pathway should be analyzed.

WIDER IMPLICATIONS OF THE FINDINGS:

Our findings revealed a possible involvement of the PTEN-PI3K/Akt-Bad axis in the pathogenesis of endometriosis, which may facilitate the discovery of suitable pathway inhibitors for disease treatment.

 

 

 

 

J Pathol. 2014 Feb;232(3):330-43

miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis.

Hsu CY1Hsieh THTsai CFTsai HPChen HSChang YChuang HYLee JNHsu YLTsai EM.

 

Abstract

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3′ untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

 

 

Clin Radiol. 2014 Feb;69(2):130-6.

Diffusion-weighted imaging in the evaluation of hormonal cyclic changes in abdominal wall endometriomas.

Genç B1Solak A2Sahin N2Genç M3Oğul H4Sivrikoz ON5Kantarcı M4.

 

Abstract

AIM:

To investigate the utility of diffusion-weighted (DW) magnetic resonance imaging (MRI) in the diagnosis of abdominal wall endometrioma (AWE) and to compare the ADC (apparent diffusion coefficient) values of AWE with those of the uterine endometrium during two different phases of the menstrual cycle.

MATERIALS AND METHODS:

A total of 22 women aged between 27 and 42 years (mean 32.8 years) and who had regular menstrual cycles were included in the study. These patients had a total of 25 AWE lesions. The mean and standard deviation of the ADC values of the normal endometrium/AWE were calculated for the menstrual and luteal phases. All examinations were performed using a 1.5 T magnet (b-values of 50, 400, and 800 mm/s(2)). The results were analysed using the Shapiro-Wilk test, the Pearson correlation test, the analysis of variance (ANOVA) test, and the paired sample t-test.

RESULTS:

The ADC values of the endometrium were different in the two phases of the menstrual cycle (menstrual phase: 0.924 ± 0.171; luteal phase: 1.171 ± 0.135). Similarly, the ADC values of the AWE were different in these phases (menstrual phase: 0.937 ± 0.256, luteal phase: 1.256 ± 0.215). In both AWE and the uterine endometrium, the ADC measurements were significantly lower in the menstrual phase than during the luteal phase. This difference was statistically significant (p < 0.05). There was no significant difference in the ADC values between the endometrial layer and AWE during the same phase (p = 0.216 for menstrual phase, p = 0.104 for luteal phase, paired sample t-test).

CONCLUSION:

The present study demonstrated that in all patients, the DWI features of AWEs were significantly similar to those of the uterine endometrial tissue. Additionally, the ADC measurements of the patients showed similar cyclical changes. These results suggest that the ADC values of a lesion close to the uterine endometrium may be used to differentiate AWE from the other disease entities of the abdominal wall.

 

 

J Minim Invasive Gynecol. 2014 May-Jun;21(3):328-34.

Postoperative medical therapy after surgical treatment of endometriosis: from adjuvant therapy to tertiary prevention.

Somigliana E1Vercellini P2Vigano P3Benaglia L4Busnelli A2Fedele L2.

 

Abstract

The high rate of disease recurrence after surgery is critical and frustrating for women with endometriosis. Adjuvant treatments using a 3- to 6-months course of hormone therapy after surgery have been extensively investigated during the last 2 decades; however, results have been unsatisfactory, primarily because the benefits of hormone therapy rapidly vanish once treatment is discontinued. The protective effect is limited to the period of use. Accordingly, it is recognized that suppressive hormone therapy after surgery markedly prevents recurrent episodes only if given over the long term. The emerging view is that estroprogestins do not ameliorate the effects of surgery but demonstrate tertiary prevention of the disease. They prevent ovulation and reduce retrograde menstrual flow, two crucial events in the pathogenesis of endometriosis. The available literature strongly supports the benefits of prolonged administration of estroprogestins after surgery in preventing recurrence of endometriomas and dysmenorrhea. In contrast, data on dyspareunia and nonmenstrual pelvic pain remain scanty and unconvincing, and there is no information about recurrence of other forms of endometriosis such as peritoneal implants and adhesions. Overall, estroprogestin therapy after surgery to treat endometriosis should be recommended in women who do not seek to become pregnant. Further evidence is warranted to better delineate the beneficial effects of this emerging but convincing strategy.

 

 

 

 

Case Rep Oncol. 2013 Sep 21;6(3):480-4.

Malignant Transformation from Endometriosis to Atypical Endometriosis and Finally to Endometrioid Adenocarcinoma within 10 Years.

Tanase Y1Furukawa NKobayashi HMatsumoto T.

 

Abstract

Atypical endometriosis is reported to possess a precancerous potential attributed to premalignant changes characterized by cytological atypia and architecture proliferation. Moreover, the coexistence of atypical endometriosis and neoplasms had been reported. However, cases of atypical endometriosis transformation to carcinoma are rarely reported. We describe the case of a 33-year-old woman who had a long therapeutic history of endometriosis. Three laparoscopic surgeries were performed to treat endometriosis. After the third surgery, she was diagnosed as having grade 1 endometrioid adenocarcinoma. The histological review of the previous surgery confirmed the diagnosis of atypical endometriosis based on the second specimen. The patient’s disease progressed from a benign endometriotic cyst to atypical endometriosis and finally to endometrioid adenocarcinoma within 10 years. When we encounter cases of atypical endometriosis, it is necessary to consider the possibility of ovarian cancer and carefully follow the patients for long periods.

 

 

BMC Womens Health. 2013 Oct 29;13:43.

Ultrasound mapping of pelvic endometriosis: does the location and number of lesions affect the diagnostic accuracy? A multicentre diagnostic accuracy study.

Holland TK1Cutner ASaridogan EMavrelos DPateman KJurkovic D.

 

Abstract

BACKGROUND:

Endometriosis is a common condition which causes pain and reduced fertility. Treatment can be difficult, especially for severe disease, and an accurate preoperative assessment would greatly help in the managment of these patients. The objective of this study is to assess the accuracy of pre-operative transvaginal ultrasound scanning (TVS) in identifying the specific features of pelvic endometriosis and pelvic adhesions in comparison with laparoscopy.

METHODS:

Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. They all underwent a systematic transvaginal ultrasound examination in order to identify discrete endometriotic lesions and pelvic adhesions. The accuracy of ultrasound diagnosis was determined by comparing pre-operative ultrasound to laparoscopy findings.

RESULTS:

198 women who underwent preoperative TVS and laparoscopy were included in the final analysis. At laparoscopy 126/198 (63.6%) women had evidence of pelvic endometriosis. 28/126 (22.8%) of them had endometriosis in a single location whilst the remaining 98/126 (77.2%) had endometriosis in two or more locations. Positive likelihood ratios (LR+) for the ultrasound diagnosis of ovarian endometriomas, moderate or severe ovarian adhesions, pouch of Douglas adhesions, and bladder deeply infiltrating endometriosis (DIE), recto-sigmoid colon DIE, rectovaginal DIE, uterovesical fold DIE and uterosacral ligament DIE were >10, whilst for pelvic side wall DIE and any ovarian adhesions the + LH was 8.421 and 9.81 respectively.The negative likelihood ratio (LR-) was: <0.1 for bladder DIE; 0.1-0.2 for ovarian endometriomas, moderate or severe ovarian adhesions, and pouch of Douglas adhesions; 0.5-1 for rectovaginal, uterovesical fold, pelvic side wall and uterosacral ligament DIE. The accuracy of TVS for the diagnosis of both total number of endometriotic lesions and DIE lesions significantly improved with increasing total number of lesions.

CONCLUSIONS:

Our study has shown that the TVS diagnosis of endometriotic lesion is very specific and false positive results are rare. Negative findings are less reliable and women with significant symptoms may still benefit from further investigation even if TVS findings are normal. The accuracy of ultrasound diagnosis is significantly affected by the location and number of endometriotic lesions.

 

 

J Sex Med. 2014 Jan;11(1):140-5.

Sexual function in patients with deep infiltrating endometriosis.

Evangelista A1Dantas TZendron CSoares TVaz GOliveira MA.

 

Abstract

INTRODUCTION:

Endometriosis is a benign condition that causes pain and infertility. Sexual dysfunction, particularly deep dyspareunia, is common in patients with endometriosis and interferes with quality of life and conjugal satisfaction.

AIM:

The study aims to assess sexual function in women with deep infiltrating endometriosis.

METHOD:

Fifty-seven women diagnosed with deep infiltrating endometriosis were recruited from Hospital Universitário Pedro Ernesto (HUPE) between July and December 2011. The control group comprised 38 healthy women recruited at the HUPE family planning clinic.

MAIN OUTCOME MEASURES:

The main outcomes are full-scale and individual domain scores on the Female Sexual Function Index (FSFI), a validated questionnaire for functional assessment of sexual function in women.

RESULTS:

Patients with endometriosis had more pain in intercourse than controls, which correlates with lower scores in the FSFI pain domain. However, there were no statistically significant between-group differences in overall (full-scale) FSFI scores.

CONCLUSION:

Women with endometriosis exhibit significant dysfunction in the pain domain of the FSFI questionnaire, but this finding was not sufficient to affect the overall sexual function.

 

 

Hum Reprod. 2014 Feb;29(2):315-23.

Follicular fluid from infertile women with mild endometriosis may compromise the meiotic spindles of bovine metaphase II oocytes.

Da Broi MG1Malvezzi HPaz CCFerriani RANavarro PA.

 

Abstract

STUDY QUESTION:

What is the potential impact of follicular fluid (FF) from infertile women with mild endometriosis (ME) on oocyte quality, especially on nuclear maturation and the meiotic spindle?

SUMMARY ANSWER:

FF from infertile women with ME may compromise nuclear maturation and the meiotic spindles of in vitro matured bovine oocytes.

WHAT IS KNOWN ALREADY:

Controversial studies have suggested that impaired oocyte quality may be involved in the pathogenesis of endometriosis-related infertility. Moreover, some studies have demonstrated alterations in the composition of FF from infertile women with endometriosis. However, to date no study has evaluated the effect of FF from infertile women with ME on the genesis of meiotic oocyte anomalies.

STUDY DESIGN, SIZE, DURATION:

We performed an experimental study. Samples of FF were obtained from February 2009 to February 2011 from 22 infertile women, 11 with ME and 11 with tubal or male factors of infertility (control group), who underwent ovarian stimulation for ICSI at our university IVF Unit. From March 2011 to February 2012 we performed in vitro maturation (IVM) experiments using immature bovine oocytes as described below.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

FF free of blood and containing a mature oocyte was obtained from 22 infertile women during oocyte retrieval for ICSI. Immature bovine oocytes underwent IVM in the absence of FF (No-FF) and in the presence of four concentrations (1, 5, 10 and 15%) of FF from infertile women without endometriosis (C-FF) and with ME (ME-FF). Eleven replicates were performed, each one using FF from a control patient and a patient with ME. Each FF sample was used in only one experiment. After 22-24 h of IVM, oocytes were denuded, fixed and immunostained for morphological visualization of microtubules and chromatin by confocal microscopy.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 1324 cumulus-oocyte complexes were matured in vitro. Of these, 1128 were fixed and 1048 were analyzed by confocal microscopy. The percentage of meiotically normal oocytes was significantly higher for oocytes that underwent IVM in the absence of FF (No-FF; 76.5%) and in the presence of 1% (80.9%), 5% (76.6%), 10% (75%) and 15% (76.2%) C-FF than in oocytes that underwent IVM in the presence of 1% (44.4%), 5% (36.7%), 10% (45.5%) and 15% (51.2%) ME-FF (P < 0.01). No differences were observed among FF concentrations within each group. When the four concentrations from each group were pooled, the number of oocytes in metaphase I stage was significantly higher in the ME-FF (50 oocytes) than in the C-FF (29 oocytes) group and the percentage of meiotic abnormalities was significantly higher when oocytes were matured with ME-FF (55.8%) than with C-FF (23.1%), P < 0.01.

LIMITATIONS, REASONS FOR CAUTION:

Owing to the strict selection criteria for FF donors, this study had a small sample size (11 cases and 11 controls), and thus further investigations using a large cohort of patients are needed to confirm these results. In addition, data obtained from studies using animal models may not necessarily be extrapolated to humans and studies evaluating in vivo matured oocytes from infertile women with ME are important to confirm our results.

WIDER IMPLICATIONS OF THE FINDINGS:

Our results open new insights into the pathogenic mechanisms of infertility related to mild endometriosis, suggesting that FF from infertile women with mild endometriosis may be involved in the worsening of oocyte quality of these women.

 

 

J Gynecol Oncol. 2013 Oct;24(4):376-81.

The roles of ARID1A in gynecologic cancer.

Mao TL1Shih IeM.

 

Abstract

One of the exciting findings in recent cancer genome studies is the discovery of somatic mutations in several chromatin remodeling genes. These studies not only illuminate the emerging roles of chromatin remodeling in the pathogenesis of human cancer but also provide molecular genetic basis of aberrant epigenomic regulation as one of the key mechanisms driving cancer development. This is because chromatin remodeling influences a variety of DNA activities such as replication, transcription, repair, methylation, and recombination. Among the mutated chromatin remodeling genes reported, ARID1A is frequently mutated in a variety of human cancers, especially in endometrium-related neoplasms including ovarian clear cell carcinoma, ovarian endometrioid carcinomas, and uterine endometrioid carcinomas, all of which arise from endometrial epithelium. This review will summarize the recent advances in studying the roles of ARID1A mutations in gynecologic cancers with special emphasis on how this new knowledge will further extend our understanding of the pathogenesis of endometrium-related carcinomas.

 

 

Health Promot J Austr. 2013 Aug;24(2):151-4.

Communicating endometriosis with young women to decrease diagnosis time.

Shadbolt NA1Parker MAOrthia LA.

 

Abstract

ISSUES ADDRESSED:

Endometriosis is estimated to affect approximately 10% of women. Although early detection may enhance health outcomes and fertility, there is a recognised diagnostic delay of 6.7 years. There are limited data on ways to discuss endometriosis with young women. The aims of the present study were to determine what young women know about endometriosis, what young women want to know about endometriosisand how this is best communicated to promote early detection.

METHODS:

Women aged 16-25 years were invited to complete an online survey that was advertised via Facebook, email, Twitter and flyers at high schools and a university.

RESULTS:

In all, 131 women responded to the survey. Fifty-two percent of participants had heard of endometriosis, 89% thought teenagers should be educated about endometriosis and 78% thought that young men should also be educated about the condition. Favoured sources for obtaining information were schools (40%), the Internet (22%) and magazines (13%). Participants were most comfortable talking to a doctor (75%), parent (59%) or friend (51%). Participants primarily wanted to know about the disease, its symptoms, risk factors and treatment. Many participants’ descriptions of endometriosis were vague or inaccurate.

CONCLUSIONS:

The results of the present study indicate that young women are keen to learn about endometriosis, particularly its symptoms. Preferential sources of information appear to be schools or the Internet, and young women appear more comfortable talking to doctors. SO WHAT? To promote early detection of endometriosis, health promotion activities should direct their information towards sources that young women prefer.

 

 

 

 

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