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J Minim Invasive Gynecol. 2014 Jan-Feb;21(1):101-8.

Determining the fertility benefit of controlled ovarian hyperstimulation with intrauterine insemination after operative laparoscopy in patients with endometriosis.

Gandhi AR1Carvalho LF2Nutter B3Falcone T4.




To determine the fertility benefit of controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) in surgically treated endometriosis.


Retrospective cohort study (Canadian Task Force classification II-2).


Cleveland Clinic Foundation, tertiary care center.


Ninety-six women of reproductive age who underwent operative laparoscopy to treat endometriosis-related infertility (endometriosis stage I/II n = 67; stage III/IV n = 29) from 2001 to 2011 at the Cleveland Clinic Foundation.


COH via letrozole, clomiphene, or gonadotropins, with or without IUI.


Kaplan-Meier estimations of cumulative pregnancy rates were compared by stage between COH/IUI and spontaneous cycles. Patients with stage I/II endometriosis attempted spontaneous pregnancy for 669 months and 216 COH + IUI cycles, and patients with stage III/IV endometriosisattempted spontaneous pregnancy for 379 months and 74 COH + IUI cycles. Crude pregnancy rates were 45.7% in stage I/II and 40.5% in stage III/IV. Twelve-month cumulative pregnancy rates in stage I/II were 45% for spontaneous attempts and 42% for COH + IUI, and in stage III/IV were 20% for spontaneous attempts and 10% for COH + IUI (not significant). Cumulative pregnancy rates for COH/IUI in stage I/II were significantly higher than in stage III/IV. Monthly fecundity rates were 3.81% for stage I/II spontaneous, 4.59% for COH/IUI, 3.05% for stage III/IV spontaneous, and 1.68% for COH/IUI (not significant).


COH + IUI did not improve pregnancy rates in any stage of endometriosis. In stage III/IV we recommend postoperative in vitro fertilization.



Qual Life Res. 2014 Mar;23(2):639-43.

Impact of laparoscopic colorectal segment resection on quality of life in women with deep endometriosis: one year follow-up.

Ribeiro PA1Sekula VGAbdalla-Ribeiro HSRodrigues FCAoki TAldrighi JM.




To evaluate the changes in quality of life (QOL) over a 1-year follow-up period in patients submitted to laparoscopic colorectal resection for the treatment of deep endometriosis.


A prospective observational cohort study (Canadian Task Force Design Classification II) involving 40 women with intestinal deep endometriosis was conducted between June 2007 and September 2008 at the Department of Obstetrics and Gynecology, Santa Casa Medical School, Sao Paulo, Brazil. Prior to the surgical procedure, all patients received magnetic resonance studies of the pelvis and rectal echoendoscopy, which suggested intestinal involvement of the disease in all cases. The patients received laparoscopic colorectal resections and treatment for other endometriotic lesions. The subjects completed the QOL SF-36 at 3 time points (T0 pre-operatively; T1 6 months post-operatively; and T2 1 year post-operatively).


The physical functioning, role physical, social functioning and role emotional subscales evidenced the most substantial median increases for T0, T1 and T2. The pain, general health, vitality and mental health domains showed slight changes and increases in medians but did not increase to the same extent as the previous group. Significant improvements were observed in all domains of the SF-36 throughout the study period (p < 0.05). Physical health-related QOL domains showed greater improvement than mental health domains. Analyses of age, parity and body mass index as potential factors influencing the impact of surgery on QOL revealed no differences. Therefore, these factors were not used as prognostic indicators for the surgical procedure or for patient follow-up. In addition, we noted that the patients with poorest results on the initial QOL questionnaire showed the greatest improvements at the end point.


The study results showed that laparoscopic colorectal segment resection for endometriosis had a positive impact on QOL in this patient group. The positive effects persisted 1 year after surgery.




Cochrane Database Syst Rev. 2013 Aug 5;(8)

Antioxidants for female subfertility.

Showell MG1Brown JClarke JHart RJ.




A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This difficulty with conception may affect up to a quarter of all couples planning a child. The reported prevalence of subfertility has increased significantly over the past twenty years. It is estimated that for 40% to 50% of couples, subfertility may be a result of female problems, including ovulatory disorders, poor egg quality, fallopian tube damage and endometriosis. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assessed the evidence for the effectiveness of different antioxidants in female subfertility.


To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women.


We searched the following databases (from inception to April 2013) with no language restrictions applied: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS and OpenSIGLE. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the Trials Registers. Reference lists were checked, and a search on Google was performed.


We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. Trials comparing antioxidants with fertility drugs alone and trials that exclusively included fertile women attending a fertility clinic because of male partner infertility were excluded.


Three review authors independently screened 2127 titles and abstracts, and 67 of these potentially eligible trials were appraised for inclusion and quality through review of full texts and contact with authors. Three review authors were involved in data extraction and assessment of risk of bias. Review authors also collected data on adverse events as reported from the trials. Studies were pooled using fixed-effect models; however, if high heterogeneity was found, a random-effects model was used. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the dichotomous outcomes of live birth, clinical pregnancy and adverse events. Analyses were stratified by type of antioxidant, by indications for subfertility and by those women also undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection techniques (ICSIs). The overall quality of the evidence was assessed by applying GRADE criteria.


A total of 28 trials involving 3548 women were included in this review. Investigators compared oral antioxidants, including combinations of antioxidants, pentoxifylline, N-acetyl-cysteine, melatonin, L-arginine, vitamin E, myo-inositol, vitamin C, vitamin D+calcium and omega-3-polyunsaturated fatty acids with placebo, with no treatment/standard treatment or another antioxidant.Antioxidants were not associated with an increased live birth rate compared with placebo or no treatment/standard treatment (OR 1.25, 95% CI 0.19 to 8.26, P = 0.82, 2 RCTs, 97 women, I(2) = 75%, very low-quality evidence). This suggests that among subfertile women with an expected live birth rate of 37%, the rate among women taking antioxidants would be between 10% and 83%.Antioxidants were not associated with an increased clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.30, 95% CI 0.92 to 1.85, P = 0.14, 13 RCTs, 2441 women, I(2)= 55%, very low-quality evidence). This suggests that among subfertile women with an expected clinical pregnancy rate of 23%, the rate among women taking antioxidants would be between 22% and 36%.Only one trial reported on live birth in the antioxidant versus antioxidant comparison, and two trials reported on clinical pregnancy in this comparison. Only subtotals were used in this analysis, and meta-analysis was not possible as each trial used a different antioxidant.Pentoxifylline was associated with an increased clinical pregnancy rate compared with placebo or no treatment (OR 2.03, 95% CI 1.19 to 3.44, P = 0.009, 3 RCTs, 276 women, I(2) = 0%).Adverse events were reported by 14 trials in the meta-analysis and included miscarriage, multiple pregnancy, ectopic pregnancy and gastrointestinal effects. No evidence revealed a difference in adverse effects between antioxidant groups and control groups, but these data were limited.The overall quality of evidence was ‘very low’ to ‘low’ because of poor reporting of outcomes, the number of small studies included, high risk of bias within studies and heterogeneity in the primary analysis.


The quality of the evidence in the ‘antioxidant versus placebo/no treatment’ and in the ‘antioxidant versus antioxidant’ comparisons was assessed to be ‘very low’. Antioxidants were not associated with an increased live birth rate or clinical pregnancy rate. There was some evidence of an association of pentoxifylline with an increased clinical pregnancy rate; however, there were only three trials included in this comparison. Future trials may change this result. Variation in the types of antioxidants given meant that we could not assess whether one antioxidant was better than another. There did not appear to be any association of antioxidants with adverse effects for women, but data for these outcomes were limited.



Diagn Pathol. 2013 Aug 5;8:131.

Extrauterine adenomyoma of the liver with a focally cellular smooth muscle component occurring in a patient with a history of myomectomy: case report and review of the literature.

Huanwen WHui ZXiaowei XZhaohui L.


Since first reported in 1986, 14 cases of extrauterine adenomyoma have been reported in the English literature, most often occurring in the ovaries. In this report, we present the first case of extrauterine adenomyoma involving the liver in a 29-year-old woman who presented with a 2-year history of low back pain with recent worsening and a history of laparoscopic myomectomy 5 years previously. Gross inspection of the specimen revealed a subcapsular mass that had a well-circumscribed margin with the adjacent liver tissue. By histopathologic examination, the multilobular mass was composed of a smooth muscle component and benign endometrioid glands and stroma. The smooth muscle component was focally cellular, and the endometrioid glands had secretory features. Both the smooth muscle component and endometrioid tissue were positive for ER and PR. The smooth muscle component was also positive for desmin and SMA, while the endometrioid stroma was positive for CD10. Other extrauterine lesions composed of a mixture of smooth muscle tissue and heterotopic endometrioid tissue, including endometriosis with a smooth muscle component, leiomyomatosis/leiomyomas associated with endometriosis and uterus-like masses, should be included in differential diagnoses. The patient was free from recurrence 5 months after liver tumor resection.



BMJ Case Rep. 2013 Aug 5;2013.

Detection and differential diagnosis of suspected malignant transformation of an endometrioma during pregnancy.

Chaudhry S1Glanc PSalem S.



Asymptomatic female in her early 30s presented for her singleton nuchal translucency ultrasound at 12.4 weeks of gestational age. No fetal abnormalities were seen. A large maternal left adnexal mass was identified, prompting a transvaginal ultrasound. The findings were felt to be consistent with an endometrioma, albeit with a 1 cm solid nodule. At this point, the diagnosis was considered to likely represent a decidualised endometrioma; however, warranting careful follow-up. The 20-week anatomy scan demonstrated an enlarging solid nodule that now contained vascularity within the left adnexal mass prompting an MRI. These features were more suggestive of malignancy, although a decidualised endometrioma, which can demonstrate intrapartum growth and vascularity, remained in the differential. Intrapartum sonographic surveillance documented progressive growth. The lesion was uneventfully removed at the time of delivery. Pathology showed clear cell carcinoma within an endometrioma.



Gynecol Endocrinol. 2013 Oct;29(10):883-90.

Oral contraceptive pills for endometriosis after conservative surgery: a systematic review and meta-analysis.

Wu L1Wu QLiu L.



To assess the effects of oral contraceptive pills (OCPs) for endometriosis in women after conservative surgery, we performed a search of PubMed, Embase, ISI Web of Science, Cochrane Library, Scidirect, Chinese VIP, CNKI and WANGFANG database. Randomized controlled trials (RCTs) of OCPs in postoperative medical therapy for endometriosis were collected. Articles published as of January 2013 with no language restriction were identified using defined keywords, and 15 studies comprising 1850 patients were included. There was a significantly higher rate of total endometriosis remission [OR = 2.55, 95% CI (1.68, 3.86), p < 0.00001] and a lower rate of recurrence [OR = 0.31, 95% CI (0.22, 0.45), p < 0.00001] in the OCPs group compared with surgery alone. There appears to be no statistical difference in pregnancy rates between the OCPs group as compared with surgery alone or other hormonal drug treatments in infertility patients. As for the rate of recurrence and complete remission, there were no statistical differences among OCPs and gestrinone, mifepristone or GnRH-a groups. However, OCPs users had less side effects that were more mild as compared with patients using other hormonal treatments.



J Obstet Gynaecol. 2013 Aug;33(6):597-600.

Differences in omega-3 and fatty acid profiles between patients with endometriosis and those with a functional ovarian cyst.

Kim TH1Jo SPark YLee HHChung SHLee WS.



Endometriosis is a chronic inflammatory gynaecological disease. Problems associated with endometriosis include dysmenorrhoea, dyspareunia and infertility. We evaluated the omega-3 and fatty acid profiles in erythrocytes and tissues in patients with endometriosis (n = 10) or a functional ovarian cyst (n = 12), using a food frequency questionnaire that included questions about 117 food items typical of Korean meals. Erythrocyte levels of 20:5n3 and 22:6n3, the omega-3 index, and n-3 PUFA were significantly higher, and the n-6:n-3 ratio was significantly lower in the endometriosis group than in the functional ovarian cyst group. The functional ovarian cyst group consumed significantly more fruit than the group with endometriosis.



Drugs R D. 2013 Sep;13(3):235-9.

Serum concentration of lignocaine after pertubation: an observational study.

Wickström K1Spira JEdelstam G.




The objective of this study was to report the serum concentration of lignocaine after pertubation in patients with endometriosis.


Prospective observational study.


The study was carried out at a gynaecological outpatient unit in Stockholm, Sweden.


Eligible patients had endometriosis with a dysmenorrhoic pain score of >50 mm on a visual analogue scale, and patent fallopian tubes.


Patients with endometriosis (n = 25) were included in the study. The patients received pre-ovulatory pertubations with lignocaine hydrochloride 10 mg (n = 16) or ringer acetate (placebo, n = 9). The procedure comprised passing the study solution through the uterus and the fallopian tubes via an intra-cervical balloon catheter. Serum samples were collected at 0, 5, 15 and 30 min after pertubation.


The serum samples were analysed for the concentration of lignocaine with an LCMS-SIM method.


Low levels of lignocaine were detected in the serum samples following pertubation of 10 mg lignocaine hydrochloride. The highest observed concentration was seen after 30 min (mean 0.050 μg/ml), with an individual maximum of 0.124 μg/ml. Maximum concentration (C max) and time to C max (T max) could not be calculated, since the highest values were observed in the 30-min samples, which was the last sample obtained. Lignocaine was not detected after pertubation with placebo.


The serum levels of lignocaine following pertubation of 10 mg lignocaine hydrochloride are detectable but low. Lignocaine pertubated through the fallopian tubes reaches the peritoneal cavity and diffuses through the peritoneum into the blood circulation. Pertubation with lignocaine is safe and has no lignocaine-related adverse events.



World J Gastroenterol. 2013 Aug 7;19(29):4818-22.

Intrahepatic endometriosis as differential diagnosis: case report and literature review.

Fluegen G1Jankowiak FZacarias Foehrding LKroepil FKnoefel WTTopp SA.



Intrahepatic endometriosis is one of the rarest forms of atypical endometriosis; only eighteen cases have been reported in the English literature. We describe the case of a 32-year-old woman, who presented with persistent, non-cyclical upper right quadrant abdominal pain, a central liver cyst, and no history of endometriosis. Three years previous, she was diagnosed with an intrahepatic cyst. The lesion progressed and two laparoscopic deroofing-operations were performed, yet the diagnosis of intrahepatic endometriosis was never reached. She presented in our clinic with further progress of the cyst as well as obstruction of the intrahepatic biliary system. The magnetic resonance imaging showed a 9.5 cm × 12 cm, lobulated intrahepatic cyst. We performed an ultrasonic pericystectomy. Immunostaining confirmed intrahepatic endometriosis. Only one of the previously described eighteen patients with intrahepatic endometriosis presented with cyclical pain in the upper right abdominal quadrant accompanying menstruation. This lack of a “typical” clinic makes it challenging to diagnose extragonadal endometriosis without histopathology. A previous history of endometriosis was described in only twelve cases, thus the diagnosis of this condition should not be limited to patients with a known history of endometriosis. Six of 18 patients were postmenopausal, demonstrating this condition is not limited to women of reproductive age. A preoperative diagnosis was only reached in seven of the previously described cases, highlighting the importance of preoperative biopsies. Yet due to the potential adverse effects, a transhepatic biopsy must be discussed individually. Although rare, intrahepatic endometriosis should always be considered as a differential diagnosis in women with recurrent hepatic cysts, regardless of age or previous medical history. In such cases, histology is essential and a pericystectomy should be performed as standard of care.



JSLS. 2013 Apr-Jun;17(2):227-34.

Deep infiltrating colorectal endometriosis treated with robotic-assisted rectosigmoidectomy.

Neme RM1Schraibman VOkazaki SMaccapani GChen WJDomit CDKaufmann OGAdvincula AP.




Deep infiltrating pelvic endometriosis with bowel involvement is one of the most aggressive forms of endometriosis. Nowadays, robotic technology and telemanipulation systems represent the latest developments in minimally invasive surgery. The aim of this study is to present our preliminary results and evaluate the feasibility of robotic-assisted laparoscopic colorectal resection for severe endometriosis.


Between September 2009 and December 2011, 10 women with colorectal endometriosis underwent surgery with the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA). We evaluated the following parameters: short-term complications, clinical outcomes and long-term follow-up, pain relief recurrence rate, and fertility outcomes.


Extensive ureterolysis was required in 8 women (80%). Ovarian cystectomy with removal of the cystic wall was performed in 7 women (70%). Torus resection was performed in all women, with unilateral and bilateral uterosacral ligament resection in 1 woman (10%) and 8 women (80%), respectively. In addition to segmental colorectal resection in all cases, partial vaginal resection was necessary in 2 women (20%). An appendectomy was performed in 2 patients (20%). The mean operative time with the robot was 157 minutes (range, 90-190 minutes). The mean hospital stay was 3 days. Six patients had infertility before surgery, with a mean infertility time of 2 years. After a 12-month follow-up period, 4 women (67%) conceived naturally and 2 (33%) underwent in vitro fertilization.


We show that robotic-assisted laparoscopic surgery for the treatment of deep infiltrating bowel endometriosis is feasible, effective, and safe.



Hum Reprod. 2013 Nov;28(11):2972-80.

Individualized decision-making in IVF: calculating the chances of pregnancy.

van Loendersloot LL1van Wely MRepping SBossuyt PMvan der Veen F.




Are we able to develop a model to calculate the chances of pregnancy prior to the start of the first IVF cycle as well as after one or more failed cycles?


Our prediction model enables the accurate individualized calculation of the probability of an ongoing pregnancy with IVF.


To improve counselling, patient selection and clinical decision-making in IVF, a number of prediction models have been developed. These models are of limited use as they were developed before current clinical and laboratory protocols were established.


This was a cohort study. The development set included 2621 cycles in 1326 couples who had been treated with IVF or ICSI between January 2001 and July 2009. The validation set included additional data from 515 cycles in 440 couples treated between August 2009 and April 2011. The outcome of interest was an ongoing pregnancy after transfer of fresh or frozen-thawed embryos from the same stimulated IVF cycle. If a couple became pregnant after an IVF/ICSI cycle, the follow-up was at a gestational age of at least 11 weeks.


Women treated with IVF or ICSI between January 2001 and April 2011 in a university hospital. IVF/ICSI cycles were excluded in the case of oocyte or embryo donation, surgically retrieved spermatozoa, patients positive for human immunodeficiency virus, modified natural IVF and cycles cancelled owing to poor ovarian stimulation, ovarian hyperstimulation syndrome or other unexpected medical or non-medical reasons.


Thirteen variables were included in the final prediction model. For all cycles, these were female age, duration of subfertility, previous ongoing pregnancy, male subfertility, diminished ovarian reserve, endometriosis, basal FSH and number of failed IVF cycles. After the first cycle: fertilization, number of embryos, mean morphological score per Day 3 embryo, presence of 8-cell embryos on Day 3 and presence of morulae on Day 3 were also included. In validation, the model had moderate discriminative capacity (c-statistic 0.68, 95% confidence interval: 0.63-0.73) but calibrated well, with a range from 0.01 to 0.56 in calculated probabilities.


In our study, the outcome of interest was ongoing pregnancy. Live birth may have been a more appropriate outcome, although only 1-2% of all ongoing pregnancies result in late miscarriage or stillbirth. The model was based on data from a single centre.


The IVF model presented here is the first to calculate the chances of an ongoing pregnancy with IVF, both for the first cycle and after any number of failed cycles. The generalizability of the model to other clinics has to be evaluated more extensively in future studies (geographical validation). Centres with higher or lower success rates could use the model, after recalibration, by adjusting the intercept to reflect the IVF success rates in their centre.


This project was funded by the NutsOhra foundation (Grant 1004-179). The NutsOhra foundation had no role in the development of our study, in the collection, analysis and interpretation of data; in writing of the manuscript, and in the decision to submit the manuscript for publication. There were no competing interests.



Int J Clin Exp Pathol. 2013 Jul 15;6(8):1603-9.

In vitro apoptosis effects of GnRHII on endometrial stromal cells from patients with endometriosis.

Huang F1Zou YWang HCao JYin T.




To study the effect of gonadotropin-releasing hormone II (GnRHII) on the cell apoptosis of ectopic, eutopic and normal endometrial stromal cells cultured in vitro from endometriosis patients, and to provide theoretical basis for exploring new treatments for endometriosis (EMs).


Ectopic, eutopic and normal endometrial stromal cells were isolated, cultured and identified in vitro, then treated with different concentrations of GnRHII (0, 10(-10) M, 10(-8) M and 10(-6) M). Cell apoptosis was detected by Hoechst staining and flow cytometry.


GnRHII increased apoptosis in ectopic, eutopic and normal stromal cells in a dosage-dependent manner (P<0.05), and apoptosis of ectopic stroma cells was significantly higher than that of eutopic and normal cells (P<0.05); apoptosis in eutopic and normal cells had no different (P>0.05).


GnRHII can significantly induce apoptosis in ectopic, eutopic and normal endometrial stromal cells from patients with endometriosis, especially to the ectopic.



J Reprod Infertil. 2013 Apr;14(2):50-5.

Investigation of apelin expression in endometriosis.

Ozkan ZS1Cilgin HSimsek MCobanoglu BIlhan N.




Apelin is a mitogenic peptide; it has functions in vessel formation and cell proliferation. In this study we aimed to evaluate the serum and tissue levels and local expression pattern of apelin in eutopic and ectopic endometrium from patients with and without endometriosis and to compare the proliferative and secretory phase differences.


Thirty women with endometriosis and 15 women without endometriosis undergoing surgery for benign indications as control group were included in the study. Serum and tissue concentrations and proliferative and secretory phase expression patterns of apelin were evaluated in the ectopic and eutopic endometrium using immunoassay and immunohistochemistry methods. The results were compared with Mann-Whitney U test. The p-values smaller than 0.05 were considered as statistically significant.


Apelin expression was detected in eutopic and ectopic endometrium of women with endometriosis and endometrium of control group. Intense immunoreactivity of apelin was observed in glandular cells of eutopic and ectopic endometrial tissues of women with endometriosis and endometrium of control group during secretory phase (p<0.01). In both groups, tissue concentrations of apelin were higher than of the serum (p=0.03) but, there were no significant differences between the two groups for tissue and serum concentrations of apelin.


Apelin expression showed cyclic changes in eutopic and ectopic endometrium. Its expression may be related to menstrual changes of angiogenesis in endometrium of women.



Rev Bras Ginecol Obstet. 2013 Jun;35(6):262-7.

Correlation between serum Ca-125 levels and surgical findings in women with symptoms evocative of endometriosis.

[Article in Portuguese]

Zomer MT1Ribeiro RTrippia CHCavalcanti TCHayashi RMKondo W.




To correlate preoperative serum cancer antigen 125 (Ca-125) levels and laparoscopic findings in women with pelvic pain symptoms suggestive of endometriosis.


A retrospective study was conducted including all women with pelvic pain symptoms suspected for endometriosis operated by laparoscopy from January 2010 to March 2013. Patients were divided into 2 groups according to preoperative Ca-125 level (<35 U/mL and ≥ 35 U/mL). Subsequently, patients with ovarian endometriomas were excluded and a further analysis was conducted again according to the preoperative Ca-125 level. The following parameters were compared between groups: presence of ovarian endometrioma, presence and number of deep infiltrating endometriosis (DIE) lesions and American Society for Reproductive Medicine score. The statistical analysis was performed with Statistica version 8.0, using the Fisher exact test, Student’s t-test and Mann-Whitney test, when needed. A p value of <0.05 was considered to be statistically significant.


During the study period, a total of 350 women were submitted to laparoscopic treatment of endometriosis. One hundred thirty patients (37.1%) had Ca-125 ≥ 35 U/mL and 220 (62.9%) had Ca-12<35 U/mL. The presence of ovarian endometriomas (47.7 versus 15.9%), DIE lesions (99.6 versus 78.6%) and intestinal DIE lesions (60 versus 30.9%) was more frequent, and the AFSr score was higher (34 versus 6) in the former group. In the second analysis, excluding the patients with ovarian endometriomas (≥ 35 U/mL=68 patients and <35 U/mL=185 patients), similar results were obtained. The presence of DIE lesions (91.2 versus 76.2%), intestinal DIE lesions (63.2 versus 25.4%), bladder DIE lesions (20.6 versus 4.8%) and ureteral DIE lesions (7.3 versus 1.6%) was more frequent, and the AFSr score was higher (10 versus 6) in the Ca-125 ≥ 35 U/mL group.


Investigation for DIE is mandatory in women with pelvic pain symptoms suggestive of endometriosis with a preoperative Ca-125 level ≥ 35 U/mL, especially when an ovarian endometrioma is not present.



Genesis. 2013 Oct;51(10):734-40.

Genetic inactivation of the allograft inflammatory factor-1 locus.

Casimiro I1Chinnasamy PSibinga NE.



Allograft inflammatory factor-1 (Aif-1) is a 17 kDa EF hand motif-bearing protein expressed primarily in developing spermatids and cells of monocyte/macrophage lineage. Increased Aif-1 expression has been identified in clinically important conditions, including rheumatoid arthritis, systemic sclerosis, endometriosis, and transplant-associated arteriosclerosis. Largely similar gene products arising from the same locus are known as ionized Ca(2+) binding adapter-1 (Iba1), microglial response factor-1 (MRF1), and daintain; Iba1 in particular has emerged as a histologic marker of microglia and their activation in pathologic CNS conditions, including the response to facial nerve axotomy and stroke, uveitis, and experimental autoimmune neuritis and encephalomyelitis. Nevertheless, how aif-1 gene products affect cellular function is only partly understood, and the physiologic significance of these products for male fertility, immune system development, and inflammation has not been described. To permit such investigations, we generated a mouse line with targeted deletion of the coding regions of the aif-1 gene. Here we report that mice lacking Aif-1 breed well and show normal post-natal growth, but show resistance to disease in a model of collagen-induced arthritis. We anticipate that these mice will be useful for studies of Aif-1 function in a variety of immune and inflammatory disease models.



Fertil Steril. 2013 Nov;100(5):e33.

Rectal shaving using PlasmaJet in deep endometriosis of the rectum.

Roman H1.




To report an original technique of rectal shaving using the PlasmaJet system (Plasma Surgical, Inc.) for the management of deep endometriosis of the rectum.


Video demonstration of a new surgical technique.




A 34 year-old primipara with a deep endometriosis involving the vagina and the mid-rectum over 30 mm.


An original technique of rectal shaving.


The procedure is based on the specific properties of PlasmaJet: the lack of lateral thermal spread around the jet of plasma making the dissection on contact of rectal wall safe, the precise ablative property allowing for in situ ablation of rectal endometriosis implants, and the kinetic energy enhancing the dissection of subperitoneal spaces. The steps of the technique and the role of PlasmaJet are emphasized. The surgical technique report using anonymous patients is exempt from ethical approval by the IRB.


The patient’s outcome was uneventful, and colorectal complaints were completely relieved one week after surgery. Since November 2012, we have employed this technique in 18 patients, with only favorable outcomes.


The technique described in this video article may represent a step toward a more complete removal of endometriotic implants and better colorectal outcomes.



Reprod Biomed Online. 2013 Nov;27(5):497-505.

Oestrogen and progesterone action on endometrium: a translational approach to understanding endometrial receptivity.

Young SL1.



Embryo attachment and implantation is critical to successful reproduction of all eutherian mammals, including humans; a better understanding of these processes could lead to improved infertility treatments and novel contraceptive methods. Experience with assisted reproduction, especially oocyte donation cycles, has established that despite the diverse set of hormones produced by the ovary in a cycle-dependent fashion, the sequential actions of only two of them, oestrogen and progesterone, are sufficient to prepare a highly receptive endometrium in humans. Further investigation on the endometrial actions of these two hormones is currently providing significant insight into the implantation process in women, strongly suggesting that an abnormal response to progesterone underlies infertility in some patients.





Int J Womens Health. 2013 Jul 29;5:449-55.

Is a bowel resection necessary for deep endometriosis with rectovaginal or colorectal involvement?

Acién P1Núñez CQuereda FVelasco IValiente MVidal V.




The purpose of this paper is to report the long-term results of surgery without bowel resection in patients suffering from deep infiltrating endometriosis with rectovaginal or colorectal involvement.


This retrospective observational study identified 42 patients suffering with deep infiltrating endometriosis who underwent surgery. Conservative surgery was performed in 23 women (only one of them with bowel resection), and 19 women underwent a hysterectomy and bilateral salpingo-oophorectomy (HBSO). In the conservative surgery group, a later HBSO was performed in eight patients as a second operation. Pregnancies, recurrences, reoperations, use of hormone replacement therapy, and outcomes during long-term follow-up were analyzed.


The average follow-up duration was 7 ± 5.7 years in conservative surgery cases. Only one patient was treated with sigmoid bowel resection in 1997 and had complications. In this conservative surgery group, 13 patients (56%) received medical treatment after surgery, 10 patients wanted to get pregnant (of whom seven [70%] were successful), and eight patients underwent a subsequent HBSO because of recurrent symptoms and/or endometrioma. Therefore, HBSO was performed in 27 patients, of whom 14 (51.8%) used hormone replacement therapy for 5.6 ± 3.6 years. No recurrences or complications were observed in patients after HBSO with or without hormone replacement therapy.


Good clinical results can be obtained by performing only conservative surgery and/or HBSO without bowel resection, an alternative that could reduce the number of colorectal resections that are performed very frequently nowadays. After HBSO, patients may use hormone replacement therapy for several years with total satisfaction and well-being.




Int J Med Sci. 2013 Jul 30;10(9):1199-208.

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis.

Yeo SG1Won YSLee HYKim YILee JWPark DC.




Endometriosis is characterized by repeated inflammatory changes and serious adhesions, inducing innate and adaptive immune responses within the abdominal cavity. To assess these immune responses, we evaluated the levels of expression of Toll-like receptors (TLR)-1, -2, -4, -5, and -9; nucleotide-binding oligomerization domains (NOD)-1 and -2; interleukins-1β, -6, -8, -10, and -12; interferon-γ; tumor necrosis factor-α; inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS); and immunoglobulins (Igs) in patients with endometriosis.


The levels of TLRs, NODs, cytokines, and NOS mRNAs in peritoneal effusions were assessed by real time reverse transcription-polymerase chain reaction; and IgG, IgA and IgM concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in 40 patients with and 40 without endometriosis. Findings from the two groups were compared.


We observed expression of all pattern recognition receptors (PRRs), cytokines, and NOS mRNAs and Igs in the effusion fluid of patients with and without endometriosis. The levels of TLR-2 and -9; NOD-1 and -2; iNOS and eNOS mRNAs and CA 125 were significantly higher in the endometriosis than in the non-endometriosis group (p<0.05 each). Moreover, PRR, cytokine, and NOS expression showed significant correlations (p<0.05).


PRRs, cytokines, and NOS, which act cooperatively in the innate immune response, are closely associated with endometriosis. Increased expression of TLR-2, TLR -9, NOD-1, NOD-2, and NOS mRNA in peritoneal fluid may be associated with endometriosis.



Int J Clin Exp Med. 2013 Aug 1;6(7):583-8.

The incidence and characteristics of uterine bleeding during postoperative GnRH agonist treatment combined with estrogen-progestogen add-back therapy in endometriosis patients of reproductive age.

Han Y1Zou SELong QQZhang SF.



To evaluate the incidence and characteristics of uterine bleeding during postoperative gonadotropin-releasing hormone agonist (GnRHa) treatment combined with the lowest effective dose of estrogen-progestogen add-back therapy in Chinese women of reproductive age with endometriosis. Seventy Chinese women aged 18 to 50 years with stage III or IV endometriosis and treated with postoperative GnRHa after conservative surgery for endometriosis were eligible for this study. Patients were randomly divided into two equal groups, G and A. Group G (n = 35) received three 28-day cycles of postoperative GnRHa treatment by subcutaneous injection (goserelin, 3.6 mg). Group A (n = 35) received the same GnRHa treatment in addition to daily estradiol valerate (0.5 mg) and dydrogesterone (5 mg) add-back therapy. Serum E2 and FSH levels were assessed at the end of each treatment cycle, as well as incidence and patterns of uterine bleeding. After the last GnRHa treatment cycle, endometrial thickness was evaluated by ultrasonography and the recovery of menstruation was recorded. Uterine bleeding incidence was above 90% in both groups during the first treatment cycle (group G: 90.6%; group A: 93.8%), but decreased markedly in the second treatment cycle (group G: 15.6%; group A: 21.9%), and continued to decline until the end of the third treatment cycle (group G: 6.3%; group A: 12.5%). For each cycle, the incidence of uterine bleeding in group A was slightly but not statistically higher. Irregular spotting was the most common uterine bleeding pattern observed in each of the three treatment cycle. The addition of estrogen and progestogen therapy to a postoperative GnRHa regimen does not lead to an increase in the duration or amount of treatment-induced uterine bleeding.



J Med Assoc Thai. 2013 Feb;96(2):140-3.

Cumulative recurrence rates of endometriosis-associated pain after long-term intramuscular depot medroxyprogesterone acetate therapy.

Cheewadhanaraks S1.




To determine the cumulative recurrence rates of endometriosis-associated pain after long-term intramuscular depot medroxyprogesterone acetate (DMPA) therapy.


Sixty-one patients with symptomatic endometriosis, who had been treated with DMPA for 15 months and were satisfied with the treatment, were included in the present study. Telephone questionnaires were used to collect information including pain recurrence. Medical records were reviewed to obtain more information. Estimates of cumulative recurrence rates of pain were calculated using the Kaplan-Meier technique and estimates of risk were computed using the Cox proportional hazards models.


The cumulative recurrence rates of pain after DMPA treatment were 18%, 28%, 41%, 46%, and 50% at months 12, 24, 36, 48, and 60, respectively. Age > 30 years (hazard ratio = 4.40 [95% CI, 1.45-13.37]; p = 0.009), moderate to severe stages of endometriosis (3.02 [1.30-7.03]; p = 0.010), and severe pain prior to treatment (7.80 [1.02-59.61]; p = 0.048) were found to be independent risk factors for the recurrence of pain.


Half of the patients had recurrent pain five years after DMPA treatment ended.



Eur J Obstet Gynecol Reprod Biol. 2013 Oct;170(2):533-8.

A retrospective review of patient-reported outcomes on the impact on quality of life in patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis.

Tan BK1Maillou KMathur RSPrentice A.




The Endometriosis Health Profile-30 (EHP-30), an endometriosis-specific health-related quality of life (HRQoL) questionnaire, forms part of our service evaluation of all women undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis in our reproductive medicine unit. We used the EHP-30 to investigate patient-reported outcomes in all patients undergoing this procedure.


Retrospective review of 16 women with endometriosis undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for debilitating symptoms after other modalities of treatment had failed. Patients completed EHP-30 questionnaires before the operation and again three months after surgery.


Total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis results in a significant improvement in HRQoL. The impact was greatest in the core domains–control and powerlessness, emotional wellbeing and social support. There was a 100% response rate for the core domains whereas in the modular domains, missing response rates ranged from 12.5% to 62.5%, with the percentage of missing data being greatest in the concern on infertility and relationship with children domains. Pain was significantly positively correlated with control and powerlessness, emotional wellbeing, work life and relationship with children. After multiple regression analyses, only control and powerlessness and emotional wellbeing were found to be predictive of pain. Additionally, changes in pain before and after total abdominal hysterectomy and bilateral salpingo-oophorectomy were significantly positively correlated with the changes in the core domains–control and powerlessness, emotional wellbeing and self image. After multiple regression analyses, change in pain was found to be predictive of ΔControl and powerlessness in our study subjects.


Total abdominal hysterectomy and bilateral salpingo-oophorectomy significantly improves HRQoL in patients debilitated by symptoms attributable to endometriosis and in whom other modalities of treatment have failed.



Curr Opin Oncol. 2013 Sep;25(5):553-7.

Clear cell cancer of the ovary.

Penson RT1Dizon DSBirrer MJ.




Recent discoveries have demonstrated that ovarian cancer is actually composed of multiple separate diseases. Clear cell cancer is an important example. This review will describe the unique biology of clear cell carcinoma, its novel molecular features, and the recent translation of this into new therapeutic approaches.


Clear cell cancer of the ovary is now recognized as a unique disease. Recent work has shown that a subset of clear cell cancers evolve from endometriosis. The oxidative stress conditions found within endometriotic lesions are likely to contribute to the transformation process. Molecular alterations within clear cell cancers include unique cytokine expression patterns and c-met amplification. Clear cell-specific clinical trials based upon these biologic discoveries have been designed and are presently active.


These studies provide substantive support for a unique clinical management of clear cell cancer of the ovary. Future research will exploit the molecular pathways identified in these tumors in an effort to provide more effective therapies. Presently, agents that target angiogenesis or cellular metabolism would be reasonable therapeutic approaches to these tumors.



J Obstet Gynaecol Res. 2014 Jan;40(1):40-5.

Individualized management of umbilical endometriosis: a report of seven cases.

Saito A1Koga KOsuga YHarada MTakemura YYoshimura KYano TKozuma S.




The aim of this study was to review diagnostic/therapeutic strategies of umbilical endometriosis managed in our department and evaluate the effectiveness of these strategies.


Medical records for patients with diagnosis of endometriosis managed from 1999 through 2011 in the University of Tokyo Hospital were retrospectively reviewed. Cases with diagnosis of umbilical endometriosis were identified. Clinical information of age, gravida, parity, histories of surgery and oral contraceptive (OC), management for the disease prior to the first visit, symptoms, patients’ desire for pregnancy, diagnostic/therapeutic methods and prognosis were reviewed and summarized.


During the period, 2530 patients with diagnosis of endometriosis were identified. Seven patients had diagnosis of umbilical endometriosis, giving an incidence of 0.29% of all endometriosis cases and 5.6% of extragenital endometriosis cases. A definitive diagnosis was made by histological examination following a biopsy (two cases) or a resection (three cases). A clinical diagnosis was made by empirical treatment with OC (one case) or dienogest (one case). With regard to therapy, three patients chose expectant management and did not require therapeutic intervention. Three patients began OC and symptoms were well controlled in all patients. One patient who wished to conceive chose a wide resection followed by umbilical reconstruction. She became pregnant afterwards and recurrence was not reported.


There are various options of diagnostic/therapeutic strategies, such as empirical treatments and OC that can provide individualized management of umbilical endometriosis, congruent with the severity of patient symptoms, age and desire for pregnancy.



Reprod Biol Endocrinol. 2013 Aug 15;11:78.

MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis.

Laudanski P1Charkiewicz RKuzmicki MSzamatowicz JCharkiewicz ANiklinski J.


Erratum in



The eutopic endometrium of women with endometriosis, compared with disease-free individuals, contains certain molecular alterations, including the differential expression of microRNA (miRNA). The aim of the study was to compare the expression of the most relevant miRNAs in the eutopic endometrium of women with and without ovarian endometriosis.


A total of 46 regularly menstruating patients, 21 patients with ovarian endometriosis and 25 controls, underwent surgery in the proliferative phase of the cycle. The eutopic endometrium was collected through aspirating biopsy prior to laparoscopy. Only patients with advanced (stage III and IV) histopathologically confirmed ovarian endometriosis were included. TaqMan MicroRNA Array Cards were applied to examine the expression of 667 human miRNAs in 10 patients with endometriosis and 10 controls. Custom-made, low-density real-time PCR arrays were used to confirm the expression of 15 selected molecules in 21 endometriosis patients and 25 disease-free individuals.


Of 667 miRNAs, 2 were highly likely to be upregulated and 13 were downregulated in the eutopic endometrium of patients with endometriosis compared with the controls. Validation using real-time PCR showed that hsa-miR-483-5p (p = 0.012) and hsa-miR-629* (p = 0.02) are significantly downregulated in patients with endometriosis.


Changes in the expression of select miRNAs might lead to or be a consequence of an early defect in the physiological activity of the proliferative endometrium, ultimately resulting in the overgrowth of this tissue outside the uterus.




Hinyokika Kiyo. 2013 Jul;59(7):431-4.

Ureteral endometriosis treated by hormonal therapy : a case report.

Mikami J1Yamamoto HOkamoto AIshimura HImai AHatakeyama SYoneyama THashimoto YKoie TOhyama C.



A 40-year-old woman visited our hospital with asymptomatic macroscopic hematuria. A nonpapillary ureteral tumor protruding from the left orifice was identified by cystoscopy. Computed tomography revealed left hydronephrosis due to the ureteral tumor. Transurethral resection for the ureteral tumor was performed and histopathological examination for the specimen revealed intrinsic type ureteral endometriosis. Administration of luteinizing hormone-releasing hormone agonist for 6 months markedly improved the hydronephrosis. The patient received hormonal therapy for 2 years in total. At present, there is no evidence of disease recurrence 6 months after the termination of hormonal therapy. To our knowledge, the present case was the 14th Japanese case with intrinsic type ureteral endometriosis reported in the literature.



World J Gastroenterol. 2013 Aug 14;19(30):5021-4.

Mucocele of the appendix due to endometriosis: a rare case report.

Tsuda M1Yamashita YAzuma SAkamatsu TSeta TUrai SUenoyama YDeguchi YOno KChiba T.



Mucocele of the appendix due to endometriosis is extremely rare, and there are only 10 previously reported cases in the English literature. We report a case of mucocele of the appendix due to endometriosis and provide the first review of the literature. A 43-year-old woman was admitted to the hospital because of recurrent right lower abdominal pain during her menstrual periods. Colonoscopy revealed submucosal tumor-like elevations of the appendiceal orifice. Computed tomography and magnetic resonance imaging of the abdomen suggested cystic lesions near the appendix. Consequently, mucocele of the appendix was suspected preoperatively. An open ileocecal resection was performed. Multiple cystic lesions were observed around the appendix. The cystic lesions contained mucus. Histopathological examination was consistent with a mucocele of the appendix due to endometriosis. The postoperative course was uneventful. We present the first review of the literature to clarify the clinical features.



Gynecol Endocrinol. 2013 Nov;29(11):974-7.

Association study of the TNF-α -1031T/C and VEGF +450G/C polymorphisms with susceptibility to endometriosis.

Saliminejad K1Memariani TArdekani AMKamali KEdalatkhah HPahlevanzadeh ZKhorram Khorshid HR.



Tumor necrosis factor-α (TNF-α), a multifunctional proinflammatory cytokine, and vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, have been investigated in endometriosis patients of different populations. This study was carried out to investigate whether the two polymorphisms, TNF-α -1031T/C and VEGF +450G/C are associated with susceptibility to endometriosis in an Iranian population. Totally, 135 women with diagnosis of endometriosis and 173 women with no evidence of the disease were included in this study. The -1031T/C and +450G/C polymorphisms were assessed by PCR-RFLP analysis, using the two restriction enzymes BbsI and BsmFI, respectively. The frequencies of the TNF-α -1031TC genotype (p = 0.038) and the -1031 C allele (p = 0.048) were significantly lower in patients than control group. In contrast, no significant differences in the genotype and allele frequencies of the VEGF +450G/C polymorphism were found between the case and control groups. Our results suggest that the TNF-α -1031T/C polymorphism was associated with susceptibility to endometriosis in Iranian population, and the -1301C allele may have a protective role in development of endometriosis; On the contrary, we find no association between the VEGF +450G/C polymorphism and risk of endometriosis.



Fertil Steril. 2013 Nov;100(5):1337-42.

Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: a prospective cohort study.

Vlahos N1Vlachos ATriantafyllidou OVitoratos NCreatsas G.




To evaluate the efficacy of continuous oral contraceptive (OC) use versus the usual cyclic fashion in the recurrence of endometriosis-related symptoms after surgery.


Prospective cohort trial involving patients in two tertiary care units.


Academic institution in collaboration with a private hospital.


356 patients underwent surgical treatment by laparoscopy for symptomatic endometriosis.


After surgical treatment for endometriosis, patients offered 6-month course of cyclic OC (including a 7-day pill-free period) or continuous OC.


Recurrence rate of endometriosis-related symptoms and endometriomas after fertility-sparing surgery.


Out of 356 patients, 167 were placed on the usual cyclic OC course and 85 on continuous OC for a minimum of 6 months. The continuous OC group experienced a statistically significant reduction in recurrence rates for endometrioma, dysmenorrhea, and non-menstrual pelvic pain as compared with the cyclic OC group. There was no reduction in the recurrence of dyspareunia between the two groups.


After surgical treatment of endometriosis, the use of both cyclic and continuous OC improves pain symptoms when compared with preoperative scores. Continuous OC appears to be associated with a reduced recurrence rate for dysmenorrhea, non-menstrual pelvic pain, and endometrioma but not for dyspareunia as compared with cyclic OC.



Fertil Steril. 2013 Nov;100(5):1436-43.

Developmental exposure of fetal ovaries and fetal germ cells to endometriosisin an endometriosis model causes differential gene expression in the preimplantation embryos of the first-generation and second-generation embryos.

Birt JA1Taylor KHDavis JWSharpe-Timms KL.




To characterize multigenerational gene expression anomalies in eight-cell stage embryos associated with developmental exposure to endometriosis.


Using an endometriosis model in rats (F0 founder generation) to evaluate gene expression in F1 (fetal exposure) and F2 (fetal germ cell exposure) generation eight-cell stage embryos.




Endometriosis model in rats (Endo) and controls (Sham).


F0 Endo and Sham rats were bred; half the pregnant rats were killed on gestational day 3 to collect F1 eight-cell stage embryos and the others gestated to term (F1 females). Adult F1 females bred; F2 eight-cell embryos collected.


Maintenance of differential gene expression in F1 and F2 generation eight-cell embryos in endometriosis.


Developmental exposure to endometriosis altered the gene signaling pathways, with changes found in apoptosis, the cell cycle process, the response to oxidative stress, negative regulation of molecular function, and RNA processing. The apoptotic genes Diablo, Casp3, Parp1, Cad, and Dnaja3 were increased and the Nfkbia transcripts were decreased in F1 Endo versus F1 Sham embryos. In F2 Endo versus Sham embryos, Casp3 and Cad were statistically significantly increased, and Parp1 and Nfkbia tended to be elevated.


Fetal and germ cell exposure to endometriosis alters apoptotic gene expression in first- and second-generation eight-cell stage embryos, supporting the hypothesis of multigenerational inheritance resulting from exposure to endometriosis in utero.




Am J Epidemiol. 2013 Oct 15;178(8):1219-25.

History of infertility and risk of gestational diabetes mellitus: a prospective analysis of 40,773 pregnancies.

Tobias DKChavarro JEWilliams MABuck Louis GMHu FBRich-Edwards JMissmer SAZhang C.



Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses’ Health Study II cohort (1989-2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)(2)), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations.



ISRN Obstet Gynecol. 2013 Jul 17;2013:242149.

Endometriosis: a disease that remains enigmatic.

Acién P1Velasco I.



Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%-10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease.



Case Rep Obstet Gynecol. 2013;2013:238156.

Abscessed uterine and extrauterine adenomyomas with uterus-like features in a 56-year-old woman.

Bulut AS1Sipahi TU.



Adenomyosis, also known as endometriosis interna, is the presence of endometrial glands and stroma within the myometrium. Its localised form is called adenomyoma and mimics a leiomyoma. Rarely, adenomyomas are located outside the uterus and some of them form uterus-like masses with a thick muscle wall and an endometrium-lined central cavity. They are generally located in the ovary or broad ligament, and, although they are closely related to endometriosis, their pathogenetic mechanisms are different from each other. Müllerian duct fusion defect and subcoelomic mesenchyme transformation theory are two possible pathogenetic mechanisms for this rare entity. Here we report abscessed uterine and extrauterine adenomyomas forming uterus-like masses in the left and right broad ligament and an ectopic adrenal tissue in the left paraovarian region in a 56-year-old woman. Although there is a reported abscessed adenomyosis in the literature, this is the first abscessed extrauterine uterus-like masses with synchronous pelvic pathologies like endometriosis, leiomyomas, adenomyosis, an endometrial polyp, an endocervical polyp, and an ectopic adrenal tissue. This benign lesion gives the impression of leiomyoma, a uterine malformation, or even malignancy preoperatively. Frozen section helps in differential diagnosis.



J Hematol Oncol. 2013 Aug 19;6:60.

PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy.

Wang Y1Wang YLi JYuan ZYuan BZhang TCragun JMKong BZheng W.




Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy.


Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n=96), metastatic cancers (n=22), and benign controls (n=50).


Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n=4) and the metastasis from gastrointestinal tract (n=17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n=4) and endometriosis (n=1), 25 PAX8-/Calretinin+cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia.


PAX8 identifies all Müllerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.



BMJ Case Rep. 2013 Aug 19;2013.

Endometriosis of extra-pelvic round ligament, a diagnostic dilemma for physicians.

Prabhu R1Krishna SShenoy RThangavelu S.



A 49-year-old multiparous woman presented with a swelling in the left groin of 6 months duration. The swelling was associated with a dull aching pain. The patient reported increase in size of the swelling during lifting of heavy weights. Menstrual history was normal and there was no increase in pain over the swelling during menstruation. She underwent a caesarean section 20 years ago and the scar had healed by primary intention. She was provisionally diagnosed to have a left-sided inguinal hernia. Ultrasonography showed a multiloculated cyst measuring 5.3×1.5×5.2 cm within the inguinal canal. The patient had excision of the cyst under spinal anaesthesia. Intraoperatively the cyst was found to arise from the left round ligament. It measured 7×6 cm extending to the left lateral vaginal wall. Histopathology revealed endometriosis of the round ligament. Her gynaecological assessment was normal and they recommended no further treatment. On follow-up the patient was asymptomatic and wound had healed well.



J Minim Invasive Gynecol. 2014 Jan-Feb;21(1):55-63.

Cellular, histologic, and molecular changes associated with endometriosisand ovarian cancer.

Siufi Neto J1Kho RM2Siufi DF3Baracat EC4Anderson KS5Abrão MS4.



Our understanding of the pathogenesis of endometriosis is rapidly evolving as early molecular events are increasingly identified. Endometriosis is associated with increased risk of ovarian cancer and exhibits neoplastic phenotypes including invasion of stromal tissue and lymphatic spread to distant organs. This review of the literature establishes the clinical, epidemiologic, and pathologic correlation between endometriosis and low-grade ovarian cancer. Genetic studies have demonstrated that endometriotic lesions have mutations in genes directly related to neoplasms, in particular the p53, KRAS, PTEN, and ARID1A genes, which suggests a direct transition from a subset of endometriotic lesions to invasive carcinomas. The identification of both genetic and epigenetic biomarkers including microRNAs are essential for identifying patients at risk for the transition to neoplasia.



J Chin Med Assoc. 2013 Nov;76(11):629-34.

Ovarian cancers arising from endometriosis: a microenvironmental biomarker study including ER, HNF1ß, p53, PTEN, BAF250a, and COX-2.

Lai CR1Hsu CYChen YJYen MSChao KCLi AF.




The microenvironmental biomarkers of different subtypes of ovarian cancers arising from endometriosis have not been studied in Taiwan. Their expression can help in understanding the carcinogenic mechanism.


Our study used immunohistochemistry to compare the expression of estrogen receptor (ER), hepatocyte nuclear factor-1 beta (HNF1ß), p53, phosphatase and tensin homolog (PTEN), BAF250a, and cyclooxygenase-2 (COX-2) among 79 cases of endometriosis-associated ovarian cancers, including 40 (50%) clear cell carcinomas (CCCs), 33 (41%) endometrioid (EM) adenocarcinomas, four (5%) serous carcinomas, one adenosquamous carcinoma, and one adenosarcoma.


Positive stainings for ER, HNF1ß, p53, and COX-2 were identified in 34 (43%), 30 (38%), 10 (13%), and 44 (56%) cases. Loss of PTEN and BAF250a were noted in 29 (37%) and 37 (47%) cases. The expression of ER was reversely correlated with that of HNF1ß (rho = -0.417, p < 0.001) and correlated with p53 (rho = 0.284, p = 0.011). ER positivity was commonly identified in EM adenocarcinomas (91%), and rarely in CCCs (8%) and serous carcinoma (0%; p < 0.001). By contrast, HNF1ß expression was frequently noted in CCCs (65%) and serous carcinomas (50%), but less in EM adenocarcinoma (6%; p < 0.001). All staining results were similar between atypical endometriosis glandular epithelium and contiguous malignant parts. Only nine cases showed 10 minor differences (10/474, 2%) in ER, HNF1ß, and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no difference between the invasive and precursor parts.


Our results supported the suggestion that estrogen-dependent ovarian cancer arising from endometriosis is substantially more associated with EM adenocarcinoma than CCCs. The positive HNF1ß staining was a frequent finding in CCCs, but not in EM adenocarcinoma. The similar staining patterns of atypical endometriosis glandular cells with the invasive parts confirmed their precursor status.



Cesk Patol. 2013 Jun;49(3):134-6.

Endometriosis in a mesothelial cyst of tunica vaginalis of the testis. Report of a case.

Zámečník M1Hoštáková D.



A rare case of endometriosis occurring in paratesticular mesothelial cyst is presented. It was found in a 7 mm mesothelial inclusion cyst of tunica vaginalis in a 46-years-old old man who underwent a radical orchiectomy for seminoma. It showed a typical histologic pattern with endometrioid cylindrical epithelium and cellular stroma. The lesion was immunohistochemically positive for estrogen receptors and progesterone receptors, in contrast with the adjacent mesothelium. However, rare endometrioid epithelial cells expressed mesothelial markers calretinin and cytokeratin 5/6. This immunohistochemical overlap with mesothelium and morphological transition between endometrioid epithelium and mesothelium favor metaplastic pathogenesis of the lesion. In differential diagnosis, it is important to distinguish paratesticular endometriosis from tissue of teratoma (especially when a germ cell tumor is present in the testis, as was seen in this case).



Histol Histopathol. 2014 Sep;29(9):1129-33.

Anti-apoptotic activity in deep pelvic endometriosis.

Abdalla Ribeiro HS1Galvāo MA2Aoki T3Aldrighi JM1Ribeiro PA4.



Since endometriosis is a proliferative disease we evaluated the presence of anti-apoptotic factor (Bcl-2) and pro-apoptotic factor (Bax) in deep pelvic endometriosis. A Cross-sectional observational study was performed at Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. Forty women aged 26 to 46 years with deep endometriosis were selected. They had not been clinically treated for at least 3 months prior to surgery and then underwent surgical laparoscopy to treat the disease. During the surgery, tissue was collected from the uterosacral ligaments and the rectosigmoid; an endometrial biopsy was also performed as a control. All interventions were performed by the same surgeon. The specimens were sent for pathological and immunohistochemical analyses; endometriosis was confirmed in all patients. After the immunohistochemical reaction a semi-quantitative evaluation of the staining intensity (relative optical density-ROD) was conducted, applying the digital densitometric analysis system. In the uterosacral ligaments 97.5% of the specimens were positive for Bcl2 whereas in the rectosigmoid 100% were positive. In the endometrium we observed that 87.5% were positive for Bcl2. BAX expression was null in the rectosigmoid and in the endometrium. In the uterosacral ligaments 2.5% of the specimens expressed BAX. The relative optical density of Bcl2 was higher in the rectosigmoid and in the uterosacral ligament when compared to the endometrium, 0.141±0.002; 0.129±0.001, respectively (p<0.01). We concluded that the anti-apoptotic factor Bcl-2 was expressed in all studied specimens, but in a higher staining intensity in the rectosigmoid and in the uterossacral ligaments in comparison to the endometrium. The pro-apoptotic factor Bax had virtually no expression in the studied tissues.



Front Endocrinol (Lausanne). 2013 Aug 7;4:92.

Shift work and circadian dysregulation of reproduction.

Gamble KL1Resuehr DJohnson CH.



Health impairments, including reproductive issues, are associated with working nights or rotating shifts. For example, shift work has been associated with an increased risk of irregular menstrual cycles, endometriosis, infertility, miscarriage, low birth weight or pre-term delivery, and reduced incidence of breastfeeding. Based on what is known about circadian regulation of endocrine rhythms in rodents (and much less in humans), the circadian clock is an integral regulatory part of the reproductive system. When this 24-h program is disordered by environmental perturbation (such as shift work) or genetic alterations, the endocrine system can be impaired. The purpose of this review is to explore the hypothesis that misalignment of reproductive hormones with the environmental light-dark cycle and/or sleep-wake rhythms can disrupt menstrual cycles, pregnancy, and parturition. We highlight the role of the circadian clock in regulating human reproductive physiology and shift work-induced pathology within each step of the reproductive axis while exploring potential mechanisms from the animal model literature. In addition to documenting the reproductive hazards of shift work, we also point out important gaps in our knowledge as critical areas for future investigation. For example, future studies should examine whether forced desynchronization disrupts gonadotropin secretion rhythms and whether there are sleep/wake schedules that are better or worse for the adaptation of the reproductive system to shift work. These studies are necessary in order to define not only whether or not shift work-induced circadian misalignment impairs reproductive capacity, but also to identify strategies for the future that can minimize this desynchronization.



Eur J Gynaecol Oncol. 2013;34(3):254-6.

Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new markers for endometriosis?

Capobianco G1Wenger JMMarras VCosmi EAmbrosini GDessole MCherchi PL.




Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS).


To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis.


Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis.


Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosisdiagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case.


Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.



Anal Biochem. 2013 Dec 1;443(1):58-65.

Enhancement of ovarian tumor classification by improved reproducibility in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of serum glycans.

Park CW1Jo YJo EJ.



The serum N-glycome is a promising source of biomarker discovery. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of serum N-glycans was attempted for differentiating borderline ovarian tumor from benign cases, for which a low data spread is essential. An experimental protocol using matrix-prespotted MALDI plates and fast vacuum drying of the loaded N-glycan samples was developed, thereby minimizing the intensity variations in the replicates to an average relative standard deviation (RSD) of 3.96% for the highest N-glycan peak (m/z 1485.53) of the Sigma-Aldrich serum standard. When applied to sera of ovarian tumors, this procedure exhibited an average RSD of 5.74% for m/z 1485.53 and of 7.28% for all MS peaks. This improved reproducibility combined with the OVA-Beyond(®) screening software resulted in 75.1% and 79.4% correct classification for benign and borderline tumor samples, respectively, while the classification rates by the conventional ovarian tumor marker CA-125 were 54.4% and 53.1%, respectively. Both true positive rate and true negative rate fluctuated with small numbers of markers and converged as the number of markers increased. Cross-validations were performed in comparison with CA-125. These results suggest that our optimized process for MALDI-TOF MS of the serum glycome has a great potential for the screening of early stage ovarian cancer.




J Minim Invasive Gynecol. 2014 Jan-Feb;21(1):136-41.

Double circular stapler technique for bowel resection in rectosigmoid endometriosis.

Oliveira MA1Crispi CP2Oliveira FM2Junior PS3Raymundo TS2Pereira TD3.



To reduce bladder function impairment and avert the serious complications of anastomotic leakage after segmental rectosigmoidectomy and to minimize the persistence of endometriotic lesions associated with discoid resection, we used the double circular stapling (DCS) technique. This technique enables excision of bowel endometriosis nodules larger than those that can be removed with the single-load technique of the circular stapler. Of 120 patients who underwent surgery to treat bowel endometriosis, intestinal shaving was performed in 24, discoid resection with single circular stapling in 40, and rectosigmoidectomy in 55. Eleven patients (9.2%) underwent the DCS technique. In the DCS group, the size of the rectosigmoid lesion ranged from 2.2 cm to 4.2 cm. Median operative time for the DCS technique was 100 minutes, compared with 150 minutes for rectosigmoidectomy (p = .04). Only 1 of 11 patients (9%) had urinary retention, compared with postoperative urinary retention in 14 of 55 patients (25%) who had undergone rectosigmoidectomy (difference not significant). Only 1 patient, with a 4.2-cm nodule, had a positive margin in the specimen obtained at the second stapling. DCS is a promising technique and may avert rectosigmoidectomy in selected patients.



Obstet Gynecol. 2013 Aug;122(2 Pt 1):233-41.

Nationwide trends in the performance of inpatient hysterectomy in the United States.

Wright JD1Herzog TJTsui JAnanth CVLewin SNLu YSNeugut AIHershman DL.




To examine the use of inpatient hysterectomy and explore changes in the use of various routes of hysterectomy and patterns of referral.


The Nationwide Inpatient Sample was used to identify all women aged 18 years or older who underwent inpatient hysterectomy between 1998 and 2010. Weighted estimates of national trends were calculated and the number of procedures performed estimated. Trends in hospital volume and across hospital characteristics were examined.


After weighting, we identified a total 7,438,452 women who underwent inpatient hysterectomy between 1998 and 2010. The number of hysterectomies performed annually rose from 543,812 in 1998 to a peak of 681,234 in 2002; it then declined consistently annually and reached 433,621 cases in 2010. Overall, 247,973 (36.4%) fewer hysterectomies were performed in 2010 compared with 2002. From 2002 to 2010 the number of hysterectomies performed for each of the following indications declined: leiomyoma (-47.6%), abnormal bleeding (-28.9%), benign ovarian mass (-63.1%), endometriosis (-65.3%), and pelvic organ prolapse (-39.4%). The median hospital case volume decreased from 83 procedures per year in 2002 to 50 cases per year in 2010 (P<.001).


The number of inpatient hysterectomies performed in the United States has declined substantially over the past decade. The median number of hysterectomies per hospital has declined likewise by more than 40%.





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