Endocrinology. 2014 May;155(5):1921-30.

Activated AKT pathway promotes establishment of endometriosis.

Kim TH1Yu YLuo LLydon JPJeong JWKim JJ.

 

Abstract

The pathogenesis of endometriosis remains unclear, and relatively little is known about the mechanisms that promote establishment and survival of the disease. Previously, we demonstrated that v-akt murine thymoma viral oncogene homolog (AKT) activity was increased in endometriosis tissues and cells from ovarian endometriomas and that this increase promoted cell survival as well as decreased levels of progesterone receptor. The objective of this study was to demonstrate a role for AKT in the establishment of ectopic lesions. First, a dose-dependent inhibition of AKT in stromal cells from human ovarian endometriomas (OSIS) as well as endometrial stromal cells from disease-free patients (ESC) with the allosteric AKT inhibitor MK-2206 was demonstrated by decreased levels of phosphorylated (p)(Ser473)-AKT. Levels of the AKT target protein, p(Ser256)-forkhead box O1 were increased in OSIS cells, which decreased with MK-2206 treatment, whereas levels of p(Ser9)-glycogen synthase kinase 3β did not change in response to MK-2206. Although MK-2206 decreased viability of both OSIS and ESC in a dose-dependent manner, proliferation of OSIS cells was differentially decreased significantly compared with ESC. Next, the role of hyperactive AKT in the establishment of ectopic lesions was studied using the bigenic, PR(cre/+)Pten(f/+) heterozygous mouse. Autologous implantation of uterine tissues was performed in these mice. After 4 weeks, an average of 4 ± 0.33 lesions per Pten(f/+) mouse and 7.5 ± 0.43 lesions in the PR(cre/+)Pten(f/+) mouse were found. Histological examination of the lesions showed endometrial tissue-like morphology, which was similar in both the Pten(f/+) and PR(cre/+)Pten(f/+) mice. Treatment of mice with MK-2206 resulted in a significantly decreased number of lesions established. Immunohistochemical staining of ectopic lesions revealed decreased p(Ser473)-AKT and the proliferation marker Ki67 from MK-2206-treated mice compared with vehicle-treated mice. Furthermore, levels of FOXO1 and progesterone receptor increased in lesions of mice receiving MK-2206. These results demonstrate that heightened AKT activity plays an active role in the establishment of ectopic endometrial tissues.

 

 

Hum Reprod. 2014 May;29(5):978-88.

MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors.

Braza-Boïls A1Marí-Alexandre JGilabert JSánchez-Izquierdo DEspaña FEstellés AGilabert-Estellés J.

Abstract

STUDY QUESTION:

Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions?

SUMMARY ANSWER:

This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient and their correlation with the most important angiogenic and fibrinolytic factors. WHAT IS ALREADY KNOWN?: An important role for dysregulated miRNA expression in the pathogenesis of endometriosis is well documented. However, to the best of our knowledge, there are no reports of the relationship between angiogenic and fibrinolytic factors and miRNAs when endometrial tissue and different types of endometriotic lesions from the same patient are compared.

STUDY DESIGN, SIZE, DURATION:

Case-control study that involved 51 women with endometriosis and 32 women without the disease (controls).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The miRNA expression profiles were determined using the GeneChip miRNA 2.0 Affymetrix array platform, and the results were analysed using Partek Genomic Suite software. To validate the obtained results, 12 miRNAs differentially expressed were quantified by using miRCURY LNA™ Universal RT microRNA PCR. Levels of vascular endothelial growth factor (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) proteins were quantified by ELISA.

MAIN RESULTS AND THE ROLE OF CHANCE:

Patient endometrial tissue showed significantly lower levels of miR-202-3p, miR-424-5p, miR-449b-3p and miR-556-3p, and higher levels of VEGF-A and uPA than healthy (control) endometrium. However, tissue affected by ovarian endometrioma showed significantly lower expression of miR-449b-3p than endometrium from both controls and patients, and higher levels of PAI-1 and the angiogenic inhibitor TSP-1. A significant inverse correlation between miR-424-5p and VEGF-A protein levels was observed in patient endometrium, and an inverse correlation between miR-449b-3p and TSP-1 protein levels was observed in ovarian endometrioma. Peritoneal implants had significantly higher levels of VEGF-A than ovarian endometrioma samples.

LIMITATIONS, REASONS FOR CAUTION:

Functional studies are needed to confirm the specific targets of the miRNAs differently expressed.

WIDER IMPLICATIONS OF THE FINDINGS:

Differences in miRNA levels could modulate the expression of VEGF-A and TSP-1, which may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in eutopic endometrium from patients might facilitate the implantation of endometrial cells at ectopic sites.

 

Surg Endosc. 2014 Aug;28(8):2474-9.

Robot-assisted laparoscopy for deep infiltrating endometriosis: international multicentric retrospective study.

Collinet P1Leguevaque PNeme RMCela VBarton-Smith PHébert THanssens SNishi HNisolle M.

Abstract

BACKGROUND:

This study aimed to assess the interest in robot-assisted laparoscopy for deep infiltrating endometriosis and to investigate the perioperative results.

METHODS:

From November 2008 to April 2012, 164 women with stage 4 endometriosis who underwent robot-assisted laparoscopy (da Vinci Intuitive Surgical System) were included by to eight international participating clinical centers. This study evaluated the procedures performed, the duration of the intervention, the complications, the recurrence, and the impact on fertility.

RESULTS:

The average operative time was 180 min. The main complications were laparotomy (n = 1, 0.6%), sutured bowel injury (n = 2, 1.2%), transfusion for a 2,300-ml bleed (n = 1), prolonged urinary catheterization (n = 1, 0.6%), ureter-bladder anastomotic leak (n = 1, 0.6%), and ureteral fistula after ureterolysis (n = 2, 1.2%). The reoperation rate was 1.8% (n = 3). The mean follow-up period was 10.2 months. A full recovery was experienced by 86.7% (98/113) of the patients. After surgery, 41.2% (42/102) of the patients had a desire for pregnancy, and 28.2% (11/39) of them became pregnant.

CONCLUSION:

This study analyzed the largest series of robot-assisted laparoscopies for deep infiltrating endometriosis published in the literature. No increase in surgical time, blood loss, or intra- or postoperative complications was observed. The interest in robot-assisted laparoscopy for deep infiltrating endometriosisseems to be promising.

 

 

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by research grants from ISCIII-FEDER (PI11/0091, Red RIC RD12/0042/0029), Consellería de Educación-Generalitat Valenciana (PROMETEO/2011/027), Beca de Investigación Fundación Dexeus para la Salud de la Mujer (2011/0469), and by Fundación Investigación Hospital La Fe (2011/211). A.B-B. has a Contrato Posdoctoral de Perfeccionamiento Sara Borrell-ISCIII (CD13/00005). J.M-A. has a predoctoral grant PFIS-ISCIII (FI12/00012). The authors have no conflicts of interest to declare.

 

Cochrane Database Syst Rev. 2014 Mar 10;(3):CD009590.

Endometriosis: an overview of Cochrane Reviews.

Brown J1Farquhar C.

Abstract

BACKGROUND:

This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis.

OBJECTIVES:

The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis.

METHODS:

Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in ‘Additional tables’.

MAIN RESULTS:

Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There was moderate quality evidence that the levonorgestrel-releasing intrauterine system (LNG-IUD) was more effective than expectant management, and very low quality evidence that danazol was more effective than placebo. There was no consistent evidence of a difference in effectiveness between oral contraceptives and goserelin, estrogen plus progestogen and placebo, or progestogens and placebo, though in all cases the relevant evidence was of low or very low quality. Non-steroidal anti-inflammatory drugs (NSAIDS)A review of NSAIDs reported inconclusive evidence of a benefit in symptom relief compared with placebo. Surgical interventions There were two reviews of surgical interventions. One reported moderate quality evidence of a benefit in pain relief following laparoscopic surgery compared to diagnostic laparoscopy only. The other reported very low quality evidence that recurrence rates of endometriomata were lower after excisional surgery than after ablative surgery. Post-surgical medical interventions Two reviews reported on post-surgical medical interventions. Neither found evidence of an effect on pain outcomes, though in both cases the evidence was of low or very low quality. Alternative medicine There were two systematic reviews of alternative medicine. One reported evidence of a benefit from auricular acupuncture compared to Chinese herbal medicine, and the other reported no evidence of a difference between Chinese herbal medicine and danazol. In both cases the evidence was of low or very low quality. Anti-TNF-α drugs One review found no evidence of a difference in effectiveness between anti-TNF-α drugs and placebo. However, the evidence was of low quality. Reviews reporting fertility outcomes (8 reviews) Medical interventions Four reviews reported on medical interventions for improving fertility in women with endometriosis. One compared three months of GnRH agonists with a control in women undergoing assisted reproduction and found very low quality evidence of an increase in clinical pregnancies in the treatment group. There was no evidence of a difference in effectiveness between the interventions in the other three reviews, which compared GnRH agonists versus antagonists, ovulation suppression versus placebo or no treatment, and pre-surgical medical therapy versus surgery alone. In all cases the evidence was of low or very low quality. Surgical interventions Three reviews reported on surgical interventions. There was moderate quality evidence that both live births or ongoing pregnancy rates and clinical pregnancy rates were higher after laparoscopic surgery than after diagnostic laparoscopy alone. There was low quality evidence of no difference in effectiveness between surgery and expectant management for endometrioma. One review found low quality evidence that excisional surgery resulted in higher clinical pregnancy rates than drainage or ablation of endometriomata. Post-surgical interventions Two reviews reported on post-surgical medical interventions. They found no evidence of an effect on clinical pregnancy rates. The evidence was of low or very low quality. Alternative medicine A review of Chinese herbal medicine in comparison with gestrinone found no evidence of a difference between the groups in clinical pregnancy rates. However, the evidence was of low quality. Adverse events Reviews of GnRH analogues and of danazol reported that the interventions were associated with higher rates of adverse effects than placebo; and depot progestagens were associated with higher rates of adverse events than other treatments. Chinese herbal medicine was associated with fewer side effects than gestrinone or danazol.Three reviews reported miscarriage as an outcome. No difference was found between surgical and diagnostic laparoscopy, between GnRH agonists and antagonists, or between aspiration of endometrioma and expectant management. However, in all cases the quality of the evidence was of low quality.

AUTHORS’ CONCLUSIONS:

For women with pain and endometriosis, suppression of menstrual cycles with gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD) and danazol were beneficial interventions. Laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain. The evidence on NSAIDs was inconclusive. There was no evidence of benefit with post-surgical medical treatment.In women with endometriosis undergoing assisted reproduction, three months of treatment with GnRH agonist improved pregnancy rates. Excisional surgery improved spontaneous pregnancy rates in the nine to 12 months after surgery compared to ablative surgery. Laparoscopic surgery improved live birth and pregnancy rates compared to diagnostic laparoscopy alone. There was no evidence that medical treatment improved clinical pregnancy rates.Evidence on harms was scanty, but GnRH analogues, danazol and depot progestagens were associated with higher rates than other interventions.

 

 

Gynecol Surg. 2014;11:3-7.

Transvaginal endoscopy and small ovarian endometriomas: unravelling the missing link?

Gordts S1Puttemans P1Gordts S1Valkenburg M1Brosens I1Campo R1.

 

Abstract

The incidence of endometriosis in the infertile female is estimated to be between 20 and 50 %. Although the causal relationship between endometriosis and infertility has not been proven, it is generally accepted that the disease impairs reproductive outcome. Indirect imaging techniques and transvaginal laparoscopy now offer the possibility of an early stage diagnosis. Although it remains debated whether the disease is progressive, treatment in an early stage is recommendable as it carries less risk for ovarian damage, hence premature ovarian failure. Under water, inspection with the technique of transvaginal hydrolaparoscopy (THL) accurately shows the invagination of the ovarian cortex as minimal superficial lesions but with the presence of well-differentiated endometrial like tissue at the base, the lateral walls and especially the inner edges of the small endometrioma. An inflammatory environment is responsible for the formation of connecting adhesions with the broad ligament and lateral wall with invasion of endometrial-like tissue and formation of adenomyotic lesions. In around 50 % of the small endometriomas, adhesiolysis is necessary at the site of invagination with opening of the cyst, to free the chocolate content and hereby recognize the underlying endometrioma. The detailed inspection of these early-stage endometriotic lesions at THL reunites the hypothesis of Sampson with the observation of Hughesdon.

J Obstet Gynaecol Res. 2014 Apr;40(4):1132-6.

Endometriosis-associated tumor at the inguinal site: report of a case diagnosed during pregnancy and literature review.

Bergamini A1Almirante GTaccagni GMangili GViganò PCandiani M.

 

Abstract

Malignant degeneration of endometriosis in the inguinal region is rare, and has only been reported in six cases in the literature, none of which was detected during pregnancy. We present the first case of endometriosis-associated adenocarcinoma in the inguinal region in a 34-year-old woman who was 35 weeks’ pregnant. The tumor rapidly grew in the last 2 months of pregnancy as a left inguinal painful mass. Histologically, the tumor consisted of a moderate-to-poorly differentiated ovarian-type endometrioid adenocarcinoma arisen in endometriosis foci of both typical and atypical type. Elective labor induction was performed at 35 weeks of gestation and subsequently the patient underwent a conservative surgical treatment followed by chemotherapy. This case raises issues on the management of such an unusual tumor both during and outside pregnancy.

 

 

J Obstet Gynaecol Can. 2014 Mar;36(3):248-252.

Does laparoscopy safely improve technicity for complex hysterectomy cases?

Grant-Orser A1El Sugy R2Singh SS3.

Abstract

in EnglishFrench

OBJECTIVE:

The minimally invasive surgical (MIS) approach to hysterectomy (vaginal or laparoscopic), when compared with laparotomy, results in shorter length of stay, fewer minor and major complications, and quicker return to normal activity. The complexity of the hysterectomy procedure or pathology may affect the success of an MIS approach. This study examined the indications, complications, and outcomes of all hysterectomies performed, irrespective of the severity of pathology or patient habitus, in a Canadian tertiary level gynaecologic surgical referral service.

METHODS:

We performed a retrospective chart review of all hysterectomies performed by a single surgeon between September 2007 and June 2011, noting indications, complications, and outcomes. One-way analysis of variance was used to calculate the influence of various factors across surgery types. Significance was set at P < 0.05 for all tests.

RESULTS:

A total of 305 cases were included; 291 of these (95.4%) were managed through an MIS approach, providing a technicity rate of 95.4%. Mean patient age was 45.5 years, and mean BMI was 28.9. The main indicators for surgery were fibroids (42.0%), pain (38.4%), and heavy menstrual bleeding (37.4%). Eighty-one percent of cases were tertiary referrals. Of the laparoscopic cohort, endometriosis was moderate-severe in 61.2% of patients. Mean length of stay was 1.14 days, mean uterine weight was 277.6 g, and mean estimated blood loss was 179 mL.

CONCLUSION:

This retrospective study of a tertiary level referral gynaecologic service suggests that complex hysterectomy may be effectively and efficiently managed through an MIS approach.

 

 

Fertil Steril. 2014 May;101(5):1353-8.

Increased expression of antimüllerian hormone and its receptor in endometriosis.

Carrarelli P1Rocha AL2Belmonte G3Zupi E1Abrão MS4Arcuri F1Piomboni P1Petraglia F5.

Abstract

OBJECTIVE:

To evaluate antimüllerian hormone (AMH) and AMH receptor II (AMHRII) mRNA and protein expression in endometrium and in ovarian or deep lesions of women with endometriosis.

DESIGN:

Prospective study.

SETTING:

University hospitals in Italy and Brazil.

PATIENTS:

Patients with endometriosis (n = 55) and healthy women (n = 45).

INTERVENTIONS:

Specimens of endometrium obtained by hysteroscopy from patients with endometriosis and from healthy control subjects; specimens of ovarian endometriosis (n = 29) or of deep endometriosis (n = 26) were collected by laparoscopy. Serum samples were collected in some endometriotic patients (n = 23) and healthy control subjects (n = 20).

MAIN OUTCOME MEASURE(S):

AMH and AMHRII mRNA levels were evaluated by quantitative reverse-transcription polymerase chain reaction and protein localization by immunohistochemistry. AMH levels in tissue homogenates and in serum were assessed by ELISA.

RESULT(S):

Endometrium from women with endometriosis showed higher AMH and AMHRII mRNA levels than control women, with no significant differences between proliferative and secretory phases. Specimens collected from ovarian or deep endometriosis showed the highest AMH and AMHRII mRNA expression. Immunolocalization study confirmed the high AMH and AMHRII protein expression in endometriotic lesions. No difference of serum AMH levels between the groups was found.

CONCLUSION(S):

The increased AMH and AMHRII mRNA and protein expression in endometrium and in endometriotic lesions suggests a possible involvement of AMH in endometriosis.

 

 

Orv Hetil. 2014 Mar 16;155(11):420-3.

Transvaginal specimen extraction after laparoscopic bowel resection in deeply infiltrating endometriosis.

Bokor A1Pohl A1Lukovich P2Rigó J Jr1.

 

Abstract

in EnglishHungarian

The authors report a case of a 27-year-old patient who had deeply infiltrating endometriosis involving the rectum, sigmoid colon and the rectovaginal septum, which was removed by laparoscopic surgery. During surgery the affected bowel segment, the deeply infiltrating nodule of the rectovaginal septum and the posterior vaginal wall were resected and the 12 cm long specimen was removed transvaginally. Postoperative bleeding was noted in the first postoperative day, which was treated laparoscopically, as well. This case history confirms data from the literature showing that the natural orifice specimen extraction procedure can widely be applied during operations for deeply infiltrating endometriosis and that laparoscopic anterior resection is a safe and feasible method for the treatment of colorectal deeply infiltratnig endometriosis. Moreover, perioperative complications can be treated by means of laparoscopic surgery.

 

 

Genet Mol Res. 2014 Jan 28;13(1):636-48.

Association among XRCC1, XRCC3, and BLHX gene polymorphisms and chromosome instability in lymphocytes from patients with endometriosis and ovarian cancer.

Monteiro MS1Vilas Boas DB2Gigliotti CB2Salvadori DM3.

 

Abstract

Endometriosis is a complex disease that has both benign and malignant characteristics. It affects 5-10% of women of reproductive age. Studies have demonstrated the existence of common genetic changes in endometriosis and ovarian cancer, suggesting a possible association between these 2 diseases. However, the mechanisms that lead to the development of cancer from endometriosis remain unknown. In this study, we evaluated 3 groups of women: 72 patients with endometriosis, 70 with ovarian cancer, and 70 healthy individuals (controls). Repair (XRCC1 codons 194 and 399, XPD codons 312 and 751, and XRCC3 codon 241)- and metabolism (BLHX codon 443)-related gene polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique; the efficiency of DNA damage repair was analyzed in vitro in lymphocytes exposed to bleomycin. The logistic regression model was used to evaluate key associations. The results showed an increased average of chromosome breakage in bleomycin-treated lymphocytes from patients with endometriosis and ovarian cancer compared with healthy women. We also detected significant association between XRCC1, XRCC3, and BLHX polymorphisms and a high frequency of chromosomal damage. Women with endometriosis or ovarian cancer may have an altered mechanism of DNA repair, and these defects may be related to a higher incidence of ovarian cancer.

 

 

Reprod Sci. 2014 Aug;21(8):966-972.

Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes.

Kobayashi H1Higashiura Y2Koike N2Akasaka J2Uekuri C2Iwai K2Niiro E2Morioka S2Yamada Y2.

 

Abstract

There is now accumulating evidence that endometriosis is a disease associated with an epigenetic disorder. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles. We hypothesize that hypermethylated endometriosis-associated genes may be enriched at imprinted gene loci. We sought to determine whether downregulated genes associated with endometriosissusceptibility are associated with chromosomal location of the known paternally and maternally expressed imprinting genes. Gene information has been gathered from National Center for Biotechnology Information database geneimprint.com. Several researchers have identified specific loci with strong DNA methylation in eutopic endometrium and ectopic lesion with endometriosis. Of the 29 hypermethylated genes in endometriosis, 19 genes were located near 45 known imprinted foci. There may be an association of the genomic location between genes specifically downregulated in endometriosis and epigenetically imprinted genes.

 

 

J Ultrasound. 2014 Jan 9;17(1):41-6.

Diagnosis of emergencies/urgencies in gynecology and during the first trimester of pregnancy.

Zucchini S1Marra E1.

 

Abstract

in EnglishGerman

Several surgical and/or medical emergencies/urgencies may occur in gynecologic patients and in pregnant women during the first trimester. Particularly, ectopic pregnancies, ruptured or hemorrhagic ovarian cysts, ovarian or adnexal torsions, threatened or inevitable miscarriages, phlogistic gynecological disorders, complications involving the uterine fibroids, endometriosis, and spontaneous uterine rupture are possible acute complications. The diagnosis is suspected on the basis of symptoms (acute pelvic and/or abdominal pain, with or without vaginal bleeding or discharge, until acute abdomen with peritonitis), by means physical evaluation (abdominal, pelvic, and bimanual gynecological examinations), by means of transabdominal (TAS) and/or transvaginal (TVS) sonography, and laboratory tests. However, the diagnosis is often not that simple, especially when the symptoms and clinical signs are minimal, and ultrasound (US) examination is not diriment. The differential diagnosis of abdominal/pelvic pain is broad and includes primarily gastrointestinal and urogenital disorders. Generally, TAS should usually be used in conjunction with TVS for evaluation of the female pelvis. If the US examination is not conclusive, CT or MRI, especially in pregnant patients, should be considered.

 

 

Acta Obstet Gynecol Scand. 2014 May;93(5):483-9.

Reproductive prognosis in endometriosis. A national cohort study.

Hjordt Hansen MV1Dalsgaard THartwell DSkovlund CWLidegaard O.

Abstract

OBJECTIVE:

To assess the reproductive long-term prognosis of women with and without endometriosis, to explore changes over time, and to quantify the contribution of artificial reproductive techniques.

DESIGN:

Cohort study.

SETTING:

Denmark 1977-2009.

SAMPLE:

Data retrieved from four national registries. Among 15-49-year-old women during the period 1977-82, 24 667 were diagnosed with endometriosis and 98 668 (1:4) women without endometriosis were age-matched.

METHODS:

To assess long-term reproductive prognosis, all pregnancy outcomes were identified among the women with and without endometriosis until the end of 2009. To explore changes over time, the endometriosiscohorts were followed for 15 years from the years 1980, 1986, 1992 and 1998, with the corresponding control cohorts. All pregnancy outcomes were categorized into naturally or artificially conceived pregnancies.

MAIN OUTCOME MEASURES:

Births, miscarriages, induced abortions, ectopic pregnancies and hydatidiform moles.

RESULTS:

Compared with women without endometriosis, women with endometriosis had a lowered relative risk for childbirth of 0.93 (95% confidence interval 0.92-0.95), for miscarriages the relative risk was 1.2 (95% confidence interval 1.2-1.3), ectopic pregnancies were almost twice as many (relative risk 1.9, 95% confidence interval 1.8-2.1), while frequencies of induced abortions were equivalent. The chances for childbirth increased over time from 0.82 to 0.92 (p < 0.001) with successive cohorts, but this was restricted to pregnancies from assisted reproduction.

CONCLUSION:

Women with endometriosis have slightly fewer children, but this lessened over time due to artificially conceived pregnancies. The risk for miscarriages and ectopic pregnancies was increased compared with women without the disease.

 

 

Hum Reprod. 2014 May;29(5):964-77.

Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis.

Vercellini P1Consonni DDridi DBracco BFrattaruolo MPSomigliana E.

Abstract

STUDY QUESTION:

Is adenomyosis associated with IVF/ICSI outcome in terms of clinical pregnancy rate?

SUMMARY ANSWER:

In a meta-analysis of published data, women with adenomyosis had a 28% reduction in the likelihood of clinical pregnancy at IVF/ICSI compared with women without adenomyosis.

WHAT IS KNOWN ALREADY:

Estimates of the effect of adenomyosis on IVF/ICSI outcome are inconsistent.

STUDY DESIGN, SIZE, DURATION:

A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all the comparative studies published from January 1998 to June 2013 in the English language literature on IVF/ICSI outcome in women with and without adenomyosis. Two authors independently performed the literature screening, scrutinized articles of potential interest, selected relevant studies and extracted data. Studies were categorized based on research design.

PARTICIPANTS, SETTING, METHODS:

Of the 17 articles assessed in detail, 9 were finally selected based on diagnosis of adenomyosis at magnetic resonance imaging or transvaginal ultrasonography. The quality of studies was evaluated by means of the Newcastle-Ottawa scale. A total of 1865 women were enrolled in the 9 selected studies, 665 of whom in 4 prospective observational studies, and 1200 in 5 retrospective studies. The dichotomous data for clinical pregnancy and secondary outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CIs) and were combined in a meta-analysis using the random-effects model. The heterogeneity Cochrane’s Q and the I(2) statistics were calculated. Egger’s approach to testing the significance of funnel plot asymmetry was also used.

MAIN RESULTS AND THE ROLE OF CHANCE:

The clinical pregnancy rate achieved after IVF/ICSI was 123/304 (40.5%) women with adenomyosis versus 628/1262 (49.8%) in those without adenomyosis. The RR of clinical pregnancy ranged from 0.37 (95% CI, 0.15-0.92) to 1.20 (95% CI, 0.58-2.45), with a significant heterogeneity among studies (I(2) = 56.8%, P = 0.023). Pooling of the results yielded a common RR of 0.72 (95% CI, 0.55-0.95). A funnel plot showed no indication of asymmetry among studies (Egger’s test, P = 0.696). In a meta-regression model, no association was observed between prevalence of endometriosis and the likelihood of clinical pregnancy. Three studies reported the pregnancy rate per cycle. The common RR was 0.71 (95% CI, 0.51-0.98; I(2) = 78.1%, P = 0.010). The RR observed in a study with donated oocytes was 0.90 (95% CI, 0.75-1.08). The number of miscarriages per clinical pregnancy was reported in seven studies. A miscarriage was observed in 77/241 women with adenomyosis (31.9%) and in 97/687 in those without adenomyosis (14.1%). The RR of miscarriage ranged from 0.57 (95% CI, 0.15-2.17) to 18.00 (95% CI, 4.08-79.47) (I(2) = 67.7%, P = 0.005). Pooling of the results yielded a common RR of 2.12 (95% CI, 1.20-3.75).

LIMITATIONS, REASONS FOR CAUTION:

Qualitative and quantitative heterogeneity among studies was high. At sensitivity analysis, I(2) statistic regarding the main outcome was reduced under the 50% threshold removing one trial, but the resulting confidence interval crossed unity. Also the confidence interval of the common RR of the four studies reporting only one IVF/ICSI cycle included unity. Only part of the studies could be included in the assessment of secondary outcomes.

WIDER IMPLICATIONS OF THE FINDINGS:

Adenomyosis appears to impact negatively on IVF/ICSI outcome owing to reduced likelihood of clinical pregnancy and implantation, and increased risk of early pregnancy loss. Screening for adenomyosis before embarking on medically assisted reproductive procedures should be encouraged. The potentially protective role of long down-regulation protocols needs further evaluation. In future studies on the association between adenomyosis and IVF/ICSI outcome, a matched case-control design should be adopted, live birth should be the default primary outcome and only the results regarding the first cycle should be considered.

 

 

J Laparoendosc Adv Surg Tech A. 2014 Mar;24(3):165-70.

Safety and effect on quality of life of laparoscopic Douglasectomy with radical excision for deeply infiltrating endometriosis in the cul-de-sac.

Hong DG1Kim JYLee YHChong GOCho YLLee YS.

Abstract

OBJECTIVE:

To evaluate the safety and effects on health-related quality of life (HRQOL) of radical excision of deeply infiltrating endometriosis (DIE) in the cul-de-sac.

PATIENTS AND METHODS:

This study included 390 patients with pathologically proven DIE in the cul-de-sac who underwent laparoscopic surgery between January 2000 and December 2011. The preoperative and postoperative visual analog scale (VAS) pain scores and HRQOL data from the 36-item Short Form (SF-36) questionnaire were recorded in 343 patients. Surgical outcomes, complications, and HRQOL were compared between patients who underwent hysterectomy and those who did not. Data were analyzed using the paired t test, Student’s t test, and Pearson’s correlation analysis.

RESULTS:

In the group overall, the VAS pain score and all SF-36 scales improved after surgery. In patients who underwent hysterectomy, all SF-36 scales improved except physical functioning, role-physical, general health, and vitality. In patients who did not undergo hysterectomy, all SF-36 scales improved except general health. There were significant associations between gonadotropin-releasing hormone agonist therapy and SF-36 mental health, SF-36 mental component summary, and oral medication use. The VAS pain score and SF-36 body pain score showed the greatest improvement, and the SF-36 general health score showed the least improvement. Patients who underwent hysterectomy had more severe disease and poorer surgical outcomes than those who did not undergo hysterectomy.

CONCLUSIONS:

Laparoscopic radical excision of DIE in the cul-de-sac is safe and significantly improves HRQOL, especially in terms of pain. The severity of endometriosis may affect the degree of improvement in HRQOL scores.

 

 

Erratum in: Fertil Steril. 2015 Aug;104(2):498

Treatment of pelvic pain associated with endometriosis: a committee opinion.

Practice Committee of the American Society for Reproductive Medicine.

 

Abstract

Pain associated with endometriosis may involve many mechanisms and requires careful evaluation to confirm the diagnosis and exclude other potential causes. Both medical and surgical treatments for pain related to endometriosis are effective, and choice of treatment must be individualized. This document replaces the document by the same name last published in 2008 (Fertil Steril 2008;90:S260-9).

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 May;176:39-43.

Bladder endometriosis: characterization by magnetic resonance imaging and the value of documenting ureteral involvement.

Krüger K1Gilly L2Niedobitek-Kreuter G3Mpinou L4Ebert AD4.

Abstract

OBJECTIVES:

To characterize bladder endometriosis by MRI and assess aspects of ureteral involvement.

STUDY DESIGN:

From 2007 to 2013, bladder endometriosis was diagnosed, surgically treated and histopathologically verified in 18 patients (mean age 31.7±4.6 years) retrospectively enrolled under a published MRI protocol at our hospital’s Endometriosis Center. Preoperatively, to diagnose disease spread, cystoscopy was performed and MRI in the following sequences: T2-TSE and T1-SE with and without fat saturation in the sagittal and transversal planes after rectovaginal opacification. Nine patients additionally underwent a diffusion-weighted sequence, including calculation of the apparent diffusion coefficient (ADC). By consensus, two experienced radiologists, without prior knowledge of the surgical or cystoscopic findings, retrospectively characterized bladder endometriosis on the MRI scans, also determining anatomic position, size, sequence-dependent features and incidence of hemorrhages, and calculating ADC. The scans were also investigated to determine if MRI could detect ureteral involvement intercurrent with bladder endometriosis.

RESULTS:

Endometriosis localizations were bladder roof, n=1 (5.6%) and back wall, n=17 (94.4%). Mean lesion size was 3.65±1.5ml. Lesions exhibited a lower signal intensity in T2- than in T1-weighted images. High-signal-intensity spots showed an occurrence of 72.2% in fat-suppressed T1-weighted and 61.1% in T2-weighted sequences. Mean ADC was 1251.6±220.9mm(2)/s. By MRI, it was not possible to differentiate wall layers and hence infiltration depth. The bladder endometriosis of two women showed direct involvement with the right ureter. Furthermore, one woman had endometriosis of the left distal ureter in addition to bladder endometriosis. All cases of ureteral involvement were detected by MRI.

CONCLUSIONS:

Characteristic MRI features of bladder endometriosis were found to be low signal intensity in T2-weighted and high-signal-intensity spots in T1- and T2-weighted sequences. Standard-sequence MRI was capable of detecting ureteral involvement, but not bladder wall infiltration depth.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 May;176:25-30.

A red fluorescent nude mouse model of human endometriosis: advantages of a non-invasive imaging method.

Wang N1Hong S2Tan J3Ke P3Liang L3Fei H3Liu B3Liu L4Liu Y5Yu B6.

Abstract

OBJECTIVES:

To establish red fluorescent human endometriosis lesions in a nude mouse model and dynamically and non-invasively to compare intraperitoneal and subcutaneous injection models.

STUDY DESIGN:

Primary cultures of endometrial stromal cells (ESCs) and epithelial cells (EECs) isolated from 24 patients with a normal uterine cavity were transfected with 2.5×10(8) (Group 1) and 1.25×10(8) (Group 2) plaque-forming units (PFU) of adenovirus encoding red fluorescent protein (Ad-RFP). Transfection efficiencies, fluorescence intensity and apoptosis rate of the two types of cells were compared in vitro. A mixture of 2.5×10(8) PFU Ad-RFP-infected approximately 400 EECs cell mass and 2×10(6) ESCs for 36h was injected individually into 24 female nude mice subcutaneously (Group A) or intraperitoneally (Group B). From Day 5 after injection, an in vivo imaging system (IVIS) was used to non-invasively observe and compare the lesions of the two groups every week until Day 33. Specifically, the fluorescent intensity, positive rates, persistence time and lesion weight in the implanted human endometriosis lesions were compared. A parametric Student’s t-test and two-way analysis of variance were used for statistical analysis.

RESULTS:

Compared with 1.25×10(8) PFU RFP, a titre of 2.5×10(8) PFU RFP ESCs and EECs incubated for 36h exhibited higher transfection efficiencies and higher fluorescence intensities in vitro. In vivo imaging of the fluorescent human endometriosis lesions originating from an RFP titre of 2.5×10(8) PFU showed that the intensity and lesion weight in Group A were significantly higher than in Group B. However, the two groups had the same RFP-positive rates and fluorescence persistence. The structure of each lesion was evaluated by immunohistochemistry to confirm its human endometrial origin.

CONCLUSIONS:

The red fluorescent human endometriosis model established by subcutaneously injecting 2.5×10(8) PFU RFP-transfected stromal cells and epithelial cells into nude mice had a higher fluorescent positive rate from Day 5, higher intensity and weight but the same persistence as the intraperitoneal injection model.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 May;176:31-3.

Full-thickness endometriosis of the bladder: report of 31 cases.

Kjer JJ1Kristensen J2Hartwell D3Jensen MA2.

Abstract

OBJECTIVE:

To draw attention to the rare condition of endometriosis in the bladder. This is correlated with symptoms not normally connected to endometriosis and therefore often remains underdiagnosed for years.

DESIGN AND SETTING:

Retrospective study in a university teaching hospital, one of two referral centres in Denmark for surgical treatment of stage III and IV endometriosis.

POPULATION:

Thirty-one women with deep infiltrating bladder endometriosis.

METHODS:

All women presenting in the Department of Obstetrics and Gynaecology with deep infiltrating bladder endometriosis between March 2002 and March 2011. We included only patients with symptomatic full-thickness bladder detrusor endometriosis and mucosal involvement. All patients had had bladder symptoms for two to seven years.

MAIN OUTCOME MEASURES:

Symptoms after surgery and recurrence rate.

RESULTS:

The main preoperative symptom was urinary frequency. All patients had significant relief of symptoms after operation, and none had recurrence of the bladder endometriosis judged by ultrasound or reported symptoms. Twenty-six (87%) patients had endometriosis in another location as well. Eight had nodules in the recto-vaginal septum. Complete surgical excision of all associated endometriotic lesions was carried out during the same surgical procedure. During the mean follow-up period of 59 months no long-term complications were diagnosed.

CONCLUSION:

Bladder endometriosis should be considered in patients who present with irritative urological symptoms with aggravation during menstruation or in patients with a history of endometriosis. When patients have symptoms we recommend surgical treatment in cases where medical treatment fails.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 May;176:153-7.

Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial.

Hashish NM1Badway HS1Abdelmoty HI1Mowafy A1Youssef MA2.

Abstract

OBJECTIVE:

Follicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI).

STUDY DESIGN:

One hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20-38 years; basal follicle-stimulating hormone <10mIU/ml; body mass index <35kg/m(2); and ostradiol >1000pg/ml and <4000pg/ml on the day of human chorionic gonadotrophin administration. Exclusion criteria were: evidence of endometriosis; uterine myoma; hydrosalpinges; endocrinological disorders; history of implantation failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility.

RESULTS:

Clinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant.

CONCLUSION:

Flushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI.

 

 

J Minim Invasive Gynecol. 2014 Sep-Oct;21(5):730-1.

Deep rectal shaving followed by transanal disc excision in large deep endometriosis of the lower rectum.

Roman H1Tuech JJ2Arambage K2.

Abstract

STUDY OBJECTIVE:

To report an original technique of deep rectal shaving using PlasmaJet (Plasma Surgical, Inc., Roswell, GA) followed by transanal disc excision using the Contour Transtar stapler (Ethicon EndoSurgery Inc., Cincinnati, OH) suitable in large deep endometriosis of the lower rectum.

DESIGN:

Canadian Task Force III.

SETTING:

Rouen University Hospital. The procedure was performed in a 30-year-old nullipara referred with a large endometriotic nodule infiltrating the right uterosacral ligament and the anterolateral wall of the lower rectum. Rectal infiltration measured 30 mm in diameter and was responsible for stenosis. The first step of the procedure is represented by laparoscopic deep rectal shaving performed using plasma energy exclusively, combining the detachment of the nodule from the rectum with in situ ablation of residual endometriotic foci of the shaved area. Then, transanal excision is performed by the colorectal surgeon from the rectal approach. Three of 4 traction parachute sutures are placed in the middle and outside the shaved area. Their traction induces the prolapse of the shaved rectal wall that is resected using the Contour Transtar stapler, which is a device originally destined to remove rectal prolapse. The final staple line is inspected for bleeding and secured with an interrupted resorbable suture as required. Surgical technique reports in anonymous patients are exempt from ethical approval by an institutional review board.

INTERVENTION:

Deep rectal shaving using PlasmaJet followed by transanal disc excision using Contour Transtar stapler.

MEASUREMENTS AND MAIN RESULTS:

Immediate postoperative outcomes were uneventful, and bowel movements were normal beginning with day 5. To date, this procedure was successfully performed in 17 women with large deep endometriosis of the mid and lower rectum with only favorable rectal functional outcomes.

CONCLUSIONS:

Based on our experience, we believe that our conservative technique is feasible in large low rectal endometriosis and avoids the risk of unfavorable outcomes related to low colorectal resection.

 

 

Hum Reprod Update. 2014 Jul-Aug;20(4):467-84.

The dynamics of nuclear receptors and nuclear receptor coregulators in the pathogenesis of endometriosis.

Han SJ1O’Malley BW2.

Abstract

BACKGROUND:

Endometriosis is defined as the colonization and growth of endometrial tissue at anatomic sites outside the uterine cavity. Up to 15% of reproductive-aged women in the USA suffer from painful symptoms of endometriosis, such as infertility, pelvic pain, menstrual cycle abnormalities and increased risk of certain cancers. However, many of the current clinical treatments for endometriosis are not sufficiently effective and yield unacceptable side effects. There is clearly an urgent need to identify new molecular mechanisms that critically underpin the initiation and progression of endometriosis in order to develop more specific and effective therapeutics which lack the side effects of current therapies. The aim of this review is to discuss how nuclear receptors (NRs) and their coregulators promote the progression of endometriosis. Understanding the pathogenic molecular mechanisms for the genesis and maintenance of endometriosis as modulated by NRs and coregulators can reveal new therapeutic targets for alternative endometriosis treatments.

METHODS:

This review was prepared using published gene expression microarray data sets obtained from patients with endometriosis and published literature on NRs and their coregulators that deal with endometriosisprogression. Using the above observations, our current understanding of how NRs and NR coregulators are involved in the progression of endometriosis is summarized.

RESULTS:

Aberrant levels of NRs and NR coregulators in ectopic endometriosis lesions are associated with the progression of endometriosis. As an example, endometriotic cell-specific alterations in gene expression are correlated with a differential methylation status of the genome compared with the normal endometrium. These differential epigenetic regulations can generate favorable cell-specific NR and coregulator milieus for endometriosis progression. Genetic alterations, such as single nucleotide polymorphisms and insertion/deletion polymorphisms of NR and coregulator genes, are frequently detected in ectopic lesions compared with the normal endometrium. These genetic variations impart new molecular properties to NRs and coregulators to increase their capacity to stimulate progression of endometriosis. Finally, post-translational modifications of NR coregulators, such as proteolytic processing, generate endometriosis-specific isoforms. Compared with the unmodified coregulators, these coregulator isoforms have unique functions that enhance the pathogenesis of endometriosis.

CONCLUSIONS:

Epigenetic/genetic variations and posttranslational modifications of NRs and coregulators alter their original function so that they become potent ‘drivers’ of endometriosis progression.

 

 

Am J Reprod Immunol. 2014 Aug;72(2):148-57.

Recent advances in understanding endometrial receptivity: molecular basis and clinical applications.

von Grothusen C1Lalitkumar SBoggavarapu NRGemzell-Danielsson KLalitkumar PG.

 

Abstract

Advancement in the field of ART has lead to the possibility of achieving good quality embryos. However, the success rate in ART needs further improvement. This is largely dependent on identifying the receptive endometrium for the successful implantation of embryos as well as modulating the endometrium to the receptive stage. In the last half-a-decade, focus has been shifting toward identifying the receptive endometrium. Here, we summarize different tools explored to identify receptive endometrium from the literature, mainly focusing on the past decade, with the help of PubMed. The quest to identify endometrial receptivity markers has lead to the exploration of morphological features at micro and macro scale levels. A large number of studies at molecular levels have focused on genomic, proteomic and lipidomic targets. Recent development of endometrial receptivity array is a promising diagnostic instrument. However, a noninvasive possibility for the diagnosis of endometrial receptivity would be an ideal tool, which could be used in the clinic to improve the success rate of ART. Improved knowledge on endometrial receptivity will not only help to improve the diagnosis and treatment of infertility but will also give possibilities to develop new contraceptive methods targeting the endometrium.

 

 

Mol Med Rep. 2014 May;9(5):1483-505.

Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (review).

Kobayashi H1Imanaka S1Nakamura H1Tsuji A1.

 

Abstract

Endometriosis is a complex disease influenced by genetic, epigenetic and environmental factors. The aim of the present study was to describe genomic instability, genetic polymorphisms and their haplotype, epigenetic alterations associated with predisposition to endometriosis, and the key factors associated with endometriosis-related ovarian neoplasms. Focus has been given on the developing paradigm that epigenetic alterations or genetic mutations in endometriosis may start in utero or in adolescent and young adults. A search was conducted between 1966 and 2010 through the English language literature (online Medline PubMed database) using the keywords endometriosis combined with epigenetic, genetic and environment. Genetic/epigenetic alterations include single‑nucleotide polymorphisms (SNPs), copy number variation, loss of heterozygosity (LOH), and promoter methylation. Several genes with genetic polymorphisms analyzed in the present study tended to overlap previously reported endometriosis susceptibility genes. Retrograde menstruation leads to iron overload, which facilitates the accumulation of somatic mutations through Fenton reaction-mediated oxidative stress. The epigenetic disruption of gene expression plays an important role in the development of endometriosis through interaction with environmental changes. There seems to be at least three spatiotemporally distinct phases of the development of endometriosis: the initial phase of genetic background inherited from parents; followed by epigenetic modifications in the female offspring; and iron overload, which is subject to dynamic modulation later in life. In conclusion, the marked regulation of endometriosis susceptibility genes may stem from a mechanism responsible for epigenetic and genetic mutations based on the microenvironmental changes.

 

 

Ultrasound Obstet Gynecol. 2014 Sep;44(3):261-78.

Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis.

Barbosa MA1Teixeira DMNavarro PAFerriani RANastri COMartins WP.

Abstract

OBJECTIVE:

To evaluate whether the presence or severity of endometriosis affects the outcome of assisted reproductive techniques (ART).

METHODS:

In this systematic review, all studies comparing the outcome of ART in women with and those without endometriosis, or at different stages of the disease, were considered eligible. We used either risk ratio (RR) or mean difference (MD) and their 95%CIs for comparisons. The primary outcome was live birth; the secondary outcome was clinical pregnancy. Miscarriage and the number of oocytes retrieved were examined as additional outcomes.

RESULTS:

We included 92 studies in the review and 78 in the meta-analysis: 20,167 women with endometriosiswere compared with 121,931 women without endometriosis, and 1703 women with Stage-III/IV endometriosiswere compared with 2227 women with Stage-I/II endometriosis. The following results were observed for the comparison of women with endometriosis vs women without endometriosis: live birth, RR = 0.99 (95%CI, 0.92-1.06); clinical pregnancy, RR = 0.95 (95%CI, 0.89-1.02); miscarriage, RR = 1.31 (95%CI, 1.07-1.59); number of oocytes retrieved, MD = -1.56 (95%CI, -2.05 to -1.08). The following results were observed for the comparison of women with Stage-III/IV vs Stage-I/II endometriosis: live birth, RR = 0.94 (95%CI, 0.80-1.11); clinical pregnancy, RR = 0.90 (95%CI, 0.82-1.00); miscarriage, RR = 0.99 (95%CI, 0.73-1.36); number of oocytes retrieved, MD = -1.03 (95%CI, -1.67 to -0.39).

CONCLUSIONS:

Women with endometriosis undergoing ART have practically the same chance of achieving clinical pregnancy and live birth as do women with other causes of infertility. No relevant difference was observed in the chance of achieving clinical pregnancy and live birth following ART when comparing Stage-III/IV with Stage-I/II endometriosis. The quality of the evidence for the additional examined outcomes was very low, not allowing meaningful conclusions to be drawn.

 

 

Iran J Reprod Med. 2013 Dec;11(12):983-8.

Effect of intramural myomectomy on endometrial HOXA10 and HOXA11 mRNA expression at the time of implantation window.

Alizadeh Z1Faramarzi S2Saidijam M3Alizamir T4Esna-Ashari F5Shabab N3Farimani Sanoee M1.

Abstract

BACKGROUND:

HOXA11 and HOXA10 are expressed in endometrium throughout the menstrual cycle and show a dramatic increase during the mid-luteal phase at the time of implantation. The expression of these genes is decreased in women with myomas.

OBJECTIVE:

To determine whether myomectomy would reverse HOXA11 and HOXA10 expression, we evaluated the transcript levels of these genes in the endometria of patients before and after myomectomy.

MATERIALS AND METHODS:

Expression of HOXA11 and HOXA10 were examined prospectively during the midluteal phase in endometrium obtained from infertile women (n=12) with myoma before and three months after myomectomy. Endometrial HOXA11 and HOXA10 expression were evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTS:

Endometrial HOXA11 and HOXA10 mRNAs expression levels (normalized to 18SrRNA) were increased insignificantly in endometrium of patients after myomectomy (p=0.7 and p=0.15 respectively).

CONCLUSION:

The results suggest that the alteration in expression pattern of these genes could not account for some aspects of fertility after myomectomy. This article extracted from M.Sc. thesis. (Shamila Faramarzi).

 

 

Iran J Reprod Med. 2013 Mar;11(3):179-84.

Assessing the efficacy of aspiration and ethanol injection in recurrent endometrioma before IVF cycle: A randomized clinical trial.

Aflatoonian A1Rahmani E2Rahsepar M1.

Abstract

BACKGROUND:

Endometriosis is a common hormone-dependent gynecologic disease with a high recurrence. Laparotomy or laparoscopy is the standard surgery for the large endometrioma. Also, sclerotherapy is basically used to treat different diseases one of which is endometrioma.

OBJECTIVE:

The study was designed to assess the value of transvaginal ultrasound-guided ethanol sclerotherapy in patients with a recurrent endometrioma.

MATERIALS AND METHODS:

In a randomized clinical trial, an interventional group of 20 patients underwent transvaginal ethanol sclerotherapy for recurrent ovarian endometrioma. The patients were followed up first after one and two weeks and then after one, two, and three months. If the patients had no endometrioma, they were treated with in vitro fertilization (IVF) (standard long protocol). A control group of 20 patients with endometrioma were enrolled for an IVF protocol. They had no treatment by ethanol sclerotherapy. IVF parameters, pregnancy rates, and implantation rates were compared in both groups.

RESULTS:

The demographic data showed no difference between the two groups. The initial mean endometria size was 41.45±15.9 cm, the recurrence rate after 6 months was 4 (20%), FSH before and after sclerotherapy was 6.97±2.25 IU/L and 6.78±1.88 IU/L (p=0.343). The clinical pregnancy rate was 6 (33.3%) vs. 3 (15%), (p=0.616). The fertilization rate emerged 63.06% in study group vs. 60.38%, (p=0.57). The implantation rate turned out 12.9% in study group vs. 7.5%, (p=0.52). None of these results were significant. However, the data pointed to a better trend toward the ethanol sclerotherapy group.

CONCLUSION:

Ethanol sclerotherapy could be an effective strategy for the treatment of recurrent endometrioma especially before IVF.

 

 

 

Iran J Reprod Med. 2013 May;11(5):399-404

Study of ultrastructure and apoptosis in the endometrium of women with or without endometriosis.

Roshangar L1Abdollahifard S2Majdi A3Zarrintan A3Ghasemzade A2Farzadi L2Soleimani Rad S2Soleimani Rad J4.

Abstract

BACKGROUND:

More than 40% of infertilities are due to endometriosis. Ultrustructural and histochemical study of endometrium will help to clarify the etiology of endometriosis.

OBJECTIVE:

The aim of the present study was to investigate the ultrastructure and occurrence of apoptosis in endometrial cells of women with or without endometriosis.

MATERIALS AND METHODS:

In the present case-control study, endometrial specimens from 12 women without endometriosis (as control) and 12 women with endometriosis (as case) were examined. Specimens for control group were obtained from the patients that were referred to gynecology hospital for hysterectomy due to various reasons. In case group the endometriosis was diagnosed according to laparoscopy and endometrial samples were taken using pippel biopsy. The specimens from both case and control groups were processed for Transmission Electron Microscopy (TEM), TUNEL reaction technique and morphometric studies.

RESULTS:

The results show that endometrial epithelium lost its continuity in women with endometriosis and endometrial cells have euchromatic nucleus in comparison to those from non-endometriosis. There were several apoptotic cells in the luminal and glandular endometrial epithelium and stroma from endometrium of control group. However, apoptotic cells were rarely seen in the endometrium from women with endometriosis. The difference in number of apoptotic cells between two groups statically was significant (p<0.001).

CONCLUSION:

Regarding the ultrastructural characteristics of endometrial epithelial cells and comparison of apoptotic occurrence in control and case groups it is concluded that endometrial cells in endometriosis group have higher potential to survive and possibly implant.

 

 

Iran J Reprod Med. 2013 May;11(5):405-14.

The importance of endometrial nerve fibers and macrophage cell count in the diagnosis of endometriosis.

Cetin C1Serdaroglu H2Tuzlali S3.

Abstract

BACKGROUND:

Endometriosis is a disease that is hard to diagnose without the gold standard method, laparoscopy. An easier diagnostic method is needed.

OBJECTIVE:

The aim of the study is to determine whether the number of macrophage cells in the endometrium and/or the detection of nerve fibers can be used in the diagnosis of endometriosis.

MATERIALS AND METHODS:

Endometrial sampling was done to 31 patients prior to laparoscopy (L/S) or laparotomy (L/T) at Istanbul University Istanbul School of Medicine Hospital between January 2010 February 2011. Also 34 patients who were retrospectively chosen from their files were added to the study. 5 patients were excluded from the study. Totally, 31 patients were placed in the endometriosis and 29 patients in the control group. Endometrial samples were evaluated immunohistochemically with the markers protein gene product 9.5 (PGP 9.5) and neurofilament (NF) for nerve fibers and CD68 for macrophages.

RESULTS:

None of the samples were stained with PGP 9.5 and NF. As for CD68+cells, no statistically significant difference was observed between groups (endometriosis: 216.10±104.41; control: 175.93±43.05, p=0.06). RESULTS were also evaluated in the subgroups of menstruel phases and disease stages. Only in the proliferative phase there was a significant increase in the endometriosis group (p=0.03). No significant difference was observed between the stages.

CONCLUSION:

The detection of nerve fibers in the eutopic endometrium with the markers of PGP 9.5 and NF is not found to be helpful in the diagnosis of endometriosis. Macrophage cells may be helpful in the diagnosis only in the proliferative phase.

 

 

Iran J Reprod Med. 2013 May;11(5):415-22.

Curcumin inhibits endometriosis endometrial cells by reducing estradiol production.

Zhang Y1Cao H2Yu Z1Peng HY1Zhang CJ1.

Abstract

BACKGROUND:

Endometriosis is a complex estrogen-dependent disease that is defined as the presence of endometrial gland and stroma outside the uterine cavity. Although the exact mechanism for the development of endometriosis remains unclear, there is a large body of research data and circumstantial evidence that suggests a crucial role of estrogen in the establishment and maintenance of this disease.

OBJECTIVE:

This study is an attempt to assess the effect of curcumin on inhibiting endometriosis endometrial cells and to investigate whether such an effect is mediated by reducing estradiol production.

MATERIALS AND METHODS:

Endometriotic stromal cells, normal endometrial stromal cells, endometriotic epithelial cells and normal endometrial epithelial cells were isolated and cultured. E2 value of cells and the effect of curcumin on cell proliferation were evaluated. Finally, effect of curcumin on E2 assay was detected.

RESULTS:

Electrochemiluminescence immunoassay results showed that E2 value of endometriotic epithelial cells was higher than the endometriotic stromal cells (p=0.037), while the expression of E2 in normal endometrial stromal and epithelial cells was extremely low. WST-8 result showed, compared with endometrial stromal cells, ectopic endometriotic stromal cells had a higher growth rate. After intervene with curcumin (10μmol/L, 30μmol/L and 50μmol/L) for 0-96h, the number of endometriotic stromal cells was reduced and cells growth slowed, compared with 0μmol/L group. Compared with 0μmol/L group, E2 level was lower after treatment with curcumin, especially in 30μmol/L and 50μmol/L group.

CONCLUSION:

In summary, in this study we found that E2 is important in ectopic endometrium, and epithelial cell is in dominant position with E2 secretion. Curcumin was able to suppress the proliferation of endometrial cells by reducing the E2 value.

 

 

Iran J Reprod Med. 2013 Jun;11(6):473-8.

Association of TP53 gene codon 72 polymorphism with endometriosis risk in Isfahan.

Nikbakht Dastjerdi M1Aboutorabi R1Eslami Farsani B1.

Abstract

BACKGROUND:

Endometriosis is a female health disorder that occurs when cells from the lining of the uterus grow in other areas of the body. The cause of endometriosis is unknown.

OBJECTIVE:

The purpose of this study was to investigate TP53 gene codon 72 polymorphism in women with endometriosis and compared it with healthy samples in Isfahan.

MATERIALS AND METHODS:

We undertook a case-control study to examine the possible association of the TP53 gene codon 72 polymorphism with the risk of endometriosis in Isfahan. Ninety whole blood specimens from normal people as controls and ninety endometriosis specimens were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction.

RESULTS:

Frequency of genotype Arg/Arg (Arginine/Arginine) in the samples of endometriosis was 28.9% and in healthy samples 42.2%. Frequency of genotype Pro/Pro (Proline/Proline) in the samples of endometriosiswas 15.6% and in healthy ones. Frequency of heterozygote’s Arg/Pro was 55.6% in endometriosis samples and 54.45% in healthy ones 3.3%. By comparing statistical genotype Pro/Pro with two other genotypes in both groups there was a statistical meaningful difference between control group and endometriosis group. [p=0.009, CI=95%, OR=5.34 (1047-19.29)].

CONCLUSION:

Recent research shows that genotype Pro/Pro codon72 exon4 TP53 gene may be one predisposing genetic factor for endometriosis in Isfahan.

 

 

Iran J Reprod Med. 2013 Aug;11(8):677-80.

Pelvic abscess after oocyte retrieval in women with endometriosis: A case series.

Romero BAibar L1Martínez Navarro LFontes JCalderón MAMozas J.

Abstract

BACKGROUND:

Pelvic inflammatory disease with progression to pelvic abscess is a rare complication after oocyte retrieval during in vitro fertilization cycles. However, in patients with endometriosis the risk appears to be increased. Many authors agree on the need for antibiotic prophylaxis during the oocyte retrieval in these patients, but there is no consensus regarding the best antibiotic.

CASE:

We discuss 3 clinical cases of tubo-ovarian abscess in women with endometriosis after oocyte retrieval despite antibiotic prophylaxis between 2004 and 2011 at our center, and discuss our experience in the context of earlier reports.

CONCLUSION:

It is unclear whether antibiotic prophylaxis is necessary in these women, and which antibiotic is best. Only douching with povidone-iodine appears to decrease the rate of pelvic infection.

 

 

Gynecol Endocrinol. 2014 Jul;30(7):520-4.

Increased levels of biglycan in endometriomas and peritoneal fluid samples from ovarian endometriosis patients.

Kocbek V1Hevir-Kene NBersinger NAMueller MDRižner TL.

 

Abstract

In our previous low-density-array gene-expression analysis we found an increased expression of biglycan gene in ovarian endometriosis patients. In the present study we evaluated biglycan expression at the protein level in tissue, serum and peritoneal fluid (PF) from ovarian endometriosis patients, patients with benign ovarian cysts and healthy women. Twenty samples of endometriomas and 27 of control tissues (benign ovarian cysts and eutopic endometrium of healthy women) were obtained laparoscopically or by curettage. Serum and PF samples were collected from 56 ovarian endometriosis patients and 40 controls (patients with benign cysts and healthy women). Tissue biglycan levels and serum and PF biglycan concentrations were determined by Western blotting and ELISA, respectively. Biglycan was detected in endometriomas and in benign cysts tissues but differed in glycosylation levels. The PF biglycan concentrations were significantly increased in ovarian endometriosis patients (mean ± SD=220.3 ± 190.5 pg/mg protein) compared to the whole control group (101.9 ± 94.7 pg/mg protein, p<0.001), while serum concentrations did not differ significantly. Biglycan appears to be involved in ovarian pathologies and probably has different roles in benign cysts as compared to ovarian endometriomas.

 

 

Gynecol Oncol. 2014 Jun;133(3):480-4.

Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study.

Scarfone G1Bergamini A2Noli S1Villa A1Cipriani S3Taccagni G4Vigano’ P5Candiani M2Parazzini F3Mangili G6.

Abstract

OBJECTIVE:

Endometrioid and clear cell ovarian tumors have been referred to as “endometriosis associated ovarian cancers”. However, very few studies have compared clinical and prognostic features of endometriosis-associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database.

METHODS:

Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n=27 and n=46, respectively). Clinical and pathological data have been compared.

RESULTS:

Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4±10.0 and 58.4±11.2years, p=0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p=0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates.

CONCLUSIONS:

Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading.

 

 

Gynecol Obstet Invest. 2014;77(3):201-4.

A rare familial case of endometriosis with very severe gynecological and obstetric complications: novel genetic variants at a glance.

Buggio L1Pagliardini LGentilini DDe Braud LViganò PVercellini P.

 

Abstract

Endometriosis is influenced by both genetic and environmental factors. Genetic factors make up about half of the variation in endometriosis. Nevertheless, the genetics of endometriosis remains complex and in part unsolved, but recently, based on the results of few genome-wide association studies, some genetic susceptibility loci have been identified as associated robustly with the disease, providing new insights into potential pathways leading to endometriosis. Here, we present the case of a familial cluster composed by 3 sisters and their mother, all affected by endometriosis. Very severe gynecological and obstetric complications caused by the invasiveness of the disease have been observed in all members of the single family. The entire family has been genotyped for 3 single-nucleotide polymorphisms identified as associated with endometriosis. All the family members were homozygotes for the risk allele G for the rs1333049 variant in the CDKN2BAS locus. The genotype-phenotype association is just at the beginning of endometriosis research promising to face novel concepts for disease diagnosis and treatment.

 

 

J Cell Physiol. 2014 Nov;229(11):1731-5.

Serum biomarker for diagnosis of endometriosis.

Signorile PG1Baldi A.

 

Abstract

Endometriosis is estimated to affect 10% of women during the reproductive years. The lack of a non-invasive diagnostic test significantly contributes to the long delay between onset of the symptoms and definitive diagnosis of endometriosis. This case-control study was conducted to identify specific endometriosis antigens using 2D gel analysis in women with endometriosis (n = 5) and without endometriosis (n = 5). Differentially expresses spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry (nanoLC-ESI-MS/MS) with MASCOT analysis, in order to identify the corresponding proteins. ELISAs were performed on a different cohort of endometriosis (n = 120) and healthy patients (n = 20) in order to confirm the differential expression of the identified proteins. ROC analysis of ELISA results confirmed the statistical significance of the differential expression for one of these proteins: Zn-alpha2-glycoprotein (P = 0.019). We propose the analysis of the expression level of this protein in the serum as a new non-invasive diagnostic test for endometriosis.

 

 

J Fam Plann Reprod Health Care. 2014 Apr;40(2):133-41

Evolution of extended use of the combined oral contraceptive pill.

Panicker S1Mann SShawe JStephenson J.

Abstract

BACKGROUND:

Extended use of the combined oral contraceptive pill (COC), defined as taking active pills for at least 28&emsp14;days, has been used in order to avoid bleeding at important times and to treat gynaecological conditions such as endometriosis. We examined the main issues involved in extended use of the COC and how it has evolved from being one of medicine’s best-kept secrets to becoming more widely accepted by women and the medical community.

STUDY DESIGN:

Literature review, using Medline, Embase, Pubmed, CINHAL Plus, the Cochrane Database of Systematic Reviews and the Ovid database for all relevant clinical trials, systematic reviews, meta-analyses, literature reviews, scientific papers and individual opinions between 1950 and October 2013.

RESULTS:

Accumulating evidence supports various forms of extended pill use as suitable alternatives to the standard (21/7) regimen. In terms of user preference, much hinges on whether women wish to reduce the frequency or duration of scheduled bleeding on the combined pill. Available data on the safety of extended pill regimens do not give cause for concern, but longer term data should be collected.

CONCLUSIONS:

Information for women considering extended COC regimens should keep pace with research findings to ensure that women and clinicians are better informed about the choices available.

 

 

J Cytol. 2013 Oct;30(4):280-3.

Cytopathological features of scar endometriosis mimicking an adenocarcinoma: A diagnostic pitfall.

Rekhi B1Sugoor P2Patil A1Shylasree TS2Kerkar R2Maheshwari A2.

 

Abstract

Scar endometriosis can be a diagnostic challenge in fine-needle aspiration cytology (FNAC) smears that at times, is the first diagnostic modality in such cases. The challenge is amplified when the clinical details are limited and cytopathological features reveal nuclear atypia. A 33-year-old lady presented with an abdominal swelling that she noticed after she met with a scald. Clinically, the swelling was located lateral to her 3-year-old pfannenstiel incision scar. The initial diagnosis on FNAC was metastatic adenocarcinoma. On review, smears were hypercellular, comprising epithelial cells in groups and focally, regular glandular arrangements, imperceptibly admixed with numerous, relatively smaller, short spindly cells. Epithelial cells exhibited mild to focally, moderate nuclear enlargement/atypia. Subsequent biopsy and excision revealed endometrial glands exhibiting focal nuclear atypia with adjacent stroma. Diagnosis of endometriosis was offered. The results were reinforced with positive estrogen receptor staining in the glands and stroma, along with CD10 positivity in the stroma. The patient was recommended gonadotropin releasing hormone analogs and is presently free of disease a year after her diagnosis. FNAC can be a pitfall in the diagnosis of endometriosis. Correct diagnosis has significant therapeutic implications. Although presence of atypia in such cases should not delude the diagnosing cytopathologist for consideration of endometriosis, it should be documented. The value of clinical history in such cases cannot be overemphasized.

 

 

Rev Prat. 2014 Jan;64(1):87-91.

Intrauterine insemination.

Merviel PCabry RLourdel EBarbier FScheffler FMansouri NDevaux ABenkhalifa MCopin H.

 

Abstract

The intrauterine insemination with husband’s sperm is an assisted reproductive technologie, as proposed in the case of cervical infertility, moderate male infertility, dysovulation, mild or moderate endometriosis or unexplained infertility. In the last three indications the ovarian stimulation is necessary. The couple demographic criteria (age of both partners, lifestyle, duration of infertility) and the results of the infertility evaluation (ovarian reserve, uterus, spermogram-spermocytogram) increase the chances of pregnancy by intrauterine insemination with husband’s sperm and reduce the risk of multiple pregnancies. Pregnancy rates observed ranged from 8 to 20% per cycle according to indications.

 

 

Expert Rev Mol Diagn. 2014 Apr;14(3):365-85

Noninvasive biomarkers of endometriosis: myth or reality?

Rižner TL.

 

Abstract

Endometriosis affects 10% of premenopausal women and 35-50% of women with infertility, pelvic pain, or both. At present, endometriosis can only be diagnosed with surgery, where laparoscopy is considered a gold standard. Noninvasive biomarkers are thus urgently needed. In 2010, the peripheral biomarkers of endometriosis were systematically reviewed by May et al. However, with the introduction of ‘-omics’ technologies, we have witnessed immense progress in biomarker discovery, which now calls for an overview of recent studies. This report looks at potential blood and urine biomarkers of endometriosis published in the last 3 years. The current status of noninvasive diagnostic biomarkers of endometriosis is discussed, with the limitations of these studies identified and recommendations for future biomarker discovery provided.

 

 

Int J Surg Pathol. 2014 Aug;22(5):421-6.

Endomyometriosis (“Uterus-like mass”) in an XY Male: Case Report With Molecular Confirmation and Literature Review.

González RS1Vnencak-Jones CL1Shi C1Fadare O2.

 

Abstract

Male endometriosis and endomyometriosis (also termed “uterus-like mass”) are 2 unusual manifestations of endometriosis. We report a case of male endomyometriosis with immunohistochemical and molecular confirmation. A 52-year-old man presented with stabbing pelvic pain. Computed tomography scan showed a mass in the right inguinal area, at the site of prior hernia repair. The lesion was tubular in shape, with a thick muscular wall and a central blood-filled lumen. Microscopically, the tissue showed layers of concentric smooth muscle, with endometrial glands and stroma lining the lumen. Many theories have been proposed regarding the etiology of both endomyometriosis and male endometriosis, including remnant rests of Müllerian tissue and metaplasia. Cases of male endometriosis typically have been linked to estrogen therapy for prostate cancer. Our patient had a history of cirrhosis and took spironolactone, possibly leading to an altered hormonal state that interacted with a reactive/metaplastic process at a site of prior surgery.

 

 

J Clin Endocrinol Metab. 2014 Jul;99(7):E1191-8.

Peroxisome proliferator-activated receptor gamma, coactivator 1α enhances local estrogen biosynthesis by stimulating aromatase activity in endometriosis.

Suganuma I1Mori TIto FTanaka YSasaki AMatsuo SKusuki IKitawaki J.

Abstract

CONTEXT:

Endometriosis is an estrogen-dependent disease, and estrogen is overproduced by abnormally elevated aromatase in endometriotic tissues. Peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC-1α) is a transcriptional coactivator-modulating steroid hormone.

OBJECTIVE:

To investigate the effect of PGC-1α on aromatase activity in endometriosis.

DESIGN:

Specimens from ovarian endometrioma (OE), endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for PGC-1α and aromatase expression. PGC-1α-dependent changes in aromatase expression in primary cultured stromal cells (SCs) were identified using luciferase and enzymatic assays, exon I-specific RT-PCR, and real-time PCR. Environmental stimulus-induced changes in PGC-1α were also examined.

RESULTS:

PGC-1α was more highly expressed in OE than in EE and NE (P < .01). In OE, PGC-1α was coexpressed with aromatase, and their mRNA expressions were also correlated (r = 0.56, P = .02). PGC-1α was recruited to the nuclear receptor half-site between PI.3 and PII in the aromatase promoter. PGC-1α overexpression enhanced aromatase promoter activity (P < .01), mRNA expression (P < .05), and enzymatic activity (P < .01) in SCs from OE, but not in SCs from EE or NE. The levels of PI.3, PII, and exon II mRNA increased and transcriptional enhancement was abolished by mutation of the PGC-1α-interacting site. PGC-1α expression was enhanced in SCs from OE by tumor necrosis factor (TNF)-α (P < .05) but not by hypoxia or 17β-estradiol.

CONCLUSIONS:

PGC-1α stimulated by TNF-α regulates aromatase expression and activity to promote local estrogen biosynthesis in OE, suggesting that PGC-1α is a promising candidate for novel targeted therapies in endometriosis treatment.

 

Lascia un commento

Cerca

Utilizzando il sito, accetti l'utilizzo dei cookie da parte nostra. maggiori informazioni

Questo sito utilizza i cookie per fornire la migliore esperienza di navigazione possibile. Continuando a utilizzare questo sito senza modificare le impostazioni dei cookie o cliccando su "Accetta" permetti il loro utilizzo.

Chiudi